Spotters in Pediatrics

Spotters in Pediatrics

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Spotters in Pediatrics Editor-in-Chief Anoop Verma

MD FIAP FIAMS

Swapnil Nursing Home and Research Center Civil Lines Raipur, CG 492001

Chapter Editors Navneet Jain MS

Neurology Sanjay Sharma DM (PGI Chandigarh) Consultant Neurologist Modern Medical Institute, Lalpur, Raipur, CG

Laparoscopy Surgeon Ramkinker Medical Institute Purani Basti, Raipur, CG

Neonatology Ramesh Bhatt MD

Infectious Diseases Ashok Gupta MD FIAP

Associate Professor Dept. of Pediatrics, KMC, Manipal

Associate Professor Pediatrics SMS Medical College, Jaipur

Pediatric Surgery Pulak Parag MS MCh (CMC Vellore)

Dermatology Arun Agrawal MD FIAP FIAMS

Pediatric Surgeon Consultant Pediatric Surgeon, Raipur, CG

Chandra Laxmi Hospital Ghaziabad, UP

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Spotters in Pediatrics © 2008 Anoop Verma All rights reserved. No part of this publication should be reproduced, stored in a retrieval system, or transmitted in any form or by any means: electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the editor and the publisher. This book has been published in good faith that the material provided by contributors is original. Every effort is made to ensure accuracy of material, but the publisher, printer and editor will not be held responsible for any inadvertent error(s). In case of any dispute, all legal matters are to be settled under Delhi jurisdiction only.

First Edition : 2008 ISBN : 978-81-8448-249-2

Typeset at Printed at

JPBMP typesetting unit Replica Press

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To My grandfather late Dr GP Shrivastava, MRCP, DTMH, from whom I imbibed the interest in clinical medicine and zeal to remain updated in officepractice. My father late Dr BBL Verma and mother late Suman Lata Verma from whom I learned to aim high and follow the path of voice within. My wife Rashmi, daughter Swapnil and son Shantanu and my whole family are my energy pillars, and my confidence

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Contributors Agrawal Anju Department of Pediatrics UCMS and GTB Hospital Shahdara, Delhi Agrawal Arun, MD FIAP Chandra Laxmi Hospital Ghaziabad, UP Agrawal Ashwani, DCH Pediatrician and Neonatologist Gudhiari, Raipur, CG Agrawal Sanjay, MD Mungeli, Bilaspur Bansal CP, MD FIAP Pediatrician and Neonatologist Shabda Pratap Nursing Home Gwalior, MP Barua Ankur Assistant Professor Department of Community Medicine Sikkim Manipal Institute of Medical College Gangtok, Sikkim Batra Prerna Ascociate Professor Department Pediatrics Mahatma Gandhi Institute of Medical Sciences Sewagram, Wardha

Budhwani KS, MCh Professor and Head Department of Pediatric Surgery Gandhi Medical College Bhopal, MP Chatterjee Pallabh Consulting Pediatricians Kolkata Chawda Arun Pediatrician Fafdeh, Raipur, CG Faridi MMA Professor Pediatrics Department of Pediatrics UCMS and GTB Hospital Shahdara, Delhi Gupta Ashok Associate Professor Pediatrics SMS Medical College, Jaipur Gupta Vinay, MS Surgeon / Andrologist Bilaspur, CG Gurudatta HS, MD Mahasamund Hariramani Suresh, MD Children Hospital Tilda

Bhatt Ramesh Associate Professor Department of Pediatrics KMC, Manipal

Jain Karuna, MD Laparoscopic and Obstetric Surgeon Raminker Hospital, Purani Basti Raipur, CG

Bopardikar Ranjan Pediatrician Sparsh Children Hospital Bhilai, CG

Jain Navneet, MS Laparoscopy Surgeon Ramkinker Medical Institute Purani Basti, Raipur, CG

Jain Nirved, MCh Plastic and Cosmetic Surgeon Jeevan Memorial Hospital New Shanti Nagar, Raipur, CG Jain Vijay, MD, FIAP Consulting Pediatrician Gaya, Bihar Kalda Sunil, MCh Cosmetic Surgeon Kalda Nursing Home, GE Road Raipur, CG Khanduja MK, MD, DCH Pediatrician Nehru Nagar, Bhilai, CG Khandwal Onkar, MD Assistant Professor Pt JNM Medical College, Raipur Madharia Arun, MS Orthopedic Surgeon Gayatri Hospital, Raipur, CG Madharia Nalini, MD Laparoscopic and Obstetric Surgeon Aashirvad Hospital, Sunder Nagar Raipur, CG Mandric SK Pediatrician Science College Colony, Raipur CG Menghani Jagdish, MD Katora Talab, Raipur, CG Menghani Kavita, MD Telebandha, Raipur, CG Mukhopadhyay Sagori JK Lon Hospital, SMS Medical Hospital, Jaipur

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viii Nebhani Shyam, DCH Nebhani Nursing Home Ravigram, Raipur, CG Pal Ranbir Associate Professor Department of Community Medicine, Sikkim Manipal Institute of Medical College Gangtok, Sikkim Pardal Rakesh, MD Chief Medical Officer Mahasamund Patel GS, MD Professor Pediatrics Medical College, Indore, MP Patel Jyotish, MD Sickle Cell Anemia Foundation Bardoli, District–Surat, India Phulzhele NL Head, Department of Pediatrics Medical College, Raipur Pulak Parag, MS, MCH Pediatric Surgeon Consultant Pediatric Surgeon Raipur, CG Purohit Alok, MD Professor and Unit Head JK Lon Hospital, Sawai Man Singh (SMS) Hospital, Jaipur

Spotters in Pediatrics Rathi ML, MD, DCH Senior Pediatrician Budhapara, Raipur, CG

Sharma Shayam Resident Medical Officer Swapnil Nursing Home, Raipur

Saha Abhijeet Senior Lecturer in Pediatrics Government Medical College and Hospital, Chandigarh 160030

Shukla Lalit, MS Shree Netralaya, Ashirwad Towers Raipur, CG

Sahai KM, MD KMS Hospital Jaipur, Rajasthan Saify Rubina, MD Pediatrician and Neonatologist Indrawati Colony, Raipur, CG Sarbhai KP, MD Sarbhai Nursing Home Sunder Nagar, Raipur, CG Savant AP Senior Pediatrician District Hospital, Durg, CG Sethi Sidhartha Kumar Department of Pediatrics UCMS and GTB Hospital Shahdara, Delhi Shadangi Lokesh, MD District Hospital, Raigarh, CG Sharma Sanjay, DM Consultant Neurologist Modern Medical Institute Lalpur, Raipur, CG

Sur DK Senior Pediatrician Bayron Bazar, Raipur, CG Tamer SK, DM HOD Department of Neurology, JNM Institute, Bhilai, CG Thakur Vasudev, MD Bhatapara Uttamani Naresh, MD, DNB Pediatrician and Neonatologist Civil Lines, Raipur, CG Verma Amar MD, DCH, PhD, WHO Fellow

Associate Professor RIMS, Ranchi, Jharkhand Yadu Shirish, MS Consulting Surgeon Modern Medical Institute, Lalpur Raipur, CG

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Foreword Dear Dr Anoop Verma, I congratulate you for an excellent work and here is my comment. “I am aware of your zest to capture images of patients including videos that I have myself witnessed during your academic presentations at various conferences. I am sure one stores what one sees more than what one just reads and that is how we learn better from patients rather than mere textbooks. This compilation of large number of images would certainly help all of us to memorise those conditions that in turn would help us to spot them quickly. I appreciate your efforts to disseminate knowledge in unique way. I strongly recommend for each one of us to make best use of such a ready reckoner. Short relevant text accompanying the images is a bonus.” With regards and best of wishes

Prof. YK Amdekar (Retd) Pediatrics Dept., JJ Hospital, Mumbai Hon. Prof of Pediatrics, Jaslok Hospital, Mumbai

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Foreword Childhood illnesses constitute as major public health problem in many developing countries including India. There are innumerable emerging and re-emerging diseases, genetic and metabolic disorders and rare syndromes, which are extremely difficult to diagnose. A large number of these diseases especially infectious if diagnosed early can save the lives of these babies. Genetic disorders always remain an enigma and diagnostic dilemma to majority of clinicians. There are innumerable dermatological conditions in children, which baffles the clinician. Normal physiological conditions in the newborn are often regarded as pathological and cause panics in the minds of the parents and some physicians. It is, therefore, important to differentiate normal from abnormal conditions in the newborn. I earnestly appreciate the sincere effort being done by Dr Anoop Verma in putting together excellent photographs of high quality in the book “Spotters in Pediatrics” which would prove to be a useful readymade armamentarium in the hands of Pediatricians and Physicians. I have known Dr Verma as one of the most dynamic and hardworking pediatrician in the country. He has excellent organizational capacity and in a short period of time attained various important positions in Indian Academy of Pediatrics in both State and at National level. This book will be an extremely useful guidebook for all clinicians. The book contains very useful chapters of infectious diseases, neonatology, genetic and metabolic disorders, nephrology, rare syndromes and dermatological conditions in children. By bringing out this important book, Dr Verma has made significant contribution in the field of Pediatrics bridging the gap of a near famine of relevant topics in this field. I am sure, the book will find a place in the desktop of many clinicians in the country. I wish Dr Anoop Verma all success in his further effort in this direction.

AK Dutta Vice-Principal, Director Professor and HOD, Pediatrics Kalawati Saran Children’s Hospital Lady Hardinge Medical College New Delhi

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Foreword It is a matter of great privilege and pride for me to learn about the launching of the publication Spotters in Pediatrics by Dr Anoop Verma, ex-National Vice-President of IAP. The field of pediatrics has tremendously expanded in the last decade with expertise in various sub-specialties. In addition the recent advances in the field of perinatology, newborn care, molecular biology, drug therapy, genetics and emerging-reemerging infection have added new dimensions in the understanding the childhood problems for the practicing pediatrician. Thus, it has become necessary for the medical professional to update himself with the recent know-how in the field of newborn and childhood diseases from the diagnostic and management point of view. This book is an excellent collection of clinical photographs of common to rare pediatric diseases along with short text for ready reference. It will definitely prove to be a guiding source of knowledge for the busy practicing pediatrician and will serve as ready reckoner. I would like to congratulate Dr Anoop Verma for this innovative academic venture. With personal regards and best wishes

Uday Bodhankar Deputy Secretary General CAMHADD UK International Council Member ASPR Japan Chairman ICMCH and INSPCAN India Hon. Prof. of Pediatrics – IGMC Nagpur Past President IAP / ISTP / SCM – IPA Ramdaspeth, Nagpur 440012 MS, INDIA Ph: (R) 0091- 712- 2425020 / 2445554 (H) 0091 -712- 2459090 / 2422505 FAX : 0091- 712- 2428145 / 2421017 Email : [email protected]

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Foreword One of the essential requirements of scientific progress and research is correct documentation of facts. In western countries scientific data and observation were meticulously recorded and stored. Out of 2.1 billion children below first year of life, the 3/4th are in developing countries, have very high under-five mortality. Pediatrician in India has contributed a lot in reducing infant mortality and in various childhood illnesses. Contributions of Indians in world literature are still below expectation. “Spotters in Pediatrics” by Dr Anoop Verma will fill this gap to great extent. Dr Anoop Verma is very hard working and sincere pediatrician with a habit of recording observations, which has given rise to this monograph for which he deserves great compliments. Spotters in Pediatrics should find its place in bookshelf of practicing pediatricians, graduates in pediatrics and general practitioners. It should stimulate them for good record and for bringing more books like this in future.

Padmashree AT Dabke MD PhD Dean, Professor and Head (Rtd) Department of Pediatrics Pt JNM Medical College, Raipur

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Preface Pediatrics is a fascinating branch, not because we deal with innocent patients but because we draw conclusions from what parents say and what we assess in examination of patient. It is more or less a role of detective. To become a good detective it is not only to read the text thoroughly but also to memorise and search the abnormalities. “A picture is worth a thousand words, and a video is worth a thousand pictures. I cannot define an elephant unless I have seen one.” A glimpse of clinical condition is sufficient to repercuss your brain later, when you come across similar condition in future. The art of making diagnosis by gestalt is not inherited; it needs repeated practice mixed with interest in it. The more you see a condition, the more you go through the text, less is the chance, the condition is escaped your recognition. Experience is not one day job, it is gradual building of memory of variety of cases you come across over the years. It is an old saying you are never late in medical practice. The journey to this fascinating subject can begin at any point of time, provided you have constant zeal and persistent interest in this subject. In clinical practice we must wear the spectacle of astute clinical observer and behave like assiduous and prolific recorder of observation. The syndromic child is most of the time considered a gift of God and hence, further treatment by parents comes to an end. It is on the part of treating physician to counsel such parents and make them aware of the condition and accordingly encourage future course of disease and its inheritance. There are certain conditions which have strong possibility and probability to recur in future generation, on the contrary, there are conditions which almost occurs once (sporadic mutation).The concept of counseling should spread to all parents of such children. Rarely do we find parents who are concerned of their child’s disease and its course. The usefulness of a clinical atlas in medicine is known since ages. The present shape of “Spotters in Pediatrics” is the result of years of devotion and hard work. With its classified and authoritative format this atlas supplies the answer to question that may arise during examination or consultation, giving advice on symptoms, diagnosis and therapeutic measures. We hope that the detailed but concise information given in this atlas will prove of value to students and experienced practitioners alike.

Anoop Verma

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Acknowledgements One’s body may be handsome, wife beautiful, fame excellent and varied, and wealth like unto Mount Meru; but if one’s mind be not attached to the lotus feet of Guru, what thence, what thence, what thence ? Adi Shankara Guruvastakam, Verse 1 In my development as a pediatrician, apart from my destiny, there was huge share of my devoted teachers, who have virtually paved my way to clinical pediatrics. My deep regards and respect to my teachers Late Prof DS Dave, Prof NG Prasan, Padmashree Prof AT Dabke and Prof Ashok Rawat. I have got great encouragement and blessings from stalwarts in pediatrics Prof YK Amdekar, Prof AK Dutta, Prof Uday Bodhankar, Prof HP Singh. From my core of heart I convey my sincere gratitude to them. I convey my thanks to our inspirational National President of IAP 2007 Dr Naveen Thacker, who virtually introduced me to publisher, and given me the initial push. I am indebted to our past National Presidents Dr Raju Shah and Dr Nitin Shah for keeping me on track by their able guidance. My hearty thanks to my chapter editors Sanjay Sharma, Pulak Parag, Navneet Jain, Arun Agrawal, Ashok Gupta and Ramesh Bhatt. Their infectious interest has virtually lessened my workload. To come up with plethora of clinical photographs is not easy task, but due to important contributions from contributors. I convey my deep sense of regards to the contributors of this book. A sense of deep regards to my colleagues at Chhattisgarh and my friends, namely DK Sur, ML Rathi, KP Sarbhai, Vijay Makhija, Ashwani Agrawal, SK Mandrik, KW Deoras, Pradeep Sihare, Rakesh Sahu, Madhu Shree Deshpande, Ashok Mehta and Lokesh Shadangi their powerful support, encouragement and guidance has always lifted my morale. I am indebt to all of them. My due regards to M/s Jaypee Brothers Medical Publishers (P) Ltd., especially Shree Tarun Duneja, General Manager, (Publishing), for his interest and support. Last but not the least, my wonderful colleague and friend Shyam Sharma, who has kept me free to complete this life time work. Lastly, I am overwhelmed to convey my gratitude to my whole family Sudhir, Nalini, Manoj, Aarti, Soumiya, Anuj and Siddhi for creating encouraging milieu favorable to this work.

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Contents CHAPTER 1 INFECTIOUS DISEASES ------------------------------------------------------ (1–14) Measles ---------------------------------------------------------------------------------------------------- 1 Mumps ----------------------------------------------------------------------------------------------------- 3 Chickenpox ----------------------------------------------------------------------------------------------- 4 Molluscum contagiosum -------------------------------------------------------------------------------- 7 Warts (Verrucae) ----------------------------------------------------------------------------------------- 7 Tubercular lymphadenopathy --------------------------------------------------------------------------- 8 Scrofuloderma -------------------------------------------------------------------------------------------- 9 Lupus vulgaris -------------------------------------------------------------------------------------------- 9 Tetanus ----------------------------------------------------------------------------------------------------- 9 Tetanus neonatorum ----------------------------------------------------------------------------------- 10 Kawasaki disease ----------------------------------------------------------------------------------------11 Hydatid disease ------------------------------------------------------------------------------------------11 Ascaris lumbricoides ---------------------------------------------------------------------------------- 12 Herpes zoster ------------------------------------------------------------------------------------------- 13 CHAPTER 2 DERMATOLOGY --------------------------------------------------------------- (15–44) Atopic dermatitis --------------------------------------------------------------------------------------- 15 Alopecia ------------------------------------------------------------------------------------------------- 16 Stevens-Johnson syndrome --------------------------------------------------------------------------- 18 Toxic epidermal necrolysis --------------------------------------------------------------------------- 20 Henoch-Schönlein purpura --------------------------------------------------------------------------- 20 Seborrheic dermatitis ---------------------------------------------------------------------------------- 22 Hemangioma and vascular malformation ----------------------------------------------------------- 23 Cutis marmorata telangiectatica congenita --------------------------------------------------------- 25 Nevus of Ota -------------------------------------------------------------------------------------------- 25 Epidermolysis bullosa --------------------------------------------------------------------------------- 26 Acrodermatitis enteropathica ------------------------------------------------------------------------- 27 Scabies --------------------------------------------------------------------------------------------------- 28 Head lice ------------------------------------------------------------------------------------------------ 30 Psoriasis ------------------------------------------------------------------------------------------------- 31 Collodion baby ----------------------------------------------------------------------------------------- 32 Harlequin fetus ----------------------------------------------------------------------------------------- 33 Ichthyosis vulgaris ------------------------------------------------------------------------------------- 34 Cutis laxa ------------------------------------------------------------------------------------------------ 35 Scleroderma --------------------------------------------------------------------------------------------- 36 Tinea corporis ------------------------------------------------------------------------------------------- 37 Urticaria ------------------------------------------------------------------------------------------------ `38 Dermatographism -------------------------------------------------------------------------------------- 39 Dermatofibroma ---------------------------------------------------------------------------------------- 40

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Spotters in Pediatrics Congenital melanocytic nevus -----------------------------------------------------------------------Juvenile xanthogranuloma ---------------------------------------------------------------------------Ectodermal dysplasia ---------------------------------------------------------------------------------Hypomelanosis of Ito ----------------------------------------------------------------------------------

40 42 42 43

CHAPTER 3 NEONATOLOGY ----------------------------------------------------------- (45–70) Erythema toxicum -------------------------------------------------------------------------------------- 45 Mongolian spot ----------------------------------------------------------------------------------------- 46 Salmon patch ------------------------------------------------------------------------------------------- 46 Milia ----------------------------------------------------------------------------------------------------- 47 Junctional nevus ---------------------------------------------------------------------------------------- 47 Cutis marmorata ---------------------------------------------------------------------------------------- 48 Cephalohematoma ------------------------------------------------------------------------------------- 48 Mastitis neonatorum ----------------------------------------------------------------------------------- 50 Supernumerary nipples -------------------------------------------------------------------------------- 51 Neonatal teeth ------------------------------------------------------------------------------------------ 51 Neonatal hymenal tags -------------------------------------------------------------------------------- 51 Neonatal vaginal bleed -------------------------------------------------------------------------------- 51 Sternocleidomastoid tumor --------------------------------------------------------------------------- 52 Milia crystalline ---------------------------------------------------------------------------------------- 52 Miliaria rubra ------------------------------------------------------------------------------------------- 53 Acne neonatorum -------------------------------------------------------------------------------------- 53 Bullous impetigo --------------------------------------------------------------------------------------- 54 Baby of diabetic mother ------------------------------------------------------------------------------- 54 Beckwith-Wiedeman syndrome ---------------------------------------------------------------------- 56 Asymmetric crying facies ----------------------------------------------------------------------------- 57 Amniotic band ------------------------------------------------------------------------------------------ 58 Congenital syphilis ------------------------------------------------------------------------------------- 60 Oral thrush ---------------------------------------------------------------------------------------------- 60 Single umbilical artery -------------------------------------------------------------------------------- 60 Birth trauma --------------------------------------------------------------------------------------------- 62 Erb-Duchenne palsy ----------------------------------------------------------------------------------- 63 Hemorrhagic disease of newborn -------------------------------------------------------------------- 64 Twin to twin transfusion------------------------------------------------------------------------------- 65 Nonimmune hydrops ---------------------------------------------------------------------------------- 66 Epignathus ---------------------------------------------------------------------------------------------- 67 Sacrococcygeal teratoma ------------------------------------------------------------------------------ 68 Ophthalmia neonatorum ------------------------------------------------------------------------------- 68 Ear abnormality ---------------------------------------------------------------------------------------- 69 CHAPTER 4 ENDOCRINOLOGY ------------------------------------------------------------ (71–80) Gynecomastia ------------------------------------------------------------------------------------------- 71 Idiopathic precocious puberty ------------------------------------------------------------------------ 72 Cushing’s syndrome ----------------------------------------------------------------------------------- 73 Congenital hypothyroidism --------------------------------------------------------------------------- 74 Micropenis ---------------------------------------------------------------------------------------------- 77 Ambiguous genitalis ----------------------------------------------------------------------------------- 78

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CHAPTER 5 PEDIATRIC SURGERY ------------------------------------------------------ (81–136) Abscess -------------------------------------------------------------------------------------------------- 81 Thyroglossal duct cyst --------------------------------------------------------------------------------- 82 Dermoid cyst -------------------------------------------------------------------------------------------- 83 Cystic hygroma ----------------------------------------------------------------------------------------- 84 Preauricular sinus -------------------------------------------------------------------------------------- 85 Cleft lip and cleft palate ------------------------------------------------------------------------------- 87 Inguinal hernia ------------------------------------------------------------------------------------------ 88 Umbilical hernia ---------------------------------------------------------------------------------------- 89 Lumbar hernia ------------------------------------------------------------------------------------------ 90 Omphalocele -------------------------------------------------------------------------------------------- 91 Gastroschisis -------------------------------------------------------------------------------------------- 92 Achalasia cardia ---------------------------------------------------------------------------------------- 94 Infantile hypertrophic pyloric stenosis -------------------------------------------------------------- 95 Duodenal atresia and stenosis ------------------------------------------------------------------------ 97 Disorders of rotation and fixation of intestine ------------------------------------------------------ 99 Pneumoperitoneum in newborn --------------------------------------------------------------------- 102 Intussusception ---------------------------------------------------------------------------------------- 104 Hirschsprung’s disease ------------------------------------------------------------------------------- 105 Anorectal malformations ----------------------------------------------------------------------------- 108 Rectal prolapse ---------------------------------------------------------------------------------------- 110 Congenital diaphragmatic hernia -------------------------------------------------------------------- 111 Eventration of diaphragm ---------------------------------------------------------------------------- 114 Phimosis ------------------------------------------------------------------------------------------------ 115 Paraphimosis ------------------------------------------------------------------------------------------- 116 Labial adhesion ---------------------------------------------------------------------------------------- 116 Hair-tourniquet syndrome ---------------------------------------------------------------------------- 117 Vesicoureteral reflux ---------------------------------------------------------------------------------- 119 Posterior urethral valve ------------------------------------------------------------------------------- 121 Bladder exstrophy—epispadias --------------------------------------------------------------------- 123 Rhabdomyosarcoma ---------------------------------------------------------------------------------- 125 Conjoint twins ----------------------------------------------------------------------------------------- 128 Empyema thoracis ------------------------------------------------------------------------------------- 132 CHAPTER 6 BONE DISORDERS ---------------------------------------------------------- (137–149) Rickets -------------------------------------------------------------------------------------------------- 137 Scurvy -------------------------------------------------------------------------------------------------- 139 Osteogenesis imperfecta ------------------------------------------------------------------------------ 141 Congenital club foot ---------------------------------------------------------------------------------- 143 Digital abnormalities ---------------------------------------------------------------------------------- 144 Polydactyly --------------------------------------------------------------------------------------------- 144 Syndactyly --------------------------------------------------------------------------------------------- 145 Brachydactyly ----------------------------------------------------------------------------------------- 145 Ectrodactyly (Lobster-Claw defect) ---------------------------------------------------------------- 146 Multiple cartilaginous exostosis --------------------------------------------------------------------- 147 Greenstick fracture ------------------------------------------------------------------------------------ 147 Congenital scoliosis ----------------------------------------------------------------------------------- 148

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CHAPTER 7 NEUROLOGY ----------------------------------------------------------------- (150–178) Neurofibromatosis ------------------------------------------------------------------------------------ 151 Tuberous sclerosis ------------------------------------------------------------------------------------- 153 Sturge-Weber syndrome ------------------------------------------------------------------------------ 155 Ataxia telangiectasia ---------------------------------------------------------------------------------- 156 Parry-Romberg syndrome ---------------------------------------------------------------------------- 157 Cutis verticis gyrata ----------------------------------------------------------------------------------- 157 Klippel-Trenaunay-Weber syndrome --------------------------------------------------------------- 158 Waardenburg syndrome ------------------------------------------------------------------------------ 159 Neurocysticercosis ------------------------------------------------------------------------------------ 159 Bells palsy ---------------------------------------------------------------------------------------------- 161 Marcus Gunn phenomenon -------------------------------------------------------------------------- 162 Myasthenia gravis ------------------------------------------------------------------------------------- 163 Rett’s syndrome --------------------------------------------------------------------------------------- 164 Angelman syndrome ---------------------------------------------------------------------------------- 166 Duchenne muscular dystrophy ---------------------------------------------------------------------- 167 Neural tube defect ------------------------------------------------------------------------------------- 168 Spina bifida -------------------------------------------------------------------------------------------- 168 Sincipital meningoencephalocele ------------------------------------------------------------------- 170 Anencephaly ------------------------------------------------------------------------------------------- 171 Iniencephaly ------------------------------------------------------------------------------------------- 172 Microcephaly ------------------------------------------------------------------------------------------ 172 Agenesis of corpus callosum ------------------------------------------------------------------------ 173 Lissencephaly ------------------------------------------------------------------------------------------ 174 Joubert syndrome ------------------------------------------------------------------------------------- 175 Large head (macrocephaly) -------------------------------------------------------------------------- 176 Phenytoin-induced gingival overgrowth ----------------------------------------------------------- 177 Drug induced dystonia ------------------------------------------------------------------------------- 177 CHAPTER 8 GENETIC ----------------------------------------------------------------------- (179–219) Down syndrome --------------------------------------------------------------------------------------- 179 Edward’s syndrome ----------------------------------------------------------------------------------- 181 Patau’s syndrome -------------------------------------------------------------------------------------- 182 Saldino-Noonan syndrome --------------------------------------------------------------------------- 183 Majewski dysplasia ----------------------------------------------------------------------------------- 184 Thanatophoric dysplasia ----------------------------------------------------------------------------- 185 Achondrogenesis -------------------------------------------------------------------------------------- 186 Asphyxiating thoracic dysplasia -------------------------------------------------------------------- 188 Achondroplasia ---------------------------------------------------------------------------------------- 189 Turner’s syndrome ------------------------------------------------------------------------------------ 191 Noonan’s syndrome ----------------------------------------------------------------------------------- 193 Marphan’s syndrome --------------------------------------------------------------------------------- 194 Robin anomalad --------------------------------------------------------------------------------------- 195 Albinism ------------------------------------------------------------------------------------------------ 196 Hurler’s syndrome ------------------------------------------------------------------------------------ 197 Morquio’s syndrome ---------------------------------------------------------------------------------- 198

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Progeria ------------------------------------------------------------------------------------------------- 199 Goldenhar syndrome ---------------------------------------------------------------------------------- 200 Meckel-Gruber syndrome ---------------------------------------------------------------------------- 201 Charge syndrome -------------------------------------------------------------------------------------- 202 Apert’s syndrome ------------------------------------------------------------------------------------- 203 Disorganization-like syndrome ---------------------------------------------------------------------- 204 Kabuki make-up syndrome -------------------------------------------------------------------------- 205 Lesch-Nyhan syndrome ------------------------------------------------------------------------------ 205 Poland sequence --------------------------------------------------------------------------------------- 206 Osteopetrosis ------------------------------------------------------------------------------------------- 207 Potter syndrome --------------------------------------------------------------------------------------- 207 Fibular hemimelia ------------------------------------------------------------------------------------- 208 Proboscis lateralis ------------------------------------------------------------------------------------- 208 Bardet-Biedl syndrome ------------------------------------------------------------------------------- 209 Vater syndrome ---------------------------------------------------------------------------------------- 210 Blepharophimosis syndrome ------------------------------------------------------------------------ 211 Milroy-Hereditary lymphedema --------------------------------------------------------------------- 211 Macrodystrophia lipomatosa ------------------------------------------------------------------------ 212 MRKH syndrome ------------------------------------------------------------------------------------- 212 Genetic counseling ------------------------------------------------------------------------------------ 215 CHAPTER 9 MISCELLANEOUS CONDITIONS -------------------------------------- (220–240) Tetralogy of Fallot ------------------------------------------------------------------------------------ 220 Congenital ptosis -------------------------------------------------------------------------------------- 223 Congenital cataract ------------------------------------------------------------------------------------ 223 Periorbital cellulitis ----------------------------------------------------------------------------------- 223 Rhinosporidiosis--------------------------------------------------------------------------------------- 224 Vitamin A deficiency --------------------------------------------------------------------------------- 225 Geographic tongue ------------------------------------------------------------------------------------ 226 Fissured tongue ---------------------------------------------------------------------------------------- 226 Foreign body nose ------------------------------------------------------------------------------------ 227 Ingested foreign body -------------------------------------------------------------------------------- 227 Foreign body aspiration ------------------------------------------------------------------------------ 228 Palatal perforation ------------------------------------------------------------------------------------- 229 Extravasation injury ---------------------------------------------------------------------------------- 230 Intraosseous transfusion ------------------------------------------------------------------------------ 233 Sickle cell disease ------------------------------------------------------------------------------------- 234 Index ---------------------------------------------------------------------------------------------------- 241

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Chapter

1

Infectious Diseases

MEASLES (Figs 1.1 to 1.3) DEFINITION  Measles (derived from Latin misellus meaning ‘miserable’) is a highly contagious viral disease sometime called as rubeola (Latin rubeolus = reddish) or morbilli (Latin morbus = disease). It is caused by an RNA virus called as paramyxovirus.  Human is the only known natural host for the measles virus. There is no natural animal reservoir of the virus, although monkeys can be infected following human contact.1 CLINICAL FEATURE  Its incubation period ranges from 10 to 12 days. It is most infectious during the early prodromal phase of the disease when large quantities of virus are present in nasopharynx secretion and rashes have yet to develop.  It is characterized by (3C), Cough, Coryza and Conjunctivitis. The exanthem of the disease is erythemetous papule (Morbilliform) is a significant feature of eruption. It starts along hairline and proceeds downward. Peak eruption occurs at third day coincides with peak of the fever and constitutional symptom. Rashes resolves by 5th and 8th day, later branny desquamation as brown staining of skin follows.  Enathem: Koplicks spot seen 2 days before and 2 days after the rash seen opposite lower molar. It is white popular dots on an erythematous buccal mucosa looks like ‘Salt grain’ sprinkled on a red background. A transverse line of conjunctival inflammation sharply demarcates along the eyelid margin called as Stibsons line.

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Fig. 1.1: A 6-year-old patient Fig. 1.2: Morbilliform rashes presented with cough, coryza, fever, photo-phobia and classical rash

Fig. 1.3: Conjunctivitis with peculiar rash

COMPLICATIONS  Complications of Measles is mainly respiratory, e.g. Otitis media, Pneumonias (Interstitial pneumonia and secondary bacterial pneumonia), Laryngotracheal bronchitis. NeurologicalFebrile seizures, SSPE, Encephalitis. Miscarriages, premature births and congenital malformations have been occasionally associated with measles.2 Other complications are diarrhea, hepatitis, appendicitis, corneal ulceration, and myocarditis.  Subacute Sclerosing Pan Encephalitis (SSPE) is chronic measles encephalitis, having 8 years average age of onset. As a rule past infection of measles at early stage is always there before the age of two years. It presents as personality change and declining school performance. Fundus examination at early stage shows pigmentary changes in the macula. Myoclonic seizures usually develops next, classical EEG changes are evident in the form of periodic burst of spike and wave complexes (approximately 5 to 7 seconds). Later there is rapid neurological deterioration to spasticity, dementia and involuntary movement develops and later dementia supervenes. Anti measles antibody in csf is usually positive. Intraventricular alpha interferon gives some improvement in few cases. Prognosis is usually poor. TREATMENT  Is always supportive. Bed rest, antipyretics and adequate fluid intake are indicated. Isolate from non-immune children until five days after the rash has appeared.  Pulmonary complications are usually due to secondary bacterial infections and has to be treated by antibiotics.  Currently UNICEF and WHO3,4 has recommended vitamin A supplementation to all cases of measles in developing country. Children 6 months-old to 1 year-old: 100,000 IU by mouth as a single dose, repeated the next day and again at 4 weeks. Children 1 year-old or older: 200,000 IU as a single dose, repeated the next day and again at 4 weeks.

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Infectious Diseases

3

PREVENTION5  Measles vaccine is given at age of 9 months, subcutaneously on the upper arm or anterolateral thigh. It can be given even at 6 months in measles outbreaks. This vaccine is a live attenuated virus vaccine, it results in actual infection and multiplication in the body, which mimics actual infection of measles but is usually asymptomatic. Point of precaution while reconstitution of multidose measles vaccine is to maintain strict asepsis has, since there is no antibacterial contents in the vial, some cases of staphylococcal sepsis/toxic shock syndrome is seen.  MMR vaccine is recommended to all children by IAPCOI. For infants given measles vaccine at 9 to 12 months MMR vaccine is given between 15 and 18 months. If measles vaccine was missed altogether then one dose of MMR vaccine is given at or after 12 months.

MUMPS (Figs 1.4 and 1.5) DEFINITION  Mumps (from an old English word meaning ‘Grimace’) or endemic parotitis is an acute infectious disease marked by a painful enlargement of one or both parotid salivary gland. RNA virus of genus paramyxovirus causes it. CLINICAL FEATURE  Clinical feature is characterized by pain and swelling in one or both parotid glands. The gland fill the gap between posterior border of mandible and mastoid and then extends downward and forward. The swelling pushes earlobe upward and outwards and the angle of mandible is no longer visible. The swelling subsides within 3 to 7 days.  The swelling is painful and tender especially elicited by tasting sore liquid such as lemon juice. There is redness and swelling in the opening of stensons duct. In severe cases swelling and edema may approach manubrium and upper chest because of lymphatic obstruction.  It is estimated that 20 to 40 percent of infection results in no symptoms, 40 to 50 percent is nonspecific symptoms and in only 30 to 40 percent in typical acute parotitis.6  Diagnosis is usually clinical. Elevated serum amylase, IgM and IgG Ab against mumps virus are detectable and lastly viral culture. COMPLICATION  Meningo encephalitis is most common, occurs in 5 to 15 percent6 cases. Ten percent of these cases seen over 20 yrs, mortality from this condition accounts to 2 percent.  Orchitis and epididymitis—less commonly seen in preadolescent boys, it accounts to 15-35 percent in adolescent boys. Orchitis follows parotitis after 8 days. It can occur without parotitis. Abrupt onset, fever with chills and rigors, nausea and vomiting, lower abdominal pain. Right testis is often involved. Infertility is rarely seen with bilateral involvement.  Pancreatitis: There is abdominal pain, persistent vomiting and fever. The pain is epigastric and steady, often resulting in the child assuming antalgic position with hips and knees

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Fig. 1.4: Enlarge parotid gland

Fig. 1.5: Two brothers suffering from mumps (Beware of spread of infection to unprotected ones)

flexed, sitting upright, or lying on the side. The serum amylase is typically elevated for up 4 days. Ultrasonography and CT scan have major role in diagnosis. Other complication includes—oophoritis, myocarditis, arthritis, thyroiditis, deafness.  Recurrent parotitis: It is common to notice recurrent idiopathic enlargement of parotid gland. It is unilateral but can involve other side also. It produces mild pain and usually lasts 2 to 3 weeks. Commonly notice in spring. It starts at age of 6 years and persists for many years. Congenital or autoimmune defects of the duct are presumed to be the cause of recurrence. Each episode last for few days to 2 weeks before spontaneous resolution occurs. TREATMENT  Treatment is always symptomatic: Antipyretics/ acetaminophen/ibuprofen. Bed rest, diet. Local warm or cold pack in the region of swelling. Good oral hygiene.  Isolation of patient till swelling persists. The period of infectivity is 7 days before and 9 days after the onset of parotitis.  Sialogogue agents (vitamin C, lemon chewing gums). It is said it drain the saliva and prevents stagnation and later secondary infection. Sore items induces pain in parotid if it is discomforting to patient it can better avoided.  Antibiotic if ascending infection from mouth is suspected.  Orchitis should be treated by local support and bed rest. Mumps arthritis is treated with NSAID/Corticosteroid.  Pancreatitis: Pain relief, fluid and electrolyte balance to be maintained. Nil orally till serum amylase returns to normal and clinical symptoms has resolved. PREVENTION7 Mumps vaccine is given as component of MMR vaccine given between 15 and 18 months.

CHICKENPOX (Figs 1.6 and 1.7) DEFINITION  Varicella is highly contagious exanthemetous illness caused by varicella zooster virus, a member of herpes virus group.

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Fig. 1.6: Neonate with chickenpox

Fig. 1.7: Chickenpox rashes

 Primary infection occurs by circulating virus in the nasopharynx through droplet inoculation. Local replication occurs here leading to viremia and dissemination by circulating mononuclear cells.  It is highly contagious 1 to 2 days before and shortly after onset of rash, but lesion are infectious until they have turned into dried crusts. CLINICAL FEATURES  Its incubation period is 14 to 16 days. The disease is characterized by mild fever and constitutional symptoms in children.  The rashes appear as crops and acquire a characteristic centripetal distribution (more lesion are found on torso than on face and extremities). It rapidly progresses from red macule to vesicle, pustule and crusts within 3 to 4 days. The rash produces intense itching. Lesion is also seen in scalp and mucous membrane. The classical lesion is a vesicle surrounded by erythematous base described as ‘a dew drop on rose petal’.  Varicella is most severe above 13 years.  The vesicles get secondarily infected by beta hemolyticus Streptococcus (GBHS) may result into streptococcal toxic shock syndrome, necrotising fasciitis Figs 1.8A and B, or purpura fulminance.  Apart from other complication acute cerebellar ataxia is common, but is transient and may improve of own.  Immunity following chickenpox is life long and hence, it doesn’t recur, but the virus may persists in the dorsal root ganglia after an acute infection and may get reactivated to cause shingles or herpes zooster. Its involvement is always unilateral dermatomal distribution and stops in the midline.

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A

B Figs 1.8A and B: (A) Necrotizing fasciitis (B) Spread of secondary bacterial infection leading to extensive necrotizing fasciitis

TREATMENT  In healthy children varicella is a benign, self-limiting disease with low rate of complication. It usually requires symptomatic treatment.  Analgesics/antipyretics/local soothing agents and antibiotics if secondary infection is suspected. Aspirin should not be used to avoid Reye’s syndrome.  Acyclovir is recommended for normal individual 13 years and above and for immunocompromised host. Acyclovir in dose of 20 mg/kg/dose 4 times a day for 5 days within 24 hours of onset of skin lesion will reduce the severity of the disease.  In uncomplicated varicella, acyclovir is not recommended but on choice can be used to modify the course of disease. Acyclovir doesn’t hampers development of immunity against varicella.  In complicated varicella like encephalitis and viral pneumonia, intravenous acyclovir (10 mg/ kg/dose 8 hrly) must be used. The treatment must be continued for 7 days or till no fresh lesions appears for 48 hours which ever is later. PREVENTION8 Active Immunization  Varicella vaccine (live attenuated).  IAPCOI opines that varicella vaccine is not recommended for universal immunization in India at present. One has to emphasize the benign nature of and rarity of complications with varicella in young children.  It may be offered to children of high socioeconomic status at 12 months to 12 years single dose and for person over 12 years of age, two doses, 4 to 8 weeks apart.  Other indications are children with chronic heart and lung diseases, HIV infection ( but with CD4 counts above 25% of age related norms), in leukemia (but in remission for at least 1 year), household contacts of immunocompromised children.

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 Varicella zooster immunoglobulin (VZIG).  Given to susceptible at risk of developing severe varicella and in Immunocompromised children.8 To neonates whose mother experienced onset of varicella 5 days, or less before delivery or within 48 hours after delivery.

MOLLUSCUM CONTAGIOSUM (Fig. 1.9)  This is a skin infection caused by a poxvirus (DNA). It is a common infection in children. It is transmitted by skin contact with an infected person.  The infection presents as small discrete, round, pearly-white growths, with central umblication on the skin. There may be single or multiple growths on the skin. These growths are usually symptomless.  Common sites of infection are the eyelids, neck, trunk and Fig. 1.9: Molluscum contagiosum anogenital area.  Treatment- a) Trichloroacetic acid applications or b) Cryotherapy with liquid nitrogen applications or c) Light electrosurgery, d) Tretinoin gel for small lesion, e) Manual curettage of big lesions.

WARTS (VERRUCAE) (Figs 1.10A and B)  Warts are intraepidermal tumor of skin caused by human papilloma virus (HPV). TYPES  Common wart (Verruca vulgaris): They are discrete flesh colored, single or multiple papules with a rough surface more common in hands but may occur anywhere.  Flat wart (Verruca plana): They are grouped as flat topped, flesh colored or pigmented papules with smooth surface, common on the face.  Anogenital wart (Condylomata accuminata): It is cauliflower like or pink filiform sessile papule with rough surface. It can be acquired from birth canal or acquired from sexual abuse.  Plantar wart.  Periungual wart. TREATMENT  Conservative: No treatment spontaneous regression occurs within 2 years in most cases.  20 percent Podophylline is applied with a toothpick twice daily for 3 days. Podophylline is a plant extract, is a microtubule inhibitor that blocks the cell division. In excess doses it is neurotoxic and produces areflexic coma.

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B

Figs 1.10A and B: (A) Condylomata in 7 months old child (B) Venereal wart in an adolescent boy

 Use of salicylic acid and lactic acid locally.  Tretinoin gel locally at night.  Oral cimetidine 30 mg/kg/day in three divided doses for 3 months.

TUBERCULAR LYMPHADENOPATHY (Figs 1.11A to C)  Cervical and mediastinal glands are affected most commonly, followed by axillary and inguinal: in 5 percent more than one regional group is involved.  Significant constitutional disturbance and evidence of associated tuberculosis is lacking.  The lymph nodes are painless, initially mobile, and occasionally discharge through the skin causing a “Collar-stud” abscess.  Diagnosis • Ziehl-Neelsen microscopy (positive in only 25% cases). • Histology revealing caseating granuloma. • Culture on Lowenstein-Jensen or Bactec media.

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Figs 1.11A to C: Tubercular lymphadenopathy. (A) Large solitary cervical lymph node proved to be tubercular on histopathological examination. (B) X-ray chest of the same patient depicting hilar adenopathy. (C) Scrufuloderma over cervical region

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 Treatment and Prevention • Short course chemotherapy (as for Pulmonary TB). • Paradoxical enlargement as a result of hypersensitivity reaction occurs occasionally during or even after completion of therapy. • Surgical excision is sometime necessary. • Prevention as for pulmonary tuberculosis.  Scrufuloderma (Fig. 1.11C) results from enlargement, cold abscess formation, and breakdown of a lymph node, with extention to the overlying skin. Linear or serpiginous with dissecting fistulas and subcutaneous tracts studded with soft nodule may develop. Spontaneous healing may take years and eventually a cord like keloid scar results.

LUPUS VULGARIS (Figs 1.12A and B) It is a rare chronic progressive form of tuberculosis of the skin that develop in an individual with moderate to high degree of tubercular sensitivity induced by previous infection. It is due to direct skin involvement from underlying joint and nodes. A solitary lesion consists of brownish red, soft papule that has an apple-jelly color when examined by diascopy. Chronicity is characteristic, and persistence and progression to plaque over many years are common. Treatment consists of excision of small lesions and antitubercular drugs.

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Figs 1.12A and B: Lupus vulgaris: (A) Lupus vulgaris in a nine-year-old boy. (B) Lupus vulgaris in different parts of the body. Courtesy-Dr Ranbir Pal, Dr Ankur Barua, Dr Pradeep Barua, Sikkim Manipal Institute of Medical Sciences

TETANUS (Figs 1.13A and B)  It is caused by C.tetani, which is a gram positive, spore forming anaerobic bacilli.  Although the incidence of tetanus is reducing due to wide coverage by vaccination, still tetanus neonatorum cases are seen in India due to practice applying mud and cowdung over cord.  From the contaminated wound the toxin tetanoplasmin travels proximally along the nerve to nervous system. It produces tetanus by two mechanisms; by blocking acetylcholine release

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A

B Fig. 1.13A and B: (A) Tetanus in grown-up child, note the facial expression during the spasm (B) Spasm in neonate

at myoneural junction and by countering the inhibitory influence on muscle reflex arc. It results in increased activity of lower motor neuron, which produces muscle rigidity and spasm. Once fixed the toxin cannot be neutralized by antitoxin. CLINICAL FEATURES  After an incubation period of 5 to 10 days painful stiff jaw muscle (trismus) appears followed by difficulty in opening the mouth (Lock jaw). Stiffness spreads to neck, back, chest and abdomen. This is rigid stage of the disease.  Intermittent painful contraction of the muscle then starts, the spasmodic stage. The spasm causes grimacing of face (risus sardonicus), and arching of neck and back (opisthotonus). Spasm of respiratory and laryngeal muscle causes respiratory failure. TREATMENT  Ideally should be treated in intensive care.  Human Tetanus Immunoglobulin (TIG) 3000 to 6000 IU IM followed by debridement of the wound. The role of ATS, i.e. antitetanus serum is now less important. It is only given when TIG is not available. It is given 50,000 to 100,000 units half IM and half IV.  Benzyl penicillin IV or IM for 10 days to eradicate the existing foci of infection and stop further toxin production.  Sedation by diazepam, but should be nursed in quit environment. Tracheostomy is indicated in severe cases, to guard against the life threatening laryngeal spasm.  Prevention: Tetanus is prevented by immunizing children by DPT under the age of five and by TT thereafter following the IAP immunizing schedule. TETANUS NEONATORUM (Fig. 1.13B)  Tetanus neonatorum is potentially serious and fatal disease. It usually begins between 3 and 10 days. There is progressive difficulty in sucking, swallowing and excess crying is there. The spasms and stiffness develops sometime opisthotonus posture is seen.  Prevention: It is prevented by immunizing pregnant mothers by two dose of tetanus toxoid between 16 and 36 week of pregnancy and only one dose of TT in the subsequent pregnancy.

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KAWASAKI DISEASE (Figs 1.14A to C)  The etiology of this condition is unknown. Search for an infective agent has so far proved unsuccessful. It is claimed to be an abnormal immunological response to variety of microbial agent including streptococci, rickettsiae, viruses and house dust mite. The greatest prevalence is in Japan. It occurs predominantly in children below five years of age.  Clinical Features and Diagnosis • Five main features are recognized: fever for more than 5 days, non-purulent bilateral conjunctivitis, reddened lips and oral mucosa, raw red tongue, erythema of limbs including palms and soles, and edema may be present (later periungual or more generalized desquamation occurs), cervical adenopathy. • Persistent leucocytosis, high erythrocytic sedimentation rate (ESR) or plasma viscosity and thrombocytosis (2nd week onwards) are characteristic laboratory features. • Up to 20 percent of cases develops coronary aneurysm due to coronary arteritis during later phase of illness.  Diagnosis and Treatment • Diagnosis is by clinical and laboratory features. • Other diseases have to be ruled out like scarlet fever, TSS, erythema multiforme, juvenile stills. • IV Gamma globulin and aspirin during the early stage reduces the risk of coronary aneurysm formation. • Prolong follow-up should be advised.  Prognosis: usually benign, about one percent of cases ends fatally, mostly from cardiac complication.

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Figs 1.14A to C: Kawasaki disease, note the exfoliation of palms and soles. Photographs by Dr KM Sahai, Jaipur

HYDATID DISEASE (Figs 1.15A and B)  The dog is the definitive host of the small tapeworm Taenia echinococcus that produces large number of eggs in the faeces, contaminating grass and infecting sheep, which are the usual intermediate hosts. The cycle is completed by the ingestion of infected raw sheep offal by dogs. Human becomes accidental intermediate host by close contact with dogs.

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B Figs 1.15A and B: Hydatid disease. (A) Contrast CT scan showing multiple hydatid cyst. (B) CT chest showing hydatid cyst in lungs

 In humans, the ingested ova develop to form embryo worms, which penetrate the gut wall and invade the tissues. Most of the embryos are destroyed, but one or more may survive and become encysted, usually in the liver.  Usually there is single cyst, but in 30 percent cases there are multiple cysts, usually in single organ. Cysts have been described in every organ but favored sites are liver, lungs, spleen, brain, eyes, heart, bone and genitourinary system.  Hydatid cysts reach a diameter of 1 cm in 5 months and continue to grow as large as 35 cm containing liters and ‘Hydatid sand’.  Clinical features: infection become manifest either because of expansion of cyst or by rupture and release of the cyst contents. Clinically the cyst present as a palpable, slowly growing liver tumor or as partially calcified lesion on chest X-ray. Large cysts in the liver may rupture spontaneously, causing sudden pain, fever allergic rash and eosinophilia. Cysts may calcify gradually with the death of all living worm tissue.  Diagnosis: Usually by radiography, ultrasongraphy and CT scan. Serological tests such as indirect hemogglutination or ELISA can be of value but false negatives occur, particularly in pulmonary disease and in children. The Casoni skin test is less reliable than serological test.  Treatment: Albendazole in three cycles of 28 days each may succeed in killing infective cysts. Hepatic Hydatid cysts are very slow growing and may not require any treatment unless large and causing compression. Operative removal of cyst under pre- and post albendazole treatment regimen is the mainstay of therapy. Calcified cysts should be left alone. Non-surgical aspiration of the cyst is dangerous and should be avoided.

ASCARIS LUMBRICOIDES (Figs 1.16A to C)  Ascaris lumbricoides is an intestinal round worm, and adult worm ranges from 20 to 35 cm long and is as thick as a pencil, although the male tends to be small. They are particularly more prevalent in condition of poor sanitation, with an individual patient harboring up to 1000 worms and mature female producing up to 20,000 eggs daily. The eggs need to

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Figs 1.16A to C: Ascaris lumbricoides infestation. (A) Child harboring hundreds of roundworm (B) Adult worm in stool. (C) Abdominal USG revealed multiple horizontal streaks depicting worm body





 

mature for 2 to 3 weeks in the soil. The spread is fecal-oral with an incubation period of 4 to 8 weeks. The ingested embryonated eggs hatch in the duodenum and the larvae penetrates through the wall into the blood or lymphatics. They are carried to the liver, heart and thence to pulmonary circulation, here they penetrate through the capillaries into the alveoli. They then ascend the bronchial tree, enter the esophagus and pass down to the small intestine. Here they mature, mate and produces eggs 45 to 60 days after ingestion. The only symptoms in majority are the excretion of worms or eggs in the stool. In the small percentages of cases gastrointestinal or pulmonary symptoms may arise, probably related to the number of eggs. Loffler’s syndrome occurs when the larva migrates through the lungs. Cough, wheezing and breathlessness are the most important common presenting features. Heavy worm load in children may cause abdominal pain and features of intestinal obstruction and failure to thrive. Diagnosis is usually by passage of adult worm in stool, detection of ova in stool. Barium meal examination, occasionally adult worm can be picked up in abdominal ultrasonogram. Treatment consists of use of antihelminth drugs like albendazole, mebendazole, etc. No drug is effective in pulmonary phase of infection.

HERPES ZOSTER (Figs 1.17A and B)  Zoster results from reactivation of latent VZV in a dorsal root or extramedullary cranial nerve ganglion. The virus travels down the sensory nerve to the area of skin supplied by the nerve and produces the typical skin lesion. Zoster in the very young children is probably related to decreased CMI at the time of primary VZV infection.  Clinical features • Prodromal pain: it persists for 2 to 3 days. • Rashes initially red patches with vesicles progressing to pustule which scab and then separate. New lesions continue to occur for 3 to 5 days. Scabbing and separation are usually complete by 2 to 4 weeks. Single dermatome is usually involved, but lesion can be seen extending to adjoining dermatome due to overlapping innervations.

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Figs 1.17A and B: Herpes zoster. (A) Note the red patche with vesicle over anterior and lateral chest. (B) Note the same strip of vesicle on backside, the dermatomal distribution

• •

Dorsolumbar dermatomes are most frequently involved followed by trigeminal, cervical and sacral. Acute phase pain—common during rash evolution.

 Complication depend on site of vesicles - ranging from skin infection, ocular, neuralgia, meningoencephalitis, Ramsay Hunt syndrome, cutaneous and visceral dissemination.  Treatment • Antiviral drugs (acyclovir, famiclovir,valaciclovir) shortens the duration of acute illness. • Analgesics • In PHN amitrytylene topical cool spray and transcutaneous nerve stimulation are often helpful. REFERENCES 1. 2. 3. 4. 5. 6. 7. 8.

Meyer HM et al. Am J.Dis. Child 1062; 103: 307. Jes Persen CS et al. Acta Pediatri Scand 1977; 66: 376. Measles: The urban Challenge, UNICEF NY. 1991. WHO/UNICEF: Wkly Epidemiol Rew 1987; 62: 133. IAP guide book on immunization 2004; 16-18. CDC Data. Mumps surveillance Jan 1977, Dec 1982. US Dept of Health and Human Service 1984. IAP guide book on immunization, 2004; 38. IAP guide book on immunization, 2004; 25-26.

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Dermatology

ATOPIC DERMATITIS (Figs 2.1A and B) DEFINITION Atopic dermatitis or eczema is an itchy, dry, hypersensitive skin disorder affecting many people. It is common in children but can occur at any age. It is not infectious or contagious.  The exact cause of atopic eczema is unknown. It may be hereditary. The patient or some family members may have other hypersensitive conditions like asthma or hay fever. Infections like Staphylococcus aureus, herpes simplex virus help in flaring of the dermatitis.  The rash may appear red, wet and weepy or dry, thickened and scaly. Scratching often aggravates the rash. The skin thickens and becomes darker. It is a chronic condition. It can affect any part of the body, particularly the elbow bends, back of the knees and the neck. Infantile Type (seen from 2 months to 2 years). Classically cheeks and shin are involved. It produces intense itching, lesion is dry, erythematous, excoriated plaques may then become lichenified and hyperpigmented. Spontaneous remission is common by 2 years. Childhood Type—Seen above 5 years, seen at flexural area, neck, wrists antecubital and popliteal areas. PATHOGENESIS There are two hypotheses: 1. Increased in cyclic AMP phosphodiesterase activity, and 2. Decrease in cell mediated immunity both of these are responsible in over activity of the T-helper cell (TH2) subset of T-lymphocyte and thus, leads to significant inflammation.

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Figs 2.1A and B: (A) Atopic dermatitis. The lesions in childhood form are flexural in distribution as contrast to infantile form where there is axillary involvement. (B) antecubital areas involvement

MANAGEMENT 1. Care of dry skin by taking brief bathing with mild soap, and patting (not rubbing) the dry skin leaving moisture. Application of moisturizer or emollients after bath like hydrophilic petroleum, etc. 2. Steroids: Mild steroids like hydrocortisone is applied over face and in infants. Moderate potent steroid like (clobetasone butyrate 0.050%) for subacute lesion. The potent steroids like betamethasone dipropionate 0.050 percent, flucinolone acetornide and mometasone for chronic lesions. 3. Antibiotics are used for infected cases. Beta lactam antibiotics are best-suited drugs here for at least 2 to 3 weeks. 4. Antihistamines: Hydroxyzine 1mg/kg/day at bed time double the usual dose. Other drugs used are diphenhydramine, doxepin, loratidine, cetrizine.

ALOPECIA (Figs 2.2A and B) DEFINITION Hair loss, alopecia, is the result of changes in the hair follicle. If the changes are transient (as in alopecia areata) and non destructive of the hair matrix, there is eventual regrowth. Condition that causes destruction of the hair matrix (such as folliculitis decalvans or physical trauma) lead to the formation of scars or atrophy resulting in permanent alopecia. CLASSIFICATION It is classified into two groups: Non-scarring alopecia usually divided into localised or diffuse, and cicatricial or scarring alopecia. THE HAIR CYCLE To understand the pathogenesis of alopecia requires knowledge of the hair follicle cycle and its role in disorders of the hair and scalp.

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Figs 2.2A and B: Alopecia. (A) Alopecia areata in a 2-year-old boy. (B) Tinea capitis. Circumscribed area of hair loss without scalp change and hair broken off at the follicular orifice

Hair growth occurs in cycle. Anagen phase (Growing phase): In this phase hair grows about 2 mm a week for 2 to 5 years or longer. This is followed by short, involutional phase, the catagen phase. In this phase mitosis ceases at the hair bulb and the matrix is enveloped by shortening outer root sheath. Telogen phase: It is characterized by non-pigmented “club” hair. The new anagen hair pushes out the old telogen hair, beginning the new cycle. The human scalp has approximately 100,000 hair follicles of which some 5 to 10 percent are in the telogen phase. Since the telogen phase lasts for 3 months for each individual hair, the number of normally lost telogen hairs is 50 to 100 daily. In acutely stressful events, such as birth, auto accidents, illness with high fever, and acute psychiatric illness may results in a rapid conversion of growing hairs to resting hairs. Following the events by 2 to 4 months, the hairs are shed over 3 to 4 months. TELOGEN EFFLUVIUM (Fig. 2.3)  Telogen is the name given to the acquired diffuse alopecia that results from rapid conversion of scalp hairs from growing state to resting state.  Diagnosis: It is made by plucking atleast 50 hairs from the child’s scalp and examining the roots to determine whether they are growing or resting. In anagen phase, the hair will have a pigmented core and a bulbous root that is larger in diameter than the hair shaft. In telogen phase, the external root sheath is absent, or fragmented pigment is often absent, and the root of the hair is narrower than the caliber of the outer hair and frequently curved.  Treatment: Patient should be reassured that normal hair growth would return within 6 months. ANAGEN EFFLUVIUM It is an acute, severe diffuse inhibition of growth of anagen follicles; the loss is greater than 8090%. It is caused by radiation and cancer chemotherapeutic drugs and hypervitaminosis A.

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 Fig. 2.3: Telogen effluvium. Note acquired diffuse nonscarring alopecia

ALOPECIA AREATA (Fig. 2.2A)  It is characterized by complete or almost complete hair loss in circumscribed areas without scalp changes.  A positive family history is seen in 10 to 20 percent of patients.  Nail disease is seen in 46 percent cases ranging from pitting 1 to 2 mm in nail plate.  Prognosis for most children is excellent. Complete hair growth occurs within a year in 95 percent cases. Spontaneous remission is the rule.  Treatment • Anthralin used locally for its irritant effect (stimulate hair growth). • Intralesional injection of triamcinolone solution. • Topical corticosteroid.

STEVENS-JOHNSON SYNDROME (Figs 2.4 and 2.5) DEFINITION  It is a severe type of adverse reaction mostly due to drugs, some times due to infectious agent and is characterized by a distinct eruption and involvement of atleast two mucous membranes and the erosions involve more than 20 percent area. It is also called as erythema multiforme major. When mucous membrane are not involved it is called as erythema multiforme minor. The severe form of erythema multiforme spectrum is toxic epidermal necrolysis (TEN) here more than 30 percent of area is affected by erosion.  Etiology: Drugs like—Anticonvulsants- Barbiturate, diphenhydantoin, carbamazepine, Lamotrigene. Antibiotics—Penicillins, sulphonamides. Nonsteroidal anti-inflammatory drugsIbuprofen and naprosyn. Infectious agent like Mycoplasma pneumoniae, herpes simplex, etc. CLINICAL FEATURES  The skin lesions are seen of many types erythematous macule, purpuric macule, papules, blisters leading to erosions. Target or iris lesion are quite specific, individual erosions are < 3 cm in diameter.

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Figs 2.4A to D: Stevens–Johnson syndrome—In three-year-old child, rashes appeared after starting cotrimoxazole for diarrhea, note the progress of the lesion. The beginning of the eruptions (extreme left), subsequent evolution of the rashes in the middle and the recovery (extreme right).

 It may precede upper respiratory symptoms and may cause exudative and erosive stomatitis, conjunctivitis, or vulvovaginitis, arthritis, arthralgia, pneumonia, and hepatitis. TREATMENT  Multidisciplinary approach like involvement of pediatrician dermatologist and ophthalmic surgeon.  Offending drug to be discontinued.  Management of fluid and electrolyte imbalance.  Skin care in the form of warm tap water compresses and application of petroleum ointment over denuded area.  Use of corticosteroid is controversial. If used at all it has to be used early and if there is no response within 4 days it has to be discontinued. Prednisolone has to be used in dose of 2 mg/kg/d. PROGNOSIS Produces significant morbidity and has a protracted course. Its mortality ranges from 5 to 15 percent.

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Figs 2.5A to D: SJS-Erythematous, dark macules along with mucosal lesions in a two-year-old child who was kept on carbamazepine for seizure. See the evolution of the rash from extreme left to extreme right, the recovery.

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TOXIC EPIDERMAL NECROLYSIS (TEN) (Fig. 2.6)  TEN is severe form of drug reaction involving skin and mucous membrane; it is severe form of erythema multiforme spectrum with blistering involving more than 30 percent of body surface.  Etiology: Drugs like—Anticonvulsants- Barbiturate, diphenhydantoin, carbamazepine, Lamotrigene. Antibiotics—Penicillin, sulphonamides. Nonsteroidal anti-inflammatory drugsibuprofen. CLINICAL FEATURES  Clinically skin becomes necrotic dark colored and peels off in sheets measuring > 3 cm. The bullae and erosion involve > 30 percent of body area. Face and upper part of the body is prominently involved. Nikolski sign is positive that is rubbing the adjacent normal skin of blister enlarges the erosion but it is not specific for TEN. Apart from skin involvement there is involvement of mucous membrane in the form of exudative stomatitis, purulent conjunctivitis, and vulvovaginitis.  It has very explosive onset, within 24 hours disease takes its full-blown shape.  Mortality is as high as 30 percent.

Fig. 2.6: Dark skin peels off in sheets measurung > 3 cm, bullae and erosion involves more than 30 percent area

TREATMENT  Treatment should be taken in the burn unit with simultaneous involvement of ophthalmologist, dermatologist and pediatrician.  Search and stop the precipitating factors. Adequate fluid and electrolyte balance has to be maintained.  Antibiotics to control the infections.  Skin care has to be as in burn cases, wash the skin by normal saline, remove the loose skin and blisters, apply petroleum jelly to provide barrier.

HENOCH-SCHÖNLEIN PURPURA (Figs 2.7A to C) DEFINITION  HSP is hypersensitivity disorder, also called as anaphylactoid purpura. It is vasculitis of small vessels. It is the nonthrombocytopenic purpura seen in children.

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A

B

C

Figs 2.7A to C: Henoch-Schönlein purpura. (A) A 10-year-old boy presented with severe sore throat. Examination of throat revealed white patch over the tonsils, throat swab culture identifies the streptococcal beta hemolyticus. The white patches have to be differentiated from white patch of Infectious mononucleosis, where other features of IMN are also present. This patient was kept on adequate penicillin coverage. A review, after a week, the patch disappeared but parents noticed purpuric rashed over lower limb, hand and buttocks which was palpable over lower limbs. (B and C) The platelet count was normal patient was clinically diagnosed as a case of HSP

ETIOLOGY Etiology is unknown but typically it is precipitated by upper respiratory infection. It may be precipitated by bacterial infection (group A beta hemolytic Streptococcus), viral infection (human parvovirus B19), drugs like captopril, ciprofloxacin, aminosalicylic acid, insect bite and some unknown allergen. PATHOGENESIS  Pathogenesis is uncertain. Probably high frequency of HLA-DRB1*07. Increase in serum concentration of cytokines tumor necrosis factor alpha (TNF alpha) and inter leukin 6 seen in active disease. There is increase in antistreptolysin O (ASO) titre to suggest involvement of group B Streptococcus. There is deposition of IgA and C3 in small vessel of skin and glomerulus inducing vasculitis seen by immunofluorescence technique. This induces inflammation. CLINICAL FEATURE  The onset may be acute or insidious may take weeks to month. TYPICAL SKIN RASH  Begins as pinkish maculopapule that initially blanches. It progress to palpable purpura.  Lesion develops as crops within 3 to 10 days.  Distribution: From buttock down the lower extremity some time upper extremity is involved. These rashes evolve from red to purple to rusty brown due to hemosiderin deposition.  Ten percent patient shows recurrences even as late as several years.

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 GIT-symptoms- (75%) cases. Colicky abdominal pain, vomiting, gross or occult blood in stool. Intussusception is suggestested by empty right lower abdominal quadrant and red currant jelly stool.  Joint symptoms- (>75%) localised at knee joint and ankle.  Renal involvement- (25% to 50%) Hematuria and proteinuria.  CNS involvement- rare but seizure, paresis and coma occurs. COMPLICATIONS  The major complications are nephritic syndrome, hypertensive encephalopathy, chroni glomerulonephritis (5% cases) and bowel perforation and intussusception some times testicular torsion is also reported. TREATMENT  There is no definite treatment and is mainly supportive. Most of the complaints are selflimiting.  Bed rest, bland diet.  Acetaminophen is used to control fever, pain and edema.  Prednisolone in dose of 1 to 2 mg/kg BW is used in severe gastrointestinal renal and CNS symptoms and it produces dramatic improvement.  Aspirin in case of thrombotic episodes.  Cochicine in alternate days dose in case of rheumatic nodule. PROGNOSIS  HSP is a self-limiting disease with overall excellent prognosis. Less than one percent cases develop chronic renal disease, therefore, serial urine analysis is required and follow-up renal surveillance if initial symptoms were pertaining to renal disease.

SEBORRHEIC DERMATITIS (Fig. 2.8)  It is type of chronic dermatitis associated with excess of sebum production.  It is seen over scalp, face mid chest or perineum and is seen in extreme of pediatric age group, i.e. neonate and the adolescent. The other areas involved are eyebrows, central oval of the face, ears, neck, post auricular fold and intertriginous area.  The scalp appears greasy with accumulation of scales trapped in the sebum.  In adolescent it appears as greasy scale. Erythema in the nasolabial folds and scalp may be seen. TREATMENT  Low potency topical steroids applied twice a day for several days.  Keratolytic shampoo applied over scalp for several minutes, while scalp is scrubbed with a soft brush or toothbrush to remove scale and crust. Low potency steroids is then applied after shampoo. This procedure is then applied daily till resolution occurs.  Oral Biotin therapy is considered in biotin responsive dermatitis.

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 Fig. 2.8: Seborrheic dermatitisGreasy scales involving scalp, face and eyebrows.

HEMANGIOMA AND VASCULAR MALFORMATION (Figs 2.9 to 2.11)  Vascular birthmarks are one of the common forms of birth defect.  According to Mulliken and Glowacki1 classification, which divides vascular birthmarks into hemangiomas and vascular malformations.2 Initially at early stage they may look alike but in later life they have distinct natural history.  Mulliken and Glowacki Classification of vascular malformation.

HEMANGIOMA-VASCULAR MALFORMATION Superficial

Capillary (Port wine)

Mixed

Telangiectatic

Deep

Hypertrophiccapillary (angiokeratoma) Venous (cavernous) Arteriovenous Lymphatic Cutis marmorata telangiectatica congenital

CLINICAL FEATURE Types  Superficial (Strawberry hemangioma) are most common type which appears between 2nd and 4th week of life. They are asymptomatic, blanches and compressible in nature. They are bright red and popular.  Deep (Cavernous) hemangioma—present at birth, bluish and nodular.  Mixed superficial and deep.

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Fig. 2.9: Hemangioma of lower lip

Fig. 2.10: Portwine stain over Fig. 2.11: Hemangioma right right half of face cheek in an infant with cavernous component

 Only 20 percent hemangioma are present at birth, rest 80 percent arise between 2 and 8 week age. At the time of presentation it is difficult to predict what form and size of hemangioma will eventually takes place.  Natural course of hemangioma- at age 4 to 8 weeks there is rapid growth phase, which continues until the infant is 6 to 9 months of age. This rapid growth phase is characteristic of hemangioma even more than growth of infant. At this stage it is soft and compressible. The phase is followed by phase of regression that begins at second year, and by 5 years age regression is 50 percent and by 9 years almost 90 percent hemangioma regresses. Natural course of vascular malformation- usually present at the time of birth and expresses slow growth.  Complication- in the form of ulceration and infection. It compromises the function of the part which depends upon the site of its presence. Some times hemangioma rapidly enhances in size and is associated with life threatening hemorrhages and features of shock and is called as Kasabach-Merritt syndrome. This is due to trapping of circulating platelets and coagulation factor. TREATMENT  All hemangiomas which have potential to interfere with vital function should be treated, however, other indications are as follows:  Kasabach-Merritt syndrome  High output cardiac failure  Obstruction of vital function  Ulceration  Infection TREATMENT OPTIONS  Oral glucocorticoids- 30 to 60 percent patient responds to oral prednisolone 2 mg/kg/d morning doses for 4 weeks and later tapering it to alternate days. Responsive hemangioma

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will demonstrate effect of treatment within 7 to 10 days as softening of tumor, lightening of color or a noticeable decrease in growth rate.  Intralesional injection of triamcinolone acetonide solution (40 mg/ml) 1 to 3 mg/kg/ every 2 weeks time.  Interferon alpha 2 a- 1 million U/m2/day subcutaneous injection till regression is complete (Fever and 10% incidence of spastic diplegia is reported by its use).  Vascular specific pulse dye laser has been shown to induce regression in 75 percent cases of hemangioma with ulceration. Non-specific laser therapy such as a carbon dioxide or the neodymium: YUG (Yttrium aluminium, garnet) may cause scarring and hamper outcome.

CUTIS MARMORATA TELANGIECTATICA CONGENITA (Fig. 2.12) In cutis marmorata telangiectatica congenital a mottled pattern of blue or dusky-red erythema is seen from birth. The lesion is usually bilaterally seen on the extremities and the trunk, but oftensingle extremity is involved. There is gradual increase in size of the lesion, expected over one year and then gradually fade out at adulthood. Musculoskeletal and other vascular malformations are sometime associated.

Fig. 2.12: Cutis marmorata telangiectatica congenita

NEVUS OF OTA (Fig. 2.13) SYNONYM  Nevus Fascoceruleus Ophthalmomaxillaris, Nevus Fascoceruleus Acromiodeltoidalis. DEFINITION  It is pigmentary disorder affecting specific anatomic location. It is due to melanocytic arrest in the dermis, which is an abnormal location for melanocyte.  It is an area of extensive blue patches like area of dermal melanocytic pigmentation of the sclera and the skin adjacent the eye. Pigmentation apart from sclera also involves conjunctiva, iris, and optic nerve, cheeks forehead, scalp, alae nasi and ears.

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 Fig. 2.13: Nevus of ota

 Lesion presents in 60 percent cases at birth. Rest appear at puberty. In few cases it is acquired.3 They are mostly unilateral.  The skin lesion is permanent in nature and can be removed by Q- switched ruby laser for cosmetic reason. NEVUS OF ITO  The area of involvement is acromioclavicular region and upper chest.

EPIDERMOLYSIS BULLOSA (Figs 2.14A and B)         

It is hereditary disorder characterized by bullae formation as a result of trauma. EB is divided into scarring and nonscarring type. Nonscarring type Epidermolysis bullosa simplex (EBS) Junctional epidermolysis bullosa (JEB) Scarring type (Dystrophic) includes subepidermolysis bullosa Epidermal bullosa simplex EBS of hands and feet (Weber-Cockayne Disease) Generalized EBS (Koebner variant). Epidermolysis bullosa simplex- is an autosomal dominant condition. The most common form is localized to hands and feet. Blisters have its first appearance in childhood and adolescence when the child experiences minor trauma. Warm weather worsens the disease. The condition improves with age.  Generalized EBS- is also an autosomal dominant condition. Onset may be at the time of birth or between 6 months and 12 months age. They are more numerous on distal extremities. Disease worsens in warm weather.  Distrophic epidermolysis bullosa- may be autosomal recessive and dominant type. They may have appearance of blisters at birth and associated with scar formation, growth retardation, dental and nail changes.

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A

B

Figs 2.14A and B: (A) Epidermolysis bullosa simplex lesions over soles of 4 year old child (B) Junctional epidermolysis bullosa in new born.There are multiple moist erosions involving fingers and perioral skin, and pressure points. Few bullae are large in size. Nails could also be affected. Hands and feet are relatively spared. Treatment for the condition is supportive. Photograph courtesy by Dr Ramesh Bhatt, KMC, Manipal.

 Molecular genetic studies in EB cases identified mutations in keratinocyte gene1, encoding there major structural protein: Keratins 5 and 14 in EBS, Laminin S in JEB and type VII collagen in dystrophic form.  Diagnosis: It is usually made by clinical, histopathological and molecular biology technique.  Blister Biopsy- is taken in severe cases by inducing blisters with pencil eraser or a suction device. A shave biopsy taken from normal skin into induced blister is preferred. This specimen has to be examined under light and electron microscope and immunofluorescent mapping.  Management is symptomatic and supportive.  Gentle handling, loose fitting clothes, gentle sponge bath.  Blisters can be opened by sterile scissor and roof allowed to collapse by gently compressing out the fluid.  Antisepsis for eroded area by topical antibiotic (Mupirocin). Antibiotics should be periodically changed to avoid bacterial resistance.  Low dose of systemic corticosteroid in severe cases.  Genetic counseling.

ACRODERMATITIS ENTEROPATHICA (Figs 2.15 and 2.16) DEFINITION  AE is an autosomal recessive disorder of zinc transport. It begins 1 to 2 month after birth lesions around acral region, recurrent diarrhea and failure to thrive. CLINICAL FEATURE  The erosions appear red moist areas over distal extremities including hands and feet, perioral and perineal area. Hairs may show peculiar red tint. Eye involvement in the form of photophobia, conjunctivitis and corneal dystrophy. Other features are chronic diarrhea, stomatitis, glossitis, paronychia, nail dystrophy, growth retardation and delayed wound healing.

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Fig. 2.15: Acrodermatitis enteropathica- Crusting perioral lesion

Fig. 2.16: Lesion over arm, legs and buttocks

DIAGNOSIS  Diagnosis is usually clinical supported by serum zinc level and serum alkaline phosphatase enzyme. Later is zinc-containing enzyme, in zinc deficiency the level of this enzyme is low. Precautions during collection of blood for serum zinc estimation is that blood should be collected in acid washed plastic tubes and syringes. This is due to avoid zinc contamination from glass tubes and other blood collecting devices. PATHOGENESIS  It is thought that zinc deficiency results in impairment of metalloenzyme activity which produces the clinical picture. TREATMENT  Oral zinc sulphate 5 mg/kg/day given in twice daily produces rapid clinical improvement. Apathy disappears within 24 hours and skin lesions and diarrhea resolves within 7 to 14 days.

SCABIES (Figs 2.17A to F) DEFINITION  Scabies is an infestation of skin caused by Sarcoptes scabiei hominis also called as itch mite. CLINICAL FEATURE  This itch mite burrows into the epidermis and irritates the skin causing scratching, which leads to excoriation, which further serves as portal or entry for pathogenic organism. It presents as intense pruritic papules over abdomen, dorsa of hand, flexurals surface of the wrist, elbow, periaxillary skin, genitalia and interdigital webs of the hand.  In infants its presentation differs. It presents as eczematous eruption of face and trunk as an acute dermatitis that is characterized by excoriation, erythematous papule, honey colored crusts and pustules.  In older children and adolescent head and neck are almost never involved.

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A

B

C

D

E

F

Figs 2.17A to F: Scabies (A) An infant with involvement of hands palm, soles and face (B) Involvement of dorsa of hand and interdigital areas (C) Eczematous eruptions in an infant (D) Involvement of male genitalia (E) Involvement of natal folds and buttocks (F) Involvement of dorsum of hands and finger webs in older age group

 Secondary infection is quite common in children due to Staphylococcus aureus or Streptococcus pyogens. Later is responsible for development of acute glomerulonephritis.  Crusted nodules present over trunk as S-shaped burrow are diagnostic. It is an ideal lesion for scrapping.  In mentally retarded children who are unable to scratch may have thousands of scabies mite and the lesion takes the form of diffuse hyperkeratosis and lichenification. It is seen on hands, feet and genitalia. This form of scabies is known as Norwegian scabies. TREATMENT  Maintenance of hygiene and local application of scabicidal drugs is the main stay of treatment.  Permethrine 5 percent application neck downward for 8 to 14 hrs produces 98 percent cure.4 Permethrin acts on the nerve cell membrane of the mite to disrupt the sodium channel current that regulates the polarization and subsequent paralysis and death of mite.  Method of application: Permethrin 5 percent cream is applied on cleansed and dry skin. In adults and children over 2 years, the cream should be applied to the whole body from neck down, rubbing lightly into the skin until the cream disappears. It is important to include all skin surface, such as between the fingers and toes, under the nails and on the sole of the feet. For babies under 2 years, apply to the face, neck, ears and scalp as well avoiding eyes.

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       

Spotters in Pediatrics It should be washed after 8 to 14 hrs after application to minimise the risk of allergic contact dermatitis. Gama benzene hydrochloride (Lindane) 1 percent applied once is curative 82 percent cases.5 Lindane when absorb systemically it can also result into CNS side effect. Ivermectin- is a systemic drug that has been approved for the treatment of onchocerciasis also use as scabicidal. Single dose of ivermectin 200 microgm/kg have a cure rate of 70 percent which increases to 95 percent with 2 doses at 2 week interval. For infant less than six months age sulphur 6 to 10 percent ointment twice day for three days can be used as alternative. In small children covering the arm and fingers after application of drug is recommended to avoid ingestion by licking. Control of itching: In scabies itching is due to immunological reaction by mite protein and it presents for 3 to 4 weeks after the treatment. It requires antihistamine (e.g. Pheniramine maleate) or local application of calamine lotion. Luke warm water bath with tetmosal soap may be beneficial. Cloths should be sun dried and to be changed daily. Mite die within 48 hrs when not on the human body. Therefore, infection by cloths is minimum. Treatment of secondary bacterial infection is by oral erythromycin. Treat all possible contacts.

HEAD LICE (PEDICULOSIS CAPITIS) (Fig. 2.18)  They usually presents with pruritus of the scalp, ears and neck, which can be occasionally very severe.  Nits (eggs) are oval and yellow-white, measuring 0.3 to 0.8 mm in size. They are found close to the scalp, firmly cemented to the hairs around ear and the occiput. Secondary impetigo, folliculitis, furunculous is common and may mask the primary disease. Treatment  Permethrin shampoo, single application for 10 minutes and then towel drying of the scalp. Can be repeated after a week.  Treat all contact at the same time. Fine tooth hair comb is advised to remove the nits.  Instruct the family to wash the clothing and bedding in very hot water for 10 minutes.  Apply petrolatum bid for 8 days and remove the nits manually in cases of eyelashes nits (crab louse).

 Fig. 2.18: Head lice (Pediculosis capitis)

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PSORIASIS (Figs 2.19 A and B) SYNONYMS Lepra alphos, psoriasis vulgaris. INCIDENCE Psoriasis is a common skin disease of childhood. In over third of psoriatic patients, disease begins in childhood or adolescence. In many countries incidence varies from 1 to 3 percent of population. PATHOGENESIS It is not clear, but a rapid epidermal cell turnover is claimed to be the cause. Normally it takes 28 days for epidermal cell to travel from basal layer to surface of the skin but in psoriasis it takes only 3 to 4 days to reach the surface. SIGNS  The eruption is characterized by erythematous macule or papules covered by dry, silvery scales, which when scrapped off, reveal a pinpoint bleeding (Auspitz sign).  Small lesion tends to coalesce forming plaques of varied shapes. The distribution is usually symmetrical. Nail involvement is common. As a rule psoriatic patched in children is milder in as compared to adults. CLINICAL VARIANTS  Napkin psoriasis—occurs in folds of the diaper area of infants.  Guttate psoriasis—this is an eruption of small (less than 1 cm), round or oval lesion, mainly on the trunk, which appears with sudden onset, and follows upper respiratory infection.

A

B

Figs 2.19A and B: Psoriasis (A) Scalp involvement results in accumulation of thick scales throughout the scalp (B) Guttate psoriasis in an old child. Drop like white silvery plaques seen over extremities and trunk

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 Follicular psoriasis—there is tiny horny pointed lesion around hair follicles, usually on the extensor aspect of the extremities.  Psoriasis of scalp—scaliness is more evident due to scanty hairs. And scalp is the first site affected. SYMPTOMS The condition is usually asymptomatic, but there may be mild pruritis. Psychological problem may develop in sensitive children. COURSE Chronic, with period of remissions and exacerbation, later may be aggravated by emotional stress. TREATMENT  Parents of the child should be informed as to the nature and chronicity of the disease. Since lesions are tiny and soft, topical medium to high potency corticosteroids are usually effective.  Resistant cases may need coal tar and salicylic acid preparation at low concentration (1% to 3%).  Antibiotics if streptococcal infection is suspected.

COLLODION BABY (Figs 2.20A to C)  It is a one of the primary group of inherited disorder of cornification characterized by pattern of scaling, inherited pattern, distinct clinical feature and histopathological change.  New born with an encasement of shiny, tight inelastic scale, resembling oiled parchment is designated as having collodion membrane, which subsequently sheds off.  The condition is usually a manifestation of Congenital Ichthyosiform Erythroderma or lamellar icthyosis. Infrequently, an affected infant has normal skin after the membrane is shed.  There is presence of ectropion, flattening of ears and nose and fixation of lip in an O-shaped configuration. The hair may be absent or may perforate the horny covering.  The collodion membrane is composed of greatly thickened stratum corneum that has been saturated with water. As the water content evaporate in extra uterine life, large fissure.  It is important to differentiate the collodion baby from harlequin ichthyosis as the latter rarely survives past the first few days of life.  The presence of collodion membrane doesn’t allow predicting that the baby will necessarily develop ichthyosis and spontaneous healing may occur. Skin biopsy of collodion membrane is usually not diagnostic. Most collodion babies do have a form of ichthyosis and majority of them develops feature of lamellar ichthyosis, bullous ichthyosis, X-linked ichthyosis, Netherton’s syndrome and gauchers disease have also been reported to present as collodion babies.

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A

B

C

Figs 2.20A to C: Collodion babies in a family. Autosomal recessive inheritance. (A) First child at birth. (B) Second child at birth. (C) Both child, elder is 4 years old with extensive lamellar ichthyosis. Second one in nenatal period

 The complication in the form of cutaneous infection, aspiration pneumonia, hypothermia or hypernatremic dehydration from excess transcutaneous fluid loss as a result of increase skin permeability may occur.  The outcome is uncertain and accurate prognosis impossible with subsequent development of ichthyosis. TREATMENT  Treatment initially consists of high fluid intake to avoid dehydration and transepidermal fluid loss and use of heated humidified incubator, emulsifying ointment and retinoids.

HARLEQUIN FETUS (Figs 2.21 A to C)  Harlequin fetus is rare disorder of keratinization or a severe form of lamellar ichthyosis and represents autosomal recessive disease.  At birth skin is markedly thickened with ridges, cracks and horney plates seen almost all over body. There is severe ectropion and chemosis of the eye, flattened nose and ears, lips everted with gaping. Nails and hair may be absent. Joint deformity with restricted mobility is seen. They are prone to respiratory distress and infections. Prognosis is poor and most patient die within first week an occasional one survives longer.  The common histopathological features include hyperkeratosis, accumulation of lipid droplets within corneocyte and absence of normal lamellar granules. TREATMENT  Strict hygiene, high fluid intake preventing dehydration by use of humidified incubators and application of emulsifying ointments. Oral retinoids such as etretinate may be useful.  Prenatal diagnosis- by fetoscopy, fetal skin biopsy and amniocentesis for cells between 17th and 21st weeks of gestation.

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A

B

C

Figs 2.21A to C: Harlequin fetus: (A) Disfigured baby, tight constricting integument, digital loss. (B) Severe ectropion and O-shaped mouth. (C) Horny cracks of the skin

ICHTHYOSIS VULGARIS (Figs 2.22A to D)  Ichthyosis is a hereditary skin disorder characterized by dryness and excessive scaling. There are five types of Ichthyosis and each is differentiated from other by mode of inheritance, age of onset and characteristic distribution of scale.  Ichthyosis vulgaris is an autosomal dominant condition characterized by diffuse fine scales over the extensor aspect, sparing of flexures and hyperlinear palms. It is often associated with atopic dermatitis. TREATMENT  Use of emollient (Urea cream, ammonium lactate cream).

A

C

B

D Figs 2.22A to D: Ichthyosis vulgaris

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Dermatology  Keratolytic cream.  Oral retenoids.  Genetic counseling. SYNDROMES ASSOCIATED WITH ICHTHYOSIS       

Netherton syndrome. Sjögren’s larson syndrome. Rud syndrome. Congenital hemidysplasia ichthyosis limb defect (CHILD) syndrome. Keratitis ichthyosis, deafness (KID) syndrome. Refsum’s syndrome. Trichothiadystrophy.

CUTIS LAXA (Fig. 2.23)  Cutis laxa is a autosomal recessive or autosomal dominant disorder. This has to be differentiated from Ehlers-Danlos syndrome where there is joint laxity in addition to the skin changes.  Pathology not exactly known. Few studies has shown that serum copper was low and urinary excretion high, consistent with the theory that low serum copper level produces a low elastase inhibitor substance with increase distruction of elastic fibers.

 Fig. 2.23: Cutis laxa. Child with loose skin folds, joint and ligamentary laxity

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SCLERODERMA (Figs 2.24 A and B) DEFINITION  Definition: It is a chronic disorder of idiopathic origin characterized by fibrosis affecting dermis and arteries of lung, kidney and GIT. The ANA is positive against topoisomerase 1 (SCL70) and centromere suggesting autoimmune etiology.  Mainly of two-types—systemic sclerosis (diffuse involvement), localized scleroderma (morphea). SYSTEMIC SCLEROSIS  It starts with edematous phase before fibrosis sets in. Loss of subcutaneous tissue in the face results in small stoma, skin ulceration over pressure points, loss of tissue at fingertip giving rise to ulceration especially when raynauds phenomenon is severe.  Distal phalanges exhibit acro-osteolysis, sclerodactyly.  Other chronic changes include epidermal thinning, hair loss and decreased sweating.  Systemic involvement: Respiratory- includes arterial and interstitial involvement, which may lead to right sided heart failure. Renal involvement leads to renal arterial disease leading to hypertension, Heart- cardiac fibrosis, arrhythmias, and ventricular hypertrophy.  CREST syndrome- refers to Calcinosis, Raynaud’s phenomenon, Oesophageal involvement, Sclerosis of the skin and telangiectasis. DIGNOSTIC CRITERIA  Major criterion: Proximal scleroderma- typical sclerodermatous skin changes (tightness, thickening and nonpitting induration excluding localized forms of scleroderma) area involving proximal to metacarpophalangeal or metatarsophalangeal joints.

A

B

Figs 2.24A and B: Systemic sclerosis (A) Hardening of skin with pigmentation, loss of nasolabial folds and expression less face. (B) Comparison of skin laxity with her mothers. Hardened skin is difficult to lift

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 Minor criteria: Sclerodactyly, scleromatous skin changes limited to digits. Digital pitting scars resulting from digital ischemia. Bibasillary pulmonary fibrosis non attributable to pulmonary lung disease. (The diagnosis of scleroderma requires the presence of the major criterion or two of the three minor criterions. Arthritis rheum 1980;23:581). TREATMENT  No specific treatment. Immunosuppressive agents like corticosteroid and methotrexate in early stage of disease may be helpful. Physiotherapy and occupational therapy improves flexion contraction in selected cases.

TINEA CORPORIS (Fig. 2.25) DEFINITION  It is fungal infection of skin caused by dermatophytes, namely M.canis, T.mentagrophytes, T.tonsurans and T.rubran.  It consists of one or several erythematous patches. These patches may have a popular, scaly, annular border and a clear center. PATHOGENESIS  The dermatophytes invades the superficial layer of epidermis, the stratum corneum. The exact mechanism of the inflammation is not known, but toxin released by dermatophytes are responsible for initiating inflammatory response. DIAGNOSIS  DIAGNOSIS is confirmed by KOH examination of scraping of thin scales obtained from border of the lesion.

Fig. 2.25: Tinea corporis. Presence of circinate patch with prominent papulo-vesicular margins

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TREATMENT  Tinea corporis is treated by application of topical antifungal cream. Topical terbinafine produces clinical and mycological clearing within one week. Other topical antifungal used are ciclopirox, clotrimazole, ketokonazole, econazole, miconazole, etc. The cream has to be applied twice day for atleast 4 to 6 weeks. ADVISE AND FOLLOWUP  Parents are explained that these fungus are present in soil and animals; one must trace the source of infection and other family members can be prevented to contract infection. Cream application should cover whole of the lesion plus one centimeter border beyond it. Skin has to be kept dry and contact with pets are avoided.

URTICARIA (Fig. 2.26)  Urticaria is a common skin disorder that affects 15 to 20 percent of population. It is characterized by transient edematous pink papules and plaques that are called wheels.  Urticaria of less than 6 weeks duration is called as acute, while that lasting more than 6 weeks it is termed as chronic urticaria.  Mechanism • Most common is the IgE dependent hypersensitivity, which is the most common. Here the sensitised mast cell or basophiles releases mediators such as histamine after exposure to antigen. Example is urticaria caused by food, drugs like penicillin, animal dander’s etc. • Urticaria may also be due to direct mast cell degranulation, e.g. Medications like opiates, curare and radio contrast media. • Urticaria is also seen in disorder of complement system, e.g. vasculitis, serum sickness, collagen vascular disease.  Clinical features • The most characteristic features of the wheels is the transient, fleeting nature. Individual lesion may last few minutes to hours, but rarely longer than 24 hours. If the single wheel persists for more than 24 hours the diagnosis should be revised. • The lesions are erythematous, pale center and with pruritis. They may be localized or generalized; circular, annular or serpigenous and ranges from few millimeter to several centimeters. • Some time large wheels and diffuse swelling occurs representing involvement of deep dermis. This is called as angioedema. Mostly affects face and extremity. Systemic involvement includes dizziness, swelling in the throat, difficulty in breathing, wheezing, nausea, vomiting abdominal pain and diarrhea.  Diagnosis • Diagnosis is straightforward with history and physical examination. The real difficulty lies in detecting the cause. In children it is usually the infections that to viral upper respiratory infection. Bacterial, fungal and parasitic may be the triggering factors.

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Fig. 2.26: Urticaria

•

Physical factors like cold, heat, vibration, sunlight and water may provoke rashes. Dermatographism is the most common physical urticaria, refers to wheel, which appears after stroking of skin.  Treatment • Elimination of the cause and prevention of exposure again. • H-1 receptor antagonist like hydroxyzine and diphenhydramine are very effective but are sedating. • Newer generation H-1 blockers like loratidine, fexofenadine and cetrizine are effective. • Addition of H-2 antagonist like cimitedine, ranitidine and femotidine to H-1 receptor antagonist may be useful. • Corticosteroid and subcutaneous epinephrine are reserved for severe attacks with laryngeal edema.

DERMATOGRAPHISM (Fig. 2.27)  The ability to write on skin is termed as Dermatographism. It is seen as an isolated disorder or with chronic urticaria and physical urticaria like cholinergic or cold urticaria.  It occurs in one percent of adolescents and it occurs as wheel and erythema following minor stoking or pressure on the skin. The wheel reaches maximum size in 6 to 7 minutes and persists for 10 to 15 minutes. It is due to reflex vasoconstriction.  In 50 percent cases it is related to IgA-dependent mechanism.  When wheel is seen in comatose children, e.g. encephalitis, meningitis, and drug over dosage it is termed as tache cerebrale.  Dermatographism may persist for years but most patient shows spontaneous regression within 2 years.

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Fig. 2.27: Dermatographism

DERMATOFIBROMA* (Fig. 2.28)  These are benign dermal tumors may be pedunculated, nodular or flat usually well circumscribed. The overlying skin is usually hyperpigmented, may be shiny or keratotic.  Dermatofibroma ranges in size from 0.5 to 10 mm arise most frequently on the limbs and are usually asymptomatic but occasionally are pruritic.  The cause of tumor is unknown, but trauma such as insect bite or folliculitis appears to induce reactive hyperplasia.  The differential diagnosis includes epidermal inclusion cyst, juvenile xanthogranuloma, neurofibroma.  Treatment: They can be excised or left intact according to patient choice. They usually persist indefinitely but occasionally involute spontaneously.

 Fig. 2.28: Dermatofibroma

CONGENITAL MELANOCYTIC NEVUS (Figs 2.29 A to C)  Congenital melanocytic nevi are present in approximately one percent of newborn infants. The nevi is characterized by size: Giant congenital nevi are more than 20 mm in diameter (adult size), small congenital nevi less than 2 mm in diameter, intermediate are in between these two sizes.

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A

B

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Figs 2.29A to C: Giant nevus (A) (B) (Neurocutaneous melanosis). Note the large bathing trunk nevi and small lesion elsewhere especially head and scalp. Photographs by Dr Pallabh Chhaterjee, Kolkata (C) Note the Giant hairy nevus over back and chest

 Small congenital nevus seen over lower trunk, upper back shoulders, chest and proximal limb. The lesions are flat, elevated, verrucous and may be of various shades brown, black or blue. The malignancy potential of small nevi is approximately 15 percent.  Giant congenital pigmented nevus seen in ( 5 g/100 ml (PCV>15%), (2) pallor in one twin and plethora in the other, (3) inter-twin birth weight difference > 15 percent. Medical care of twins after birth is directed towards problem related to anemia, polycythemia and hydrops.

NONIMMUNE HYDROPS (Figs 3.30A and B)  Definition: Hydrops fetalis is a severe, life-threatening problem of severe edema (swelling) in the fetus and newborn. It is also called hydrops. There are two types of hydrops: • Immune - results when the mother’s immunesystem causes breakdown of red blood cells in the fetus. This is the most dangerous problem of blood group incompatibility between the mother and baby. • Non-immune - the most common type; can result when diseases or complications interfere with the baby’s ability to manage fluid.  Cause: Hydrops develops when too much fluid leaves the bloodstream and goes into the tissues. Many different diseases and complications can cause hydrops, including the following:  Immune hydrops may develop because of Rh disease in the mother. When an Rh negative mother has an Rh positive baby, the mother’s immunesystem sees the baby’s Rh positive red blood cells as “foreign.” When the mother’s antibodies attack the foreign red blood cells, they are broken down and destroyed, resulting in anemia. Hydrops can develop as the baby’s organs are unable to compensate for the anemia. The heart begins to fail and large amounts of fluid build up in the baby’s tissues and organs.  Non-immune hydrops includes all other diseases or complications that may interfere with the baby’s ability to manage fluid. There is no one mechanism to explain non-immune hydrops. Some of the diseases or complications that are often associated with hydrops include the following: • severe anemias • congenital infections (infections present at birth) • heart or lung defects • chromosomal abnormalities and birth defects • liver disease  In addition to a complete medical history and physical examination, diagnostic procedures for hydrops fetalis may include:

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Figs 3.30A and B: (A) Non immune hydrops. (B) Abortus dipicting the picture of hydrops. Photograph courtesy: Dr Sarita Agrawal, Bilaspur

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•

ultrasound—a diagnostic imaging technique which uses high-frequency sound waves and a computer to create images of blood vessels, tissues, and organs. Ultrasounds are used to view internal organs as they function, and to assess blood flow through various vessels. • fetal blood sampling—done by placing a needle through the mother’s uterus and into a blood vessel of the fetus or the umbilical cord. • amniocentesis—withdrawing some of the amniotic fluid for testing.  Treatment of hydrops depends on the cause. During pregnancy, hydrops may be treatable only in certain situations. Management of hydrops in newborn babies may include: • help for respiratory distress using supplemental oxygen or a mechanical breathing machine • removal of excessive fluid from spaces around the lungs and abdomen using a needle medications to help the kidneys remove excess fluid.

EPIGNATHUS (Figs 3.31A and B)  Definition: A teratoma that arises from the oral cavity or pharynx.  Incidence: Two percent of all pediatric teratomas occurs in nasopharyngeal area (including oral, tonsillar and basicranial area).  Pathology: Most of the tumors arise from the sphenoid bone. Some arise from the hard and soft palate, the pharynx, the tongue and jaw. From their site of origin the tumor grows into the oral cavity or nasal cavity or intracranially. Most tumors are benign. Histologically, they consist of tissues derived from any of the three germinal layers. Obstruction of the mouth is responsible for polyhydramnios.  Associated anomalies: Six percent of the tumors have associated anomalies. They include cleft palate, multiple facial hemangiomas, branchial cysts, hypertelorism, umbilical hernia and congenital heart defect.

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Figs 3.31A and B: Epignathus. (A) Extremely premature baby with epignathus. (B) Full term baby with the mass from the hard palate

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 Diagnosis: Antenatal sonography—a solid tumor emanating from the fetal oral cavity is suggestive of this condition. Calcification and cystic component can be visualized.  Prognosis: It depends on size of the tumor and involvement of vital structures. Polyhydramnios is associated with poor prognosis. Major cause of death is asphyxia because of airway obstruction.

SACROCOCCYGEAL TERATOMA (Fig. 3.32)  It is the commonest teratoma presenting in the neonatal period with the majority arising in females.  They are large and tend to be protrude from the space between the anus and the coccyx (Fig. 3.32). The lesion is usually covered in the skin. The tumor may extend up into the pelvis and a large retrorectal component is palpable.  It may be both solid and cystic in nature. It may contain tissues representing all three germ cell layers.  The condition may be diagnosed in utero or at birth. Large tumor may give rise to dystocia and cesarean delivery may be required. Malignancy may vary from 10 to 50 percent. Alfafetoprotein is a useful tumor marker. Elevated level at birth may decline following the excision.  Treatment is excision in the first few days of life.

Fig. 3.32: Sacrococcygeal teratoma. Photograph courtesy: Dr Ramesh Bhatt, KMC Manipal

OPHTHALMIA NEONATORUM (Fig. 3.33)  Ophthalmia neonatorum due to N.gonorrhoeae is classically an acute purulent conjunctivitis that appears from 2 to 5 days after birth.  Infants who become infected in-utero may have symptoms at or shortly after birth. Typically early in the illness, tense edema of both lids develops, followed by profuse purulent conjunctival exudates.  If treatment is delayed, the infection progresses beyond the superficial layers of the eye to involve the subconjunctival connective tissue of the palpebral conjunctivae and the cornea. Infection of the cornea can lead to Fig. 3.33: Ophthalmia neonatorum. ulceration, perforation, or rarely panophthalmitis. In some Photograph courtesy: Dr Abhijeet instances it may result in loss of the eye. Saha and Dr Prerna Batra, MGIMS,  Isolation of N.gonorrhoeae from the exudates by culture Sevagram is the diagnostic gold standard. Ceftriaxone is the drug of choice.

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EAR ANOMALIES (Figs 3.34A to E) ABNORMAL PINNA Abnormality of pinna varies considerably. Fig. 3.34A, shows abnormality in shape of the pinna. This type of minor abnormality may require surgery for cosmetic reasons. MALFORMED EAR-LOP EAR Fig. 3.34B, an unusually prominent or lop ear results from lack of bending of the cartilage that creates the antihelix. The baby had other features of Townes syndrome. Application of firm framework or otoplasty may be required for cosmetic correction. Microtia indicate subtle abnormalities of the size, shape, and location of the pinna and ear canal, or major abnormalities with only small nubbins of skin and cartilage and absence of the ear canal opening. They are more anterior and inferior in placement than normal ears. Treatment includes cosmetic reconstruction. Severe cases may require prosthetic ear. PREAURICULAR SKIN TAG AND MALFORMED PINNA Fig. 3.34C, preauricular accessory skin tag has incidence of 1-2/1000. It can be removed for cosmetic reasons by simple ligation if they are attached by a narrow pedicle. If the pedicle is broad based or contains cartilage surgical correction may be required.

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C

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Figs 3.34A to E: Malformation of ear. (A) Abnormal pinna. (B) Unusually prominent ear or lop ear. (C) Preauricular skin tag with abnormal pinna. (D) Preauricular skin tag, malformed pinna and absent auditory canal. (E) Preauricular skin tag with large tragus. Photograph courtesy: Dr Ramesh Bhatt, KMC Manipal

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PREAURICUALR SKIN TAG, MALFORMED PINNA AND ABSENT EXTERNAL CANAL Fig. 3.34D, shows malformed or misshapen auricle associated with meatal atresia, the absence of bony canal. They are commonly associated together in a variety of congenital conditions and syndromes. They may present as unilateral or bilateral problems. Surgical reconstruction of pinna and or fashioning of external meatus may be required. PREAURICUALR SKIN TAG AND LARGE TRAGUS Fig. 3.34E, shows minor auricular abnormality—a skin tag with a narrow pedicle and large tragus. REFERENCES 1. Carr.JA, Hodgman JE. Relationship between toxic erythema and infant maturity, Am.J.Dis.Child 1966;112:129. 2. Cordova A. The Mongolian spot: A study of ethnic differences and a literature review. Clin. Pediatr: 1981;20:714. 3. Aler JC, Holmes LB. The incidence and significance of birthmarks in a cohort of 4,641 newborn. Pediatr Dermatol 1983;1:58. 4. Farquhar JW. The child of the diabetic women. Arch Dis Child 1959;34:76. 5. Torpin R. Amniochorionic mesoblastic fibrous strings and amniotic band: Associated constricting fetal malformation or fetal death. Am J Obstet Gynecol 1965;91:65. 6. Higginbottom MC, John KL et al. The amniotic band disruption complex: Timing of amniotic rupture and variable spectra of consequent defects. J Pediatr 1979;95:544. 7. Koltmier PK. Birth Trauma, Pediatric Surgery 4th edn., Chicago, Year Book Medical Publisher 1986;23037.

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Endocrinology

GYNECOMASTIA (Fig. 4.1)  Gynecomastia is defined as the visible or palpable development of breast tissue in boys and men. There are four types of gynecomastia.  Type I: (Pubertal gynecomastia or benign adolescent breast hypertrophy). It is common benign condition of enlargement of breast tissue ranges between 60 and 70 percent seen in adolescent population. It is firm tender subareolar mass between 1 and 5 mm in diameter. This is painful swelling especially obvious during changing of cloths. It spontaneously resolves within 2 years.  Type II: (physiologic gynecomastia without evidence of underlying disease or evidence of organic disease, including the effect of specific drugs). There is generalized nontender enlargement of breast. It is important for treating physician to differentiate physiological enlargement from pathological enlargement. Careful history, time of onset, associated systemic disease, history of drug ingestion. Good clinical examination includes height, weight, blood pressure, breast size and tanner staging of breast and genitals.

 Fig 4.1: Gynecomastia in 12-year-old boy. If the breast tissue is pinched between thumb and forefinger and moved upwards towards nipple a feeling of firm, rubbery feeling of glandular tissue underneath nipple and areola is seen in gynecomastia

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Common causes of type II gynecomastia— 1. Idiopathic 2. Familial 3. Specific illness/syndromes 4. Klinefelter’s syndrome 5. Male pseudohermaphroditism 6. Testicular feminization syndrome 7. Tumors—teratoma, hepatoma, feminising syndrome tumors 8. Leukemias 9. Hemophilia 10. Leprosy 11. Hyper or hypothyroidism 12. Miscellaneous drugs—amphetamines, anabolic steroids, cimetidine, clomephine diazepam, estrogens, digitalis, insulin, testosterone.  Type III: General obesity simulating gynecomastia.  Type IV: Pectoral muscle hypertrophy. TREATMENT  Pubertal gynecomastia less than 4 cm in diameter requires no therapy except reassurance. It resolves spontaneously without treatment and in 75 percent cases within 2 years and in about 95 percent cases within 3 years.  If enlargement is striking macrogynecomastia producing psychological and emotional problems medical and surgical treatment can be considered.  Drugs are rarely used due to poor success rate. Drugs with antiestrogenic effect like tamoxifen, arometase inhibitor like testolactone are often used.  Surgery—Transareolar reduction mamoplasty and liposuction. Indications are: • For persistent macrogynecomastia of four years or longer duration. After four years breast tissue shows fibrosis and hyalinization, which is frequently irreversible. • For cosmetic reasons.

IDIOPATHIC PRECOCIOUS PUBERTY (Fig. 4.2) DEFINITION Precocious puberty is generally defined as the onset of secondary sexual characteristic before age of 8 years in female and 9 years in male. Idiopathic sexual precocity is 10 times more common in girls than in boys. However, structural CNS abnormality can be demonstrated in 25 to 75 percent of boys and in some girls with central precocious puberty. CLINICAL PICTURE Sexual development can occur at any age and breast enlargement is the first sign and pubic hairs appear late may be followed by maturation of external genitalia, axillary hairs. Menstruation

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 Fig. 4.2: Idiopathic precocious puberty. Patient aged 6 years with breast enlargement. Osseous maturation advanced. Estrogen assay was normal. Intelligence was normal for age

is seen quite early in these patients. The cycles are anovulatary and irregular initially but pregnancy is seen in some cases as early as 5.5 years. There is advanced bone maturation as a result there is premature fusion of epiphysis resulting into short stature. Mental development is normal for age. INVESTIGATIONS Serum estradiol concentration is lower or even absent initially as in normal puberty. Immunometric assay of LH offers greater diagnostic sensitivity using random blood sample. It is positive in 50 to 70 percent of girls with precocious puberty. Osseous maturation is advanced more than 2 to 3 SD. Pelvic USG reveals enlargement of ovaries and uterus. CT and MRI reveals physiological enlargement of pituitary gland as seen in normal puberty. TREATMENT Long acting GnRH analogs like leuprolide 0.3 mg/kg IM every month. Suppression of pituitary gonadotrophin occurs after 1-2 months. This drug can be withdrawn at normal expected age of puberty.

CUSHING SYNDROME (CS) (Fig. 4.3) It is caused by abnormally high blood levels of cortisol or other glucocorticoids. It can be iatrogenic or due to endogenous cortisol secretion either by adrenal tumor or to hypersecretion of ACTH from pituitary. CAUSES Excess of glucocorticoids in children is uncommon; and most of CS is iatrogenic. In infants adrenocortical tumor is responsible for

 Fig. 4.3: Cushing syndrome. General obesity, round, plethoric “moon” face, and increased skin folds.

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CS and in children above 7 years important cause is Cushing’s disease, i.e. excess of ACTH secreted by pituitary adenoma which causes bilateral adrenal hyperplasia. CLINICAL PICTURE In young children moon facies, double chin, buffalo hump, obesity, musculinization, hypertrichosis on face and trunk, pubic hair, acne, clitorial enlargement, impaired growth. In older children, growth failure, obesity, purplish striae, delayed puberty, weakness, headache and emotional liability occur. LABORATORY FINDINGS includes polycythemia, lymphopenia, eosinopenia, abnormal glucose tolerance, lack of diurnal rhythm, elevated urinary and serum cortisol, osteoporosis, variable bone maturation, and suppressed growth hormone. MRI brain reveals pituitary adenoma. TREATMENT Surgical removal of adenoma/ carcinoma. Total adrenalectomy can cause postoperative pituitary tumor expansion and elevated ACTH and an enlarge sella turcica (Nelson syndrome). Additional therapies consist of transphenoidal pituitary microsurgery; radiation and cyproheptadine may block release of ACTH. PROGNOSIS  Prognosis depends on etiology, method of treatment and severity of glucocorticoids excess. Complications such as avascular necrosis of femoral head, hypertension, and posterior capsular cataract can be seen.  In ACTH dependent CS (Cushing’s disease) surgery may often lead to Nelson syndrome.  Catch-up growth is restored after surgery, but poor prognosis is seen in-patient with adrenal carcinoma.  Follow-up—In patient undergone bilateral adrenectomy steroid therapy has to be given life long. Hydrocortisone 10-20 mg /m2/d three times day, fludrocortisone 0.05 mg-0.2 mg/d. In patient recovering from iatrogenic CS early morning cortisol level is assessed to see the adrenal function.

CONGENITAL HYPOTHYROIDISM (Figs. 4.4A and B)  Thyroid hormone has important roles in embryogenesis and fetal maturation. Deficiency of iodine in the diet of mothers in particular areas causes maternal hypothyroxinemia leading to neonatal hypothyroidism and defects in IQ. Thus, iodine deficiency is the cause of endemic cretinism but other factors also aggravates it like, dietary goitrogen such as (thyocynates), selenium deficiency and autoimmune hypothyroidism.  Deficiency of thyroid hormone is believed to have been present at or before birth. Prompt diagnosis is essential as delay in treatment can lead to irreversible brain damage.

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B

Figs 4.4A and B: Congenital hypothyroidism. (A) 6 month old child, hypotonic with dry skin, low-pitched hoarse cry, low body temperature, macroglossia and umbilical hernia. (B) X-ray wrist for bone age. No carpel bone ossification center is visible

 The incidence of congenital hypothyroidism is 1 in 3500 deliveries. An Indian population study quote an incidence of 1 in 2800-4500 especially in Western states. Congenital hypothyroidism is more common in Down syndrome (1:128). ETIOLOGY  The commonest etiology is thyroid ectopia and dysplasia resulting from maldescent in early gestation. Majority cases have thyroid dysgenesis which is sporadic in inheritance, hence no chance of repeating in next pregnancy. There is no goiter in such cases. Female preponderance is quoted for thyroid dysgenesis. Some time there is inborn error in thyroid hormone synthesis, this autosomal recessive condition have 5 percent chance of recurrence in subsequent siblings.  Penred syndrome comprising of sensorineural deafness and goiter has positive perchlorate discharge. It is due to defect in a sulphate transport protein common to the thyroid gland and the cochlea. It contributes to T4 synthetic defects leading to hypothyroidism. CLINICAL FEATURES Usually not presents at birth and appears gradually over about 6 weeks. In 5 percent cases exhibit clinical features in first week of life. Early manifestation includes lethargy, inactivity, hypotonia, periorbital edema, large fontanels, feeding difficulty, cutis marmuratus, respiratory distress, thermal instability, poor or hoarse cry, and constipation. After one week of life prolong physiological jaundice is an indication of congenital hypothyroidism. Classical clinical picture develops only after six weeks. This includes typical faces narrow forehead, puffy eyelids, thick dry and cold skin, coarse hair, large tongue, umbilical hernia, bradycardia, anemia, and wide cranial sutures. Enlarge posterior fontanel > 1 cm.

KOCHER-DEBRE-SEMELAIGNE SYNDROME (Figs 4.5A to C) Affected children may have athletic because of pseudohypertrophy, particularly of the calf muscle. These muscles are hypotonic. Its pathogenesis is unknown, nonspecific histochemical and ultrastructural changes seen on muscle biopsy returns to normal after treatment. Boys are more prone to develop this syndrome.

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Figs 4.5A to C: (A) Hypothyroid boy with generalized pseudohypertrophy of muscles athletic appearance (Kocher-Debre-Semelaigne syndrome). (B) Acquired hypothyroidism in 15-year-old girl later confirmed as autoimmune thyroiditis. (C) Pubertal enlargement of thyroid gland

LABORATORY DIAGNOSIS Estimation of T4 and TSH level decides the presence or absence congenital hypothyroidism. A TSH level of above 20 IU and low T4 levels are indicative of congenital hypothyroidism. This has to be repeated after one month. T4 comes to normal within one month but TSH takes 3 months or more to normalize. In later ages level has to be matched with the age related references. X-ray of knee and ankle reveals delayed bony maturation. Ossification of calcaneum and talus appears at 26–28 weeks, distal femur at 34–36 weeks, proximal tibia at 34–36 weeks. Hence, absence of these centers indicates intrauterine thyroid hormone deficiency. Some time epiphyseal center may be fragmented called as epiphyseal dysgenesis. TREATMENT All hypothyroid infants with or without goiter should be treated promptly by thyroxine. • Dose schedule of thyroxine • 0-6 month 10-15 microgm/kg/d • 6-12 month 6-8 microgm/kg/d • 1-5 year 5-6 microgram/kg/d • 6-12 year 4 microgm/kg/d T4 level should be maintained at 12-13 microgm/dl for first year and 10 microgm/dl thereafter. TSH level should be 24 hours after birth

90% survival) None in 3rd trimester Left

Detection at < 24 weeks Above diaphragm (30% survival) Present in 2nd trimester Right

Normal/improved on ventilation >7.2 (100% survival)

Unresponsive 1 mg%) the baby (or child) is kept on bladder drainage (suprapubic or urethral) and intravenous antibiotics. If it improves on bladder drainage, VCUG and valve fulguration is done. In about 15 percent cases no improvement occurs. These patients are subjected to bilateral ureterostomies with plan for valve fulguration and urinary tract reconstruction later.

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The prognosis is determined by a number of factors such as renal functions at the time of presentation, improvement of renal functions on bladder drainage, presence and grade of vesicoureteric reflux, intercurrent infections and adequacy of fulguration. It is important to understand that the obstruction to the bladder outlet is a chronic one and occurs at a time when the urinary tract musculature is undergoing developmental changes. Therefore, many irreversible changes result in the bladder muscles that persist after an adequate fulguration. These have a bearing on the final outcome and may require additional therapy (pharmacological or surgical) to bring down the urinary tract pressure and provide complete drainage to the bladder.

BLADDER EXSTROPHY—EPISPADIAS (Figs 5.32, 5.33A and B) The exstrophy-epispadias complex comprises a spectrum of congenital abnormalities that includes classic bladder exstrophy, epispadias, cloacal exstrophy, and several variants. FREQUENCY Prevalence of classic bladder exstrophy is 3.3 per 100,000 births; male epispadias occurs in 1 in 117,000 births, female epispadias in 1 in 484,000 births, and cloacal exstrophy in 1 in 200,000400,000 births. PATHOLOGY Abdomen: Classic bladder exstrophy: The bladder is open on the lower abdomen, with mucosa fully exposed through a triangular fascial defect. Urine can be seen dribbling from the ureteric orifices, which can be identified on close examination. The distance between the umbilicus and anus is foreshortened. Rectus muscles diverge distally, attaching to the widely separated pubic bones. Indirect inguinal hernias are frequent (>80 percent of males, >10% of females) due to wide inguinal rings and the lack of an oblique inguinal canal.

Fig. 5.32: Bladder extrophy and epispadias in male

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GENITALIA Classic bladder exstrophy and Epispadias (male): The phallus is short and broad with upward curvature (dorsal chordee). The glans lies open and flat like a spade, and the dorsal component of the foreskin is absent. The urethral plate extends the length of the phallus without a roof. The bladder plate and urethral plate are in continuity. The anus is anteriorly displaced. MUSCULOSKELETAL Musculoskeletal abnormalities occur mostly in classic bladder exstrophy and more severe variants. The pubic symphysis is widely separated. Divergent rectus muscles remain attached to the pubis. External rotation of the innominate bones results in a waddling gait in ambulatory patients but does not appear to result in orthopedic problems later in life. EMBRYOLOGY Failure of mesenchyme to migrate between the ectodermal and endodermal layers of the lower abdominal wall leads to instability and rupture of the cloacal membrane leading to this complex of infraumbilical anomalies. PRENATAL ULTRASONOGRAPHY Antenatal ultrasound findings suggestive of exstrophy-epispadias complex include repeated failure to visualize the bladder, low-set umbilical cord, lower abdominal wall mass and abnormal genitalia. POSTNATAL MANAGEMENT Patients typically appear as term infants. One should look for associate spinal and cardiovascular anomalies that may be associated with more complex variant, i.e. cloacal exstrophy. Baseline ultrasound examination of the kidneys is recommended for all patients with exstrophy. A clean plastic wrap should be placed over the bladder plate. Moistened or impregnated gauze should be avoided, as it is irritating to the delicate bladder mucosa. Antibiotic therapy should be started after delivery and continued through the early postoperative period. Though still evolving, operative management is the accepted treatment of bladder exstrophy. Left untreated, the continuous smell of urine makes such patients socially unacceptable. Also there is a risk of malignant transformation of the bladder mucosa. Reconstruction of exstrophy-epispadias complex remains one of the greatest challenges facing the pediatric urologist. Many modifications in surgical procedures have improved the outcome for these patients, but the goal to make the child grow into a dry, fertile and happy adult is yet to be fulfilled. Surgical technique classically comprises of staged functional closure for classic bladder exstrophy. Initial bladder closure is completed within 72 hours of birth. If delayed, pelvic osteotomies are required to close the abdominal wall. Epispadias repair with urethroplasty at age 12-18 months allows enough increase in bladder outlet resistance to improve the bladder capacity. Bladder neck reconstruction at age 4 years allows continence and correction of vesicoureteral reflux.

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Recently single stage complete primary repair is being tried with some success. Urinary diversion may be required for some cases. PROGNOSIS Evidence indicates that many exstrophic bladders do not function normally after reconstruction and may deteriorate over time. Some studies have reported continence rates of 75 to 90 percent after staged reconstruction in classic exstrophy, but more than one continence procedure are usually required (e.g., bladder neck reconstruction, bladder augmentation, bladder neck sling, artificial urinary sphincter). Many of these patients require life long clean intermittent catheterization (CIC) through the urethra or a continent stoma because they are unable to void spontaneously to completion. VARIANTS Among the variants of the above-described classic bladder exstrophy are continent and incontinent hypospadias, pubovesical cleft and covered exstrophy. A severe variant of bladder exstrophy is cloacal exstrophy that occurs in 1 in 200,000400,000 births. Patients are often preterm. Nearly all patients have an associated omphalocele. The bladder is open and separated into 2 halves, flanking the exposed interior of the cecum. Terminal ileum may prolapse as a “trunk” of bowel onto the cecal plate. The anus is absent. The phallus is generally quite small and bifid. Often the testis may not be palpable and gender assignment becomes difficult. As many as 95 percent of patients have myelodysplasia. This is a far more complex condition to treat. Result of surgery remains poor.

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B

Figs 5.33A and B: (A) Cloacal exstrophy with limb anomalies (B) Meningocele in the same patient

RHABDOMYOSARCOMA (RMS) (Figs 5.34A and B) Rhabdomyosarcoma is the most common type of soft tissue sarcoma found in children. It is still a rare cancer overall, accounting for about 3.5 percent of all childhood cancers. Over 85 percent of all rhabdomyosarcomas occur in infants, children, and teenagers. However, Asian children have a lower annual incidence than do white children.

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PATHOLOGY The head and neck are the most frequent (35-40%) sites of origin, followed by the genitourinary tract, extremities, trunk, retroperitoneum, and uncommon regions (e.g., intrathoracic, GI tract, perianal and anal regions). Although the tumor is believed to arise from primitive muscle cells, tumors can occur anywhere in the body except bone. Rhabdomyosarcoma is divided into 5 major histologic categories: embryonal, alveolar, botryoid embryonal, spindle cell embryonal, and anaplastic. Embryonal rhabdomyosarcoma is the most common subtype observed in children, accounting for approximately 60 percent of all cases in this age group. STAGING The TNM staging system uses a preoperative evaluation to stage the tumour:  Stage I—tumors involving the area near the eye, the head, neck, and genitourinary tract (except the prostate and bladder). The tumor is localized, meaning that the tumor has not spread to other areas of the body.  Stage II—small, localized tumors less than 5 cm in any site not in stage I. There are no tumor cells in the surrounding lymph nodes.  Stage III—localized tumor at any site not included in stage I that is larger than 5 cm and/or has spread to surrounding lymph nodes.  Stage IV—disease that has spread to other areas of the body at the time of diagnosis. PATHOGENESIS Rhabdomyosarcomas usually have some type of chromosomal abnormality in the cells of the tumor, which are responsible for the tumor formation. The cause of these chromosomal abnormalities is unknown. PRESENTATION RMS usually manifests as an expanding mass; symptoms depend on the location of the tumor. Pain may be present. If metastatic disease is present, symptoms of bone pain, respiratory difficulty (secondary to lung nodules or to pleural effusion), anemia, thrombocytopenia, and neutropenia may be present. Disseminated rhabdomyoblasts in the bone marrow may mimic leukemia. Typical presentations by the location of nonmetastatic disease are as follows:  Orbit—Proptosis or dysconjugate gaze  Paratesticular—Painless scrotal mass  Prostate—Bladder or bowel difficulties  Vagina—Protruding polypoid mass (botryoid, meaning a grapelike cluster)  Extremity—Painless mass  Parameningeal (ear, mastoid, nasal cavity, paranasal sinuses, infratemporal fossa, pterygopalatine fossa)—Upper respiratory symptoms or pain.

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Figs 5.34A and B: (A) Rhabdomyosarcoma of the tongue. (B) after treatment Photograph courtsey: Dr. Prof Bhudwani (Bhopal)

DIAGNOSIS The initial diagnostic workup must address two basic issues. The nature of the primary disease is determined by a surgical biopsy and extent by either CT or MRI. Next, the clinician must evaluate the patient for locoregional or metastatic disease. This evaluation is accomplished by performing a battery of adjunctive studies, including bone marrow biopsy, chest CT, and bone scanning. TREATMENT Treatment in patients with RMS involves a combination of surgery, chemotherapy, and radiation therapy. PROGNOSTIC FACTORS 1. The site of origin: Head and neck rhabdomyosarcoma affecting the orbit and nonparameningeal area have a prognosis more favorable than that of patients with tumors in other sites in the body. 2. Tumor burden: Individuals with tumors smaller than 5 cm have a better prognosis when compared with those with larger tumors. 3. Regional and distant metastasis: Regional nodal involvement is a poor prognostic marker. 4. Age: Patients who are younger than 10 years have a better prognosis compared to older children. But infants tend to have a poorer prognosis again as they tolerate chemotherapy poorly. 5. Histology: The embryonal histology has a better survival than other types and the alveolar variety has the worst prognosis. 6. Residual disease: Patients without residual disease have a 90 percent 5-year survival rate. In patients with microscopic residual disease, survival decreases to 80 percent, and those with gross disease after surgery have a 5-year survival rate of 70 percent. 7. Biologic factors: Patients whose tumor cells have a DNA content 1.5 times higher than normal (hyperdiploid) have a better outcome than those with normal (diploid) or twice normal (tetraploid) DNA content.

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PROGNOSIS In patients with localized disease, overall 5-year survival rates have improved to >80 percent with the combined use of surgery, radiation therapy, and chemotherapy. However, in patients with metastatic disease, little progress has been made in survival rates, with a 5-year event-free survival rate 200 mV.  Tongue thrusting, sucking, swallowing seen. Wide mouth, wide spaced teeth and frequent drooling.

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Figs 7.15A and B: Angelman syndrome. Note happy disposition, wide mouth, wide spaced teeths

GENETIC ASPECTS There is microdeletion at chromosome 15 at 15q11-q13 seen in 60 percent cases. Few cases have paternal disomy for chromosome 15.

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DUCHENNE MUSCULAR DYSTROPHY (DMD) (Figs 7.16A to D) DEFINITION Duchenne muscular dystrophy is the most common hereditary neuromuscular disease affecting all race. INCIDENCE It is 1:3,600 live born infant boys. GENETIC It is inherited as X-linked recessive trait. DMD and Becker muscular dystrophy (BMD are variable phenotypic expressions of a gene defect at the Xp21 site. The abnormal gene product in both DMD and BMD is a reduced muscle content of the structural protein dystrophin. In DMD the dystrophin content is less than 3 percent of normal, and in BMD thee dystrophin content is 3 percent to 20 percent of normal. CLINICAL FEATURES  Gait disturbance is the early feature, onset always before age 5 years and is often before age 3.  Toe walking and frequent fall are typical complaints.  Proximal muscle weakness is sufficiently severe to cause difficulty in rising from floor and an obvious waddling gait. This is called as Gower’s sign. It is evident at age 3 and is fully expressed at age 5 to 6 yr. Calf muscle is hypertrophied.  There is learning disability and mild mental retardation.  Functional ability deteriorates after 8 yr, and after 9 children may requires wheel chair.  Scoliosis occurs in some children. The immediate cause of death is usually a combination of respiratory insufficiency and cardiomyopathy.

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Figs 7.16A to D: DMD. Note ths patient aged 6 yr exhibiting classical ‘GOWER’S SIGN’. The child needs to turn prone to rise, then uses his hands to climb up on his knees before standing, because of poor hip girdle fixation and or proximal muscle weakness. Any child continuing to do this after 3 yrs is likely to have a neuromuscular condition

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DIAGNOSIS  Before age 5 years the serum CK is 10 times the upper limits the rate of normal. The concentration then declines with age at an approximately 20 percent per year.  Mutation analysis is the standard for diagnosis, carrier detection, and fetal diagnosis. Iatrogenic deletion can be identified in 60 percent of affected boys and duplication in another 6 percent. Dystrophin analysis of muscle is useful to distinguish DMD from BMD. TREATMENT  There is neither a medical cure for the disease nor a method of slowing its progression. Quality of life can be improved by tackling complications.  Supportive therapy—cardiac, pulmonary support, vitamins, calcium, physiotherapy.  Myoblast transfer therapy—it is in experimental state.  Prednisolone, 0.75 mg/kg/d increases strength and function of muscle. It decreases the rate of apoptosis or programmed cell death of myotubules during ontogenesis, but long-term steroid use has its own disadvantage.

NEURAL TUBE DEFECT (Figs 7.17A to D) The term neural tube defects refers to a group of malformations including anencephaly, cephalocele and spina bifida. SPINA BIFIDA  Synonym- Spinal dysraphism, rachischisis, meningocele, meningomyelocele.  Definition- Spina bifida can be defined as a midline defect of the vertebrae resulting in exposure of the contents of neural canal.

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Figs 7.17A to D: (A) Pilonidal sinus. (B) Precoccegeal cleft. (C) Lipomeningocele. (D) Hypertrichosis over spina bifida occulta

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 Incidence- Spina bifida is the most common CNS malformation. In United States it is 1 in 1000 live birth, but there is continuous fall in the incidence due to periconceptional use of folic acid. The prevalence of NTD from different parts of India has been reported to vary from 0.5 to 11 per 1000 births.  Pathogenesis—Normally the rostral end of neural tube closes on 23rd day and caudal neuropore closes by 27th day. It is the result of failure of neural tube to close spontaneously between 3rd and 4th week of gestation.  Types—It encompasses a broad spectrum of abnormalities. Lesions are divided into ventral and dorsal. Ventral defects are extremely rare. These lesions are seen in lower cervical and upper thoracic vertebrae. Spina bifida Ventral

Dorsal

(Rare) Spina bifida occulta (15%)

(Common) Spina bifida aperta (85%) • Meningocele • Meningomyelocele

 Dorsal defect is by far the most common. They are subdivided into two spina bifida occulta 15 percent is characterized by small defect completely covered by skin. Most of the time the condition is asymptomatic and is detected incidentally at radiographic examination of the spine. Some time an area of hypertrichosis, pigmented or dimpled skin, or presence of subcutaneous lipoma. A dermal sinus connecting skin to vertebrae and to the dura mater may occasionally be seen.  Spina bifida aperta—is the most common, i.e. 85 percent of dorsal defect. It may be open or covered by a thin membrane. If the tumor contains purely meninges it is meningocele and if it contains neural tissue it is called meningomyelocele.  Associated anomalies—The two main categories are associated CNS defects and foot defect. The CNS defects consists of abnormality in posterior fossa called as Arnold-Chiari malformation type II. Dislocation of hip and foot deformity (club foot, rockerbottom foot).

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Figs 7.18A to C: (A) Lumbosacral Meningomyelocele (B) Thoracolumbar meningomyelocele (C) Cervical meningomyelocele

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 Clinical manifestation • These defects presents in axial skeletal with variable amount dermal covering depending on specific lesion. • Head is examined for presence of increased intracranial pressure by assessing fontanelles. Head size is important to rule out large size and lacunar skull (Leukenschadel) • Lower limb abnormalities includes club foot and limited range of movement. • Neurological examination depends on type and level of lesion. In higher lesion reflexes may be absent like knee, ankle and anal wink. Sensory impairment reflects the level of the lesion. • About 85 percent of the NTD occurs in isolation, and inheritance is multifactorial. There may be visible associated congenital anomalies like cleft lip and palate, imperforate anus and crytorchidism. • There are few conditions, which are associated with NTD. Like Chromosomal abnormalities especially trisomy 13 and 18 syndrome. Mutant gene (Meckels syndrome), teratogen exposure (alcohol, valproate, thalidomide).  Prenatal diagnosis • Maternal alpha fetoprotein (AFP) levels at 16 th weeks of gestational age is now standard. Elevated AFP for gestational age (>2.0 multiples of mean {MOM}) should prompt further investigation via high-resolution sonography to look for fetal anomalies. Elevated amniotic fluid AFP and acetylcholinesterase provides further support for the diagnosis. • Radiographic signs of open neural tube defect specifically include signs of the associated Arnold-Chiari malformation (a “banana sign” or flattened cerebellum and a transient frontal bone anomaly (a “Lemon sign”). USG can also demonstrate the level of the normal cord and placode. Fetal MRI can further define anatomy.  Preventive measures—all women of child bearing age should receive folic acid 0.4 mg/day (maximum daily requirement of folic acid is 0.4 mg).  For women who previously have given birth to an affected infant with a neural tube defect should receive folic acid 4.0 mg/day beginning one month prior to conception through 3 month of pregnancy.  Obstetrical management—The most important issue here is time and mode of delivery. Infants with spina bifida should be delivered at term. Preterm deliveries are considered in case when fetal ventriculomegaly and macrocrania is suspected. If the diagnosis is made in the second trimester the option for termination has to be offered to the patient. Vaginal deliveries may cause the trauma to neural tissues and exposes to bacteria of the birth canal.

SINCIPITAL MENINGOENCEPHALOCELE (Figs 7.19 A and B) Cranial meningoencephalocele are usually classified as Occipital, sincipital and basal. The sincipital type occurs around the dorsum of nose, the orbits and the forehead. Sincipital variant comprises 6.4 to 11.9 percent of cranial meningoencephalocele and is further subdivided into nasofrontal,

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Figs 7.19A and B: (A) Sincipital meningoencephalocele. (Photograph courtesy Dr Abhijeet Saha & Dr Prerna Batra Senior Lecturers in Pediatrics, MGIMS, Sevagram, Wardha. (B) Sincipital encephalocele in one month old female child.

nasoethmoidal and nasoorbital types. Clinically intracranial communication of this swelling is apparent due to presence of gentle pulsations in it and a positive cough impulse. CT scan is diagnostic. Operative intervention is by a combined neurosurgery and ENT team.

ANENCEPHALY (Figs 7.20A and B)    

Synonym—pseudoencephaly, extracranial disencephaly. Definition—Anencephaly is an anomaly characterized by the absence of cerebral hemisphere. Etiology—Multifactorial etiology. Pathology—Most of the cranial vault is absent. The frontal bone above the supraorbital ridge is absent, the parietal bones and the squamous part of occipital bones are absent. The crown of the brain is covered by vascular membrane called as “ area cerebrovasculosa”.  Antenatally it is diagnosed by USG as early as 12th to 13th weeks. Polyhydramnios is associated some time.  Prognosis—Almost fatal.  Obstetrical management—Termination of pregnancy can be offered to patient anencephaly infant are a potential source of organ for transplantation.

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Figs 7.20A and B: (A) Anencephalic baby with occipital encephalocele and attached placenta. (B) Anencephalic still born note the loss of cranial vault and peeping brainmatter

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INIENCEPHALY (Fig. 7.21) DEFINITION Iniencephaly is rare fatal neural tube defect characterized by involvement of occiput (inion) combined with rachischisis of cervical and thoracic spine with extreme retroflex ion of the head. It is an extremely rare condition. With an incidence in India is 1in 65,000. ETIOLOGY It has been reported in maternal syphilis and with sedative intake.

Fig. 7.21: Iniencephay stillborn. Note the extreme retroflexion of neck and rechischisis of cervico thoracic spine

DIAGNOSTIC CRITERIA  Imperfect foramina of the base of the skull, particularly at the level of foramen magnum.  Presence of spinal rachischisis.  Exaggerated lordosis of the spine. ASSOCIATED ANOMALIES Eighty four patient of iniencephalic infant have other associated anomalies, including anencephaly, cephalocele, absence of mandible, cleft lip and palate, cardiovascular anomalies, diaphragmatic hernia, single umbilical artery, omphalocele, gastoschisis, situs invertus. PROGNOSIS Almost fatal. OBSTETRICAL MANAGEMENT The option of termination of the pregnancy should be offered to the patient. If pregnancy is continued it may cause obstructed labor due to hyperextended head, hence cephalocentesis or embryotomy has to be done to avoid cesarean section.

MICROCEPHALY (Figs 7.22A and B) Most of the head growth occurs in the first two years of life and 80 percent of adult head size is achieved before the age of 5 years. This largely reflects the brain growth. DEFINITION Microcephaly is clinical syndrome characterized by a head circumference below 2 SD.

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Figs 7.22A and B: (A) Small sloping forehead with head circumference below 2 SD. Clinically patient was exhibiting features of spastic cerebral palsy (B) A patient with gross microcephaly and mental retardation

CLASSIFICATION Microcephaly is divided into two categories: (a) Microcephaly without associated anomalies and (b) Microcephaly with associated malformations like macrogyria, pachygyria, and atrophy of basal ganglia. Causes Familial—when present since birth and development is normal. Autosomal recessive condition— when it is associated with developmental delay. Congenital infections. Acquired—insult to the developing brain like perinatal hypoxia, hypoglycemia, meningitis, they are later associated with cerebral palsy and seizures.

AGENESIS OF CORPUS CALLOSUM (Figs 7.23A and B)  Dysgenesis of the corpus callosum is an anomaly that may occur in isolation or in association with other CNS or systemic malformations.  Dysgenesis of corpus callosum is usually a sporadic occurrence, although the incidence is increased in patients with trisomy 18, trisomy 13, and trisomy 8. Several familial cases have been reported.  Other anatomic abnormalities in patients include hydrocephalus; cephaloceles; and neuronal migration disorders such as lissencephaly, schizencephaly, gray matter heterotopias, pachygria, and polymicrogyria.  The clinical manifestations of callosal dysgenesis can be described under two headings: nonsyndromic and syndromic. • Nonsyndromic forms are the most common. An unknown, though probably small, proportion of patients are completely asymptomatic, or more commonly, their condition is incidentally discovered during neuroimaging. Patients may present with mental retardation or delayed development, seizures, and cerebral palsy.

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A number of syndromes may be associated with ACC. Some of the more common ones include Dandy-Walker syndrome, Aicardi syndrome, fetal alcohol syndrome, and several of the trisomies.  The establishment of a nosologic diagnosis clarifies the etiology of the disease, providing more efficient genetic counseling and treatment options.

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Figs 7.23A and B: Agenesis of corpus callosum (A) CECT head depicting selective dilatation of trigones and occipital horns of lateral ventricles. There was a high riding third ventricle with radial spoke like arrangement of gyri. (B) MRI head- hypoplasia of corpus callosum. This 11-month-old patient was put on to long-term anticonvulsants (Photographs courtesy- Dr Sidharth Kumar Sethi, Dr Anju Aggarwal, Dr MMA Faridi Department of Pediatrics, UCMS and GTB Hospital, Shahdara,Delhi)

LISSENCEPHALY (Fig. 7.24)  Lissencephaly, which literally means “smooth brain,” is a rare brain formation disorder characterized by the lack of normal convolutions (folds) in the brain, and an abnormally small head (microcephaly). It is caused by defective neuronal migration, the process in which nerve cells move from their place of origin to their permanent location.  Symptoms of the disorder may include unusual facial appearance, difficulty swallowing, failure to thrive, and severe psychomotor retardation. Anomalies of the hands, fingers, or toes, muscle spasms, and seizures may also occur. Lissencephaly may be associated with other Fig. 7.24: CECT head-Lissencephaly. There is diseases including isolated lissencephaly smooth thickened cortex with diminished white sequence, Miller-Dieker syndrome, and Walker- matter, there was absent sulci and gyri of the brain. (Photographs courtesy- Dr Sidharth Warburg syndrome. Kumar Sethi, Dr Anju Aggarwal, Dr MMA Faridi  The severe malformations of the brain in Department of Pediatrics, UCMS and GTB lissencephaly most likely will not respond to Hospital, Shahdara, Delhi

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treatment. Normal supportive care may be needed to help with comfort and nursing needs. Seizures may be controlled with medication.  The prognosis for children with lissencephaly is variable depending on the degree of brain malformation. Many individuals show no significant development beyond a 3 to 5 monthold level. Some may have near-normal development and intelligence.

JOUBERT SYNDROME6 (Figs 7.25 A to D)  Joubert syndrome is an autosomal-recessive disorder characterized by cerebellar hypoplasia, hypotonia, developmental delay, abnormal respiratory patterns, and abnormal eye movements.  Careful examination of the face shows a characteristic appearance, and a neuroophthalmologic examination shows the presence of oculomotor apraxia. In the neonatal period, most children have hyperpnea intermixed with central apnea.  Among the associated malformations found in patients ascertained as having Joubert syndrome, 8% of patients had polydactyly, 4% had ocular colobomas, 2% had renal cysts, and 2% had soft-tissue tumors of the tongue.  Neuroimaging of the head in the axial plane demonstrates the “molar tooth sign”—deep posterior interpeduncular fossa, thick and elongated superior cerebellar peduncles, and hypoplastic or aplastic superior cerebellar vermis.

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Figs 7.25A to D: (A) A one-year-old child presented with prolonged pyrexia. He was first issue of nonconsanguinous marriage. He had history of periodic tachypnea and apnea. Note the hypotonia and postaxial polydactyly of fifth toes, occulomotor apraxia and abnormal eye movements. (B) Fundus examination revealed coloboma of disc and choroids. (C, D) CT Scan head revealed vermian agenesis and ‘Molar tooth sign’

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 Differential diagnosis—The “molar tooth sign” could be present in association with the Dandy-Walker malformation and occipital encephalocele. The differential diagnosis of cerebellar hypoplasia consists of conditions related to Joubert syndrome such as Arima syndrome; Senior-Loken syndrome; cerebellar vermian hypoplasia, oligophrenia, congenital ataxia, coloboma, and hepatic fibrosis syndrome; and juvenile nephronophthisis due to NPH1 mutations.

LARGE HEAD (MACROCEPHALY) (Figs 7.26A and B)  The head circumference should be measured during infancy and the maximum occipito frontal diameter is usually 2 cm above the chest circumference in full term neonate. In premature infants the difference is even greater here head appears much large.  The term macrocephaly refers to an occipito frontal diameter of more than 3 SD above the mean. Therefore, committing microcephaly one must plot the exact head circumference on a standard graph.  Hydrocephalus—is one of the most important causes of macrocephaly. Careful clinical examination of fontanels, sutures, skin texture, eye movement and the presenting symptoms are to be done. A cranial ultrasound should be performed in every cases.

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Figs 7.26A and B: Macrocephaly. (A) A neonate with hydrocephalus at birth. (B) A neonate with Hydranencephaly. Please note that clinically all large head appears same unless screened by cranial ultrasound or CT MRI head

 Dandy-Walker syndrome—This condition has a prominent occiput and hydrocephalus. A prominent occiput is also a feature of trisomy 18.  Hydranencephaly—In this condition skull and meanings are normal but the cerebral hemisphere is not developed. The transillumination of head positive.  Porencephaly—Here the patent presents with seizures, infantile spasm, asymmetry of skull and microcephaly, delayed milestone. Transillumination positive over focal area.  Megalocephaly—It may represent the brain growth at upper limit of normal growth seen in familial large head pattern.  Other causes—Cerebral arachnoid cysts, intracranial tumors in infants, thickening of skull like osteopetrosis, osteogenesis imperfacta, and other skeletal dysplasias. Caravans disease, Alexander disease, Russell dwarf, etc.  Transillumination—(Fig. 7.27) It constitutes most important part of physical examination below one year. Procedure requires a flashlight fitted with rubber cuff so that light can be

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 Fig. 7.27: Transillumination test. Note the transillumination over the skull

firmly attached to the skull. Note the transillumination. Translucency beyond 2 to 2.5 cm in the frontal region and over 1 cm in the occipital region may be abnormal. Transillumination is positive in subdural effusion, subdural hematoma, hydrocephalus, hydranencephaly and porencephaly. Suboccipital transillumination is positive in Dandy-Walker malformation.

PHENYTOIN–INDUCED GINGIVAL OVERGROWTH (PIGO) (Fig. 7.28)  PIGO occurs in 10 to 30 percent patient treated by phenytoin. The basic cause of overgrowth being that phenytoin directly stimulates the gingival fibroblast resulting into increased synthesis of collagen.  In severe cases manifestation includes. (1) Gross enlargement of gingiva sometime covering whole of the teeths. (2) Edema and erythema. (3) Secondary infections. (4) Migration of teeth. (5) Inhibition of exfoliation of primary teeth and subsequent impaction of permanent teeth.  Other causes of gingival hyperplasia include use of cyclosporine and calcium chennel blockers. Treatment-Stop the offending drug. Frequent dental checkups. Gingivectomy in severe cases.

Fig. 7.28: Phenytoin-induced gum hyperplasia

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Drug Induced Dystonia (Figs 7.29 A and B)  Acute dystonic reactions can be induced as an idiosyncratic reaction by dopamine depleting drugs such as antihistamines, antipsychotics, antiemetics (domperidone, metoclopramide, prochloperazine) tetrabenazine, and antimalarials. The dystonia usually occurs on the first day of drug exposure and affects the head, neck, and trunk muscles with neck retraction, tongue protrusion, trismus, and oculogyric crisis. Difficulty with swallowing and speaking may occur.

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Figs 7.29A and B: Acute dystonic reaction: (A) Six-year-old patient had spasmodic conjugate deviation of the eye upwards accompanied by synergistic movement of head and neck (Occulogyric crisis). This abnormal posture was caused by drug metachlorpramide, a nonphenothiazine antiemetic that blocks post synaptic dopamine receptors. (B) Two-year-old boy presented with abrupt onset of dystonia of neck with uprolling of eye ball, he has received injection metachlorpramide for vomiting

 Domperidone and metoclopramide use is restricted in children and young adults (under 20 years) in whom acute dystonic reactions are more common, often delayed (tardive) dystonias are seen.  Condition is self-limiting or responds well to anticholinergics (benztropine) or benzodiazepines, but they may be prolonged and resistant to therapy. Tardive Dystonia—The onset is usually 3 to 11 days after treatment with neuroleptics drugs is initiated. The dystonia is usually generalized in children but may be focal in adults. REFERENCES 1. Rajshekharan V, Haran RP, Prakash S. Differentiating solitary small cysticercus granulomas and tuberculomas in patients with epilepsy. J.Neurosurg 1993;78:402-07. 2. Myasthenia gravis; 250 cases in clinical medicine, RR Baliga; 186, third edition 2002. 3. Huppke P et al, Rett syndrome: analysis of MECP2 and clinical characterization of 31 patient; Hum Mol Gen 2000;22:9(9):1369-75. 4. M Ghofrani and T Mahmoodian. Rett syndrome; Indian Journal of Pediatrics 2000;67(7). 5. Angelman syndrome. Consensus for diagnostic criteria. Am J Med Genet 1995;56:237. 6. Chance PF, Cavalier L, Satran D, Pellegrino JE, Koenig M, Dobyns WB. Clinical nosologic and genetic aspects of Joubert and related syndromes. : J Child Neurol. 1999;14(10):660-6; discussion 669-72

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DOWN SYNDROME (Figs 8.1A to C) DEFINITION It is chromosomal disorder, having aberration on chromosome number 21 hence also called as trisomy 21. It was first described in 1866 by John Langdon Down. The condition was labeled ‘mongolism’ due to its facial resemblance to people of mongolian race. CLINICAL FEATURES The facial feature of this condition is so classical that it can be recognized immediately or ‘gestault’ recognition. The patient is hypotonic, short nose with flat nasal bridge, up slanting of palpebral fissure and prominent epicanthic folds, speckling of iris (Brushfield spots), mouth small and tongue appears large. Ears low set with sensorineural deafness in 75 percent patients. Occiput is flat, neck short. CHD is present in 40 percent cases with A-V canal defects. Duodenal atresia is most common gastrointestinal problem associated. Simian crease, short and broad hands with short metacarpals and phalanges, clinodactyly, hypoplasia of middle phalanges of little finger. Wide gap between first and second toe. Hypoplastic pelvis and short stature. Hypothyroidism is more common than hyperthyroidism. Ten fold higher chances of leukemia than general population. GENETIC ASPECTS  Trisomy 21- There are three representatives of chromosome 21 instead of usual two, thus making a total of 47 chromosomes.  Maternal nondysjunction at chromosome 21 is responsible for 95 percent of trisomic cases.  Mosaicism is seen in 3 percent cases.

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Figs 8.1A to C: Down syndrome. (A) note upslanting palpebral fissure, epicanthus folds, prominent tongue, small nose, depressed nasal bridge (B) A 10-year-old girl of Down syndrome, note the Mongolian slant of palpebral fissure, synophrys,epicanthus (C) Cliniodactyly with simian crease

 Translocation is seen in 2 percent cases of which robertsonian translocation is most common. A small number of cases have a isochromosome for the long arm of chromosome 21-t (21q;21q). DIAGNOSIS AND FOLLOWUP       

Gestault recognition of typical phenotypic features. Chromosomal karyotype from peripheral blood. Cardiac assessment to be done in all cases before six months of age. Thyroid screening by TSH and T4 estimation through out childhood. Hearing assessment by auditory brain stem evoked potential between 6 and 8 months. Ocular assessment for cataract, myopia and strabismus at 4 years of age. X-ray cervical spine lateral for atlanto-axial dislocation of spine which is seen in 12 to 20 percent cases.

PRENATAL DIAGNOSIS  Triple test: Screening with triple markers offers a non-invasive method for detection of up to 60 percent of Down syndrome pregnancies. Presence of Down syndrome can be suggested by: • Lower maternal serum alpha fetoprotien (msAFP) levels. • Decreased maternal serum unconjugated estradiol values. • Increased maternal serum human chorionic gonadotropin values. It is performed between 16 and 18 weeks and if positive needs further invasive tests.  Chorionic villous blood sampling by amniocentesis of all mothers above 35 years age.  Antenatal ultrasonography: May reveal increased nuchal fold translucency, duodenal atresia, tracheoesophageal atresia, VSD, ASD, hypoplasia of middle phalange of little finger. This anomaly scan is to be performed at 24 weeks gestation.

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 Fetal nuchal skin thickening: It is increase soft tissue thickening in the posterior aspect of neck. The nuchal thickness of more than 6 mm during second trimesters has a sensitivity of 38 percent and positive predictive value of 69 percent with false positive rate of 0.1 percent for Down syndrome. More recently thickness of more than 3 mm in the first trimester increases the risk of Down syndrome by 10 folds. There are some other condition were increased thickness of skin is seen over nuchal region are:  Chromosomal syndromes: 13q syndrome, xxxx and xxxxy syndromes, trisomy 18, 18p-syndrome.  Nonchromosomal disorders: Multiple pterigium syndrome (Escobar syndrome), KlippelFeil sequence, Zellweger syndrome (cerebrohepatorenal syndrome)

EDWARDS’ SYNDROME (TRISOMY 18) (Figs 8.2A to C) DEFINITION Trisomy of chromosome 18 results in Edwards’ syndrome. It occurs with frequency of 1 in 5,000 live births. This condition is noted in deliveries of aged mothers. Female male ratio is 4:1. CLINICAL FEATURES These babies have low birth weight, prominent occiput, narrow palpebral fissure. Nails are small and finger occupies a peculiar position. Small and second and fifth finger overlap the middle two. Feet have convex profile with prominent heel it is called as Rocker bottom foot it is due to vertical talus. Other anomalies associated are cleft lip, exomphalus, radial aplasia, CHD, horseshoe kidney. 30 percent cases die within 2 month and 90 percent die before one year.

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Figs 8.2A to C: Edwards’ syndrome.(A) Preterm, low birth weight baby with sloping forehead. (B) See the feet profile which is convex and heel prominent ‘Rocker bottom foot’. (C) Characteristic fisting in which second and fifth finger overlaps the middle two

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GENETIC BASIS Most of the cases have regular trisomy. The risk of recurrence is one percent. PRENATAL DIAGNOSIS Second trimester anomaly scan will reveal presence of IUGR, CHD, polyhydramnios, club foot, rocker bottom feet, choroid plexus cyst, large cysterna magna, micrognathia and small nose.

TRISOMY 13 (PATAU SYNDROME) (Figs 8.3A to D) Patau’s syndrome has an incidence of 1in 6000. They have multiple malformations. Craniofacial features include moderate microcephaly with sloping forehead, hypotelorism, small nose and localized scalp defect in parieto-occipital area (Figs 8.3 and 8.4). Scalp defects may be helpful diagnostically as they rarely appear in other abnormalities. They are punched out lesions due to aplasia cutis congenita (Fig. 8.5). The skin is usually totally lacking, but the crater becomes covered with scar tissue postnatally. Postaxial polydactyly is frequent in the hands. Fig. 8.6 shows postaxial polydactyly in both hands. There is flexion of fingers with overlapping and camptodactyly. Fig. 8.7 shows polydactyly of right foot. There is posterior prominence of heel and cleft between first and second toes. Internally, cerebral, renal and cardiac abnormalities are also present frequently.

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Figs 8.3A to D: Patau syndrome (A) Microcephaly with sloping forehead, hypotelorism, small nose. (B) Localized scalp defect in parieto-occipital area. (C) Shows postaxial polydactyly in both hands. There is flexion of fingers with overlapping and camptodactyly. (D) Shows polydactyly of right foot (Photograph courtesy Dr Ramesh Bhatt, Manipal)

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SALDINO-NOONAN SYNDROME (SHORT RIB-POLYDACTYLY TYPE I) (Figs 8.4A to D) CLINICAL FEATURES This condition was originally described by Saldino and Noonan in 19721 Naumoff et al (1977) proposed two distinct type of lethal short rib polydactyly syndrome. Type I and type II. SaldinoNoonan syndrome is comparatively common and characterized by micromelia, postaxial polydactyly, brachydactyly, thoracic narrowing and abnormalities of the cardiovascular system and genitalia.  The base of the ileum is hypoplastic and vertebrae rounded, sometimes with coronal clefts. The ends of the long bones are either pointed or have a convex central area of ossification with lateral metaphyseal spikes. GENETIC ASPECT It is autosomal recessive condition.  It is lethal condition and death occurs within few hours of birth and is due to pulmonary hypoplasia.  Antenatally in the absence of positive family history specific diagnosis is not possible. The condition is suspected in the presence of short limb dysplasia, narrow thorax, and polydactyly. OBSTETRICAL MANAGEMENT The option for termination of the pregnancy must be offered to the patient as soon as the diagnosis has been established.

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Figs 8.4A to D: Saldino-Noonan syndrome. (A) Infant with very narrow thorax, short limbs, and postaxial polydactyly. (B) Severely shortened thorax, short ribs, small pelvis, short tubular bones (C) (D) Note polysyndactyly Ref- Indian Pediatrics 2005; 42:389 with permission

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SHORT RIB POLYDACTYLY SYNDROME TYPE II (MAJEWSKI) (Figs 8.5, 8.6A to C) Majewski described four infants with this lethal form of short-limb dwarfism (1971). CLINICAL FEATURES This is extremely rare condition, presents with short stature with disproportionate short limbs. There is characteristic mid line cleft lip cleft palate. Short flat nose malformed and low set ears. Preaxial and postaxial polysyndactyly of hands or feet. Brachydactyly, short and oval tibia, short rounded metacarpals, narrow thorax, horizontal ribs. Ambiguous genitalia are common. Death is due to pulmonary hypoplasia.

Fig. 8.5: Short rib polydactyly syndrome Type 2. Note large head narrow chest, polydactyly, midline cleft of upper lip

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Figs 8.6A to C: Majewski dysplasia (A) Note midline cleft, depressed nasal bridge, low set ears (B) Polysyndactyly of palms and feet (C) X-ray revels shortening of limb, presence of oval shaped tibia

GENETIC ASPECT It is autosomal recessive condition. Prenatal diagnosis: It has been made in fetuses at risk by identification of short tibia, polydactyly and cleft lip at fetoscopy, or severe micromelia, short ribs with narrow thorax, and polydactyly at ultrasound. The earliest diagnosis has been made at 16th week of gestation.

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OBSTETRICAL MANAGEMENT Termination of the pregnancy must be insisted after the diagnosis of the condition.

THANATOPHORIC DYSPLASIA (Figs 8.7A to C) DEFINITION l

Thanatophoric dwarfism is probably the most common amongst the potential lethal conditions, which presents with disproportionate shortening of the limbs in the newborn. The designation, derived from the Greek ‘thanatophoras’, or ‘death bearing’ was used in the original case description by Maroteaus, Lamy and Robert.5 TD is divided into two clinically defined subtypes. TD type 1 (TD1), the most common subtype, features curved long bones (shaped like a telephone receiver) with the femurs being most affected and a normal skull. TD type 2 (TD2) has a cloverleaf skull associated with straight femur. There is some clinical overlap between these two subtypes. The incidence being one in 20,000.

CLINICAL FEATURES  The patient is delivered with short limb, prominent forehead and depressed nasal bridge. Chest is narrow. Affected individual are usually stillborn or die due to respiratory insufficiency in the neonatal period.

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Figs 8.7A to C: Thanatophoric dysplasia. (A) Note very short bowed limbs, narrow chest with large head, prominent forehead, depressed nasal bridge, mid facial hypoplasia. (B) X-ray Pelvis with lower limb- Shortened long bones with metaphyseal widening and cupping and characteristically curved femur “Telephone receiver”. The iliac wings are hypoplastic, narrow sacrosciatic notches, severe flattening of vertebral body gives ‘H’ or ‘U’ shape in AP radiographs. (C) X-ray chest and abdomen revealed narrow thorax along with classical skeletal abnormalities

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 The vertebral bodies have an H-shaped appearance in frontal radiograph due to flattening of their mid-portions and relative prominence of their pedicles. Pelvis is broad, with horizontal acetabulae. The tubular bones are broad and short. The femora are bowed with a ‘telephone receiver’ configuration, which is pathognomic of thanatophoric dwarfism. GENETIC ASPECTS  Most cases are sporadic. A lethal dominant gene probably causes the condition. Mutation of the Fibroblast Growth Factor 3 (FGFR3) gene has been demonstrated.  Thantophoric dysplasia (TD) associated with clover- leaf skull is a separate condition from isolated TD also called as ‘Kleeblattschadel’ syndrome. The long bones are longer and may not be bowed. The skull changes are very unusual in that the basal and occipital bones are underdeveloped so that parietal bones form most of the back of the skull.6 ANTENATAL DIAGNOSIS A specific diagnosis of this condition is only possible when severe micromelia is associated with cloverleaf skull. In the absence of cloverleaf skull the disease should be suspected when severe rhizomelic dwarfism and a narrow thorax are detected. In 71 percent cases achondroplasia is associated with polyhydramnios. These features may not be evident till late mid trimester. The relationship between femur and BPD become abnormal after 21st and 27th weeks. OBSTETRICAL MANAGEMENT When the diagnosis is certain the option to terminate the pregnancy may be offered to patient since the condition is uniformly fatal.

ACHONDROGENESIS (Figs 8.8A to D) DEFINITION Achondrogenesis is a group of severe disorders that affect cartilage and bone development. These conditions are characterized by a small body, short limbs, and other skeletal abnormalities. As a result infants with achondrogenesis are usually born prematurely, are stillborn, or die shortly after birth from respiratory failure. Some infants, however, have lived for a while with intensive medical support. SYNONYMS Type IA is the Houston-Harris type, Type IB is the Parenti-Fraccaro type, Type II is the Langer-Saldino type and is also called Chondrogenesis Imperfecta. It is difficult to distinguish them clinically. INCIDENCE Rare with probably less than 100 cases reported.

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Mutations in the COL2A1 and SLC26A2 genes cause achondrogenesis. Type I may be inherited as autosomal recessive in some cases. Most of the type 2 are sporadic and are likely to represent new autosomal dominant mutation.

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Figs 8.8A to D: Achondrogenesis: (A and B) A stillborn infant with rhizomelic shortening of limbs, head appears relatively large, short neck, short thorax, (C and D) X-ray whole body reveals very short long bones with metaphyseal widening, vertebral bodies poorly mineralized. Photographs courtesy Dr Nalini Madharia, Raipur, CG.

DIAGNOSIS  Type I achondrogenesis is a severe chondrodystrophy characterized radiographically by poor ossification of the spine and pelvis bones which results in stillbirth or early death.  Type II also presents with the same findings but the mineralization deficit is less severe and the long bones less short. Differential Diagnosis Osteogenesis Imperfecta (type II and occasionally IIIc) and hypophosphatasia also present with demineralization but the limb shortening is not usually as severe. Prognosis Lethal MANAGEMENT Termination of pregnancy can be offered before viability. Standard prenatal care is not altered when continuation the pregnancy is opted for. Confirmation of diagnosis after birth is important for genetic counseling.

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ASPHYXIATING THORACIC DYSPLASIA (ATD) (Figs 8.9A and B) SYNONYMS Jeune syndrome, Jeune thoracic dystrophy syndrome, infantile thoracic dystrophy. ETIOLOGY Autosomal recessive inheritance. Minor manifestations of the disease have been noted in parents of affected children, and therefore, the possibility of heterozygous expression has been suggested. CLINICAL FEATURES Jeune syndrome or asphyxiating thoracic dystrophy (ATD) is a rare autosomal recessive skeletal dysplasia characterized by a small thorax, predominantly rhizomelic brachymelia, renal and hepatic anomalies. Half of the cases have polydactyly. Radiological confirmation of diagnosis is essential. The ribs are short, and the ilia of the pelvis are small, horizontal acetabular roof medial bony projection is visible to give a trident appearance. Premature ossification of capital femoral epiphysis is seen. Newborn with thoracic dysplasia associated with lung dysplasia usually die during the neonatal period due to respiratory failure. In those who survive, chronic renal failure is a common cause of death. Renal histopathology reveals cystic changes later peri-glomerular fibrosis. Cirrhosis liver is also one of the causes of early morbidity. ANTENATAL DIAGNOSIS At present there is no biochemical or genetic marker, which could be used for prenatal diagnosis of ATD. However, prenatal ultrasonography measurements like TC/AC (Thoracic circumference / Abdominal circumference) and RCP (Rib Cage Perimeter)/TC helps in diagnosing skeletal dysplasia associated with small thorax. PROGNOSIS Eighty percent of affected infants die in the neonatal period from respiratory failure and infections. Long- term survivors have been reported but they seem to have milder form of disease.

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Figs 8.9A and B: Asphyxiating thoracic dystrophy. (A) Note small and elongated thoracic cage, protuberant abdomen. (B) Note short horizontal ribs with irregular costochondral junction and narrow thoracic cage

OBSTERTICAL MANAGEMENT Termination of pregnancy is offered when the diagnosis is made in second trimester. There is paucity of data on which to be based the management of cases diagnosed in the third trimester.

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ACHONDROPLASIA (Figs 8.10A to C and 8.11A to G) Achondroplasia is by far the commonest and best-known form of short-limbed dwarfism. CLINICAL FEATURES The characteristic facies, habitus and stance of the achondroplast are unmistakable. They can be diagnosed at birth.  The limbs are disproportionately short (rhizomelic shortening) and the knees are often bowed while lumber spine is lordotic. There is inability to approximate the third and fourth finger produces a ‘trident’ configuration of hand. The forehead is bossed and nasal bridge is depressed.  The general health is good, and the life span is not reduced. Skeletal problems may include premature osteoarthritis, particularly of knee joint. Backache may be troublesome and some degree of spinal cord compression may supervene. Restriction of nasal airway predisposes to upper respiratory infection. Mentality is normal, but intellectuality is compromised in minority of achondroplasts, probably due to mild internal hydrocephalus. Severe hydrocephalus needs sometime shunt surgery.  Radiologically the pelvis is abnormal with small iliac wings have ‘tombstone’ configuration, horizontal acetabular roof with bony spike. The long bones are short and the metaphysis slope. There is translucent area at the proximal ends of the femur in the neonatal period; later narrowing of the interpedicular distances in the lumber region becomes evident. Skull is relatively large, with frontal prominence and a small foramen magnum.

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Figs 8.10A to C: Achondroplasia. (A) Short stature with rhizomelic shortening of limbs, with broad prominent forehead. (B) X-ray upper limb. Note rhizomelic shortening (C) X-ray pelvis and legs Note short round ilea crest, horizontal acetabular roof

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GENETIC ASPECTS Achondroplasia is an excellent example of autosomal dominant inheritance the gene is invariably penetrant, with persistent clinical expression. More than 80 percent of achondroplasts have normal parents.8 These ‘sporadic’ patients are assured to be the result of new mutation of particular gene, which has taken place before conception. Murdoch et al2 have shown that there is a significant increase in the average age of the unaffected fathers of sporadic achondroplasts. Achondroplasia, therefore, ranks as one of the disorders in which paternal are effect in the genesis of a new mutation has been demonstrated. The gene maps to 4q and mutation have been demonstrated in the fibroblast growth factor receptor3 (FGFR3) gene.

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Figs 8.11A to G: Achondroplasia. (A) (B) Note large and prominent forehead, rhizomelic shortening and lumbar lordosis (C) Chest X-ray-small thorax, shortened and anteriorly splayed ribs (D) X-ray pelvis- elephant earshaped iliac wings. narrow sacrosciatic notches, flat acetabular roofs (E) X-ray skull - enlarge with significant midfacial hypoplasia, hydrocephalus rarely presents, small skull base with tight foramen magnum (F) X-ray spine shows short pedicle of vertebral bodies with decreased interpedicular distance most marked in the lumbar spine. Posterior vertebral scalloping which persists through the life (G) Normal parent of an achondroplast child, explains fresh mutation, here the recurrence risk are small

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COUNSELING Unaffected parents of achondroplasts can be reassured that the risk of recurrence in further offspring is very low. If an achondroplast married to normal individual, the offspring will definitely be an achondroplastic. If both parents are achondroplasts then there is theoretical chance of 25 percent of infants may be homozygous for abnormal gene, 25 percent may be homozygous for normal gene and rest 50 percent may be heterozygous for abnormal gene. PRENATAL DIAGNOSIS Prenatal diagnosis of achondroplasia has been reported by several authors.9 The diagnosis has been relied on identification of shortened long bones, particularly the femur. But it has been noted that the shortening has not been picked up until the third trimester, and therefore a diagnosis before viability may only be possible in the most severe cases. PROGNOSIS This condition is compatible with normal life. Recurrent ear infection occurs due to poor development of facial bones and inadequate Eustachian tube drainage. Crowded dentition may lead to malocclusion. Average height in men 52 inches and in female 49 inches. Hydrocephalus and syringomyelia may be because of small foramen magnum. Sudden death and respiratory compromises is attributed to compression of upper cervical spine. The most significant handicaps in these patients are neurological complications secondary to spinal cord compression; which may range from paresthesias to complete paraplegia.

TURNER’S SYNDROME (Figs 8.12A to C) DEFINITION It is a syndrome characterized by short stature female, sexual infantilism, streak gonads, absence of second sex chromosome and other somatic anomalies. SYNONYM Gonadal dysgenesis, XO syndrome, Ulrich-Turner syndrome. GENETICS Most cases (50%) have XO karyotype in every cell. About 15 percent cases have mosaic pattern 45X, / 46XX and 45X/47XXX. INCIDENCE Between 1 in 2,500 and 1 in 6000. About 98 percent of pregnancies involving Turner syndrome abort spontaneously.

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Figs 8.12A to C: Turner syndrome. (A) Newborn with webbing of neck, low posterior hairline, edema of hand (B) Pedal edema (C) Webbing of skin and low posterior hair line

CLINICAL FEATURES Short stature (adult height usually < 144 cm), broad chest with wide spaced nipple, webbing of posterior neck (about 50% cases), lower posterior hair line, short neck, hyperconvex nails and cubitus valgus (increased carrying angle of arms), lymphedema of dorsa of hands and feet. OTHER FEATURES CHD (15-30% cases) Bicuspid aortic valve (50%), coarctation of aorta (20%), aortic root dilatation (10%), aortic stenosis, anomalous pulmonary venous return. Renal anomalies like horseshoe anomalies, UPJ obstruction, absence of kidney. Hearing loss. Abnormally large ears, epicanthus, ptosis of upper eyelid, downward and outward slant of palpebral fissure, short fourth metacarpals, cutaneous nevi, which increase with age. Lack of sexual maturation with primary amenorrhea in a teenager. Intelligence is normal with some impairment in cognitive function like visual-spatial processing, visual memory. Associated diseases are primary hypothyroidism, diabetes mellitus, ulcerative colitis, Crohn’s disease. LABORATORY INVESTIGATIONS  Karyotyping in every suspected cases.  Buccal smear for sex chromatin (Barr body).

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 Hormonal assay (FSH, LH, TSH, T4).  Bone age.  USG – reveals small ovaries with often streak like appearance, horseshoe kidney and other related anomalies.  Echo evaluation of heart to pick up cardiac anomalies and to monitor progressive dilatation of aortic root. TREATMENT  To enhance the height of patient growth hormone therapy usually between 2 and 5 years. It has to be continued until growth velocity decreases to less than 2.5 cm/year with a bone age over 15 years.  It is quite expensive as dose required is very high. Cyclical estrogen progesterone treatment at pubertal age will induce withdrawal bleeding and give psychological satisfaction to patient. Manage other associated anomalies accordingly.

NOONAN’S SYNDROME (Fig. 8.13) INCIDENCE Unclear may be as high as 1 in 1,000. ETIOLOGY Sporadic although some AR and AD familial cases are reported. A gene has been mapped to 12q11-qter. PERFORMANCE Mild MR in 50 percent cases. KEY FEATURES Short stature (more than 66% of cases), broad forehead with ptosis, malformed ears, (low set, fleshy fold sod upper transverse helix), low posterior hairline with webbed neck. OTHER FEATURES CHD is seen in more than 50 percent of cases. Common CHD are seen valvular pulmonary stenosis, peripheral pulmonary artery stenosis, PDA, ASD VSD, aortic coarctation and Ebstein anomaly. Cryptorchidism, epicanthic folds, hypertelorism, micrognathia, flat nasal bridge, (saddle nose). One third cases shows variety of bleeding disorders. Noonan’s syndrome should not be referred to be as “Male Turner’s syndrome”.

Fig. 8.13: Noonan’s syndrome. Sixyear-old patient with short stature, characteristic facies, pectus excavatum, and wide spaced nipple. This patient had systolic murmur at pulmonary area, confirmed to have pulmonary stenosis on echocardiography

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DIFFERENTIAL DIAGNOSIS Noonan’s syndrome has to be differentiate from XO/XY mosaicism, fetal hydantoin syndrome, fetal myosoline syndrome and fetal alcohol syndrome.

MARFAN’S SYNDROME (Figs 8.14A and B) INCIDENCE Between 1 in 16,000 and 1 in 60,000. ETIOLOGY Autosomal dominant inheritance (Fibrillin (FBN1) mutation in chromosome number 15q21). KEY FEATURES Skeletal Tall stature, long cylindrical limbs (arm span longer than the height), distance from pubis symphysis to heel is greater than distance to crown. The skeletal abnormalities present are Arachnodactyly, pes planus, joint laxity with scoliosis in 60 percent kyphosis. Pectus excavatum or carinatum. Flexing thumb in the fist, the thumb crosses the ulnar border of palm is called as “Thumb Sign” (Steinberg’s sign). Eyes Sublaxation of lens usually upward with defect in suspensory ligament. Myopia and retinal detachment.

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Figs 8.14A and B: Marfan’s syndrome: (A) Note tall thin habitus with arachnodactyly. (B) Steinberg’s sign

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Dilatation of aortic root, with or without dissecting aneurysm of ascending aorta. Mitral valve prolapse and regurgitation. Other Features Joint hyperextensibility, scoliosis, kyphosis, narrow face, myopia, retinal detachment, glaucoma, hernias, large ears, sleep apnea. FOLLOW-UP MANAGEMENT  Prevention of scoliosis is important during childhood.  To start beta-adrenergic blocking drug as soon as diagnosis of Marfan’s syndrome is made. It reduces the incidence of aortic dissection and dilatation.10  Secondary glaucoma has to diagnosed and managed accordingly.

ROBIN ANOMALAD (Fig. 8.15) SYNONYM Cleft palate, microphthalmia and glossoptosis and Pierre Robin syndrome. DEFINITION This is characterized by the association of micrognathia and glossoptosis. Frequently a posterior cleft palate or a high arched palate. Incidence The frequency is 1:30,000. Etiology Sporadic in 40 percent cases. Autosomal dominant and recessive nature has also been noted. Embryology The primary disorder is probably an early hypoplasia of the mandible. This would lead to posterior displacement of tongue thus preventing the normal closure of posterior palatine process.

Fig. 8.15: Micrognathia in Pierre Robin sequence (Photograph courtesy Dr Ramesh Bhatt, Manipal)

Pathology Hypoplasia of mandible causes foreshortening of floor of mouth and reduction of size of the oral cavity. As a result there is tendency to glossoptosis, which may alter the development of the palate and lead to a posterior cleft or a high arched palate.

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Associated Anomalies Forty percent cases are seen as isolated robin anomalad. In 36 percent one or more anomalies are associated. In 25 percent cases it is associated with known syndrome.

ALBINISM (Figs 8.16A and B) DEFINITION It is an autosomal recessive disorder characterized by pigmentary disorder having normal number of melanocytes but absent or defective tyrosinase activity resulting in diminished or absent melanin production.

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Figs 8.16A to B: Albinism (A) Tyrosinase negative albinism which is characterized by white hairs (B) Tyrosinase positive albinism, which is more common type, characterized by reddish blonde hairs

 Albinism can be separated into those individuals with only eye involvement (Ocular albinism) and those with eye, skin and hair abnormality (Oculocutaneous albinism OCA). There are four classes of OCA, with multiple subsets in each class.  The gene locus is in chromosome 15q for tyrosinase – positive albinism (TPA) and in chromosome 11q for tyrosinase negative albinism (TNA).  Hair bulb incubation test: It is a laboratory method for identifying TPA and TNA types of albinism. Incubation of hair bulb in L- tyrosine 1mg/ml in 0.1 M phosphate buffer at pH 6.8. In TPA, melanin production is detected in the hair bulb, in TNA no melanin production is detected.  Classification of OCA• Tyrosinase related OCA1 • No tyrosinase activity OCA1A • Residual tyrosinase activity • Yellow OCA 1B • Minimal pigment OCA1MP • Unusual tyrosinase activity • Temperature sensitive OCA1TS • Tyrosinase positive OCA2 • Prader Willi/Angelman syndrome

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Clinically color of skin is pink to cream. Hairs are cream to brown color in TPA and snow-white color in TNA. Ocular manifestations are blue to brown iridae, photophobia, nystagmus, diminished visual acuity, strabismus. Complications—It is in the form of sun burn and skin cancers. Treatment—Avoid sun exposure and adequate application of sunscreen before exposure to sun. Surveillance of skin cancer and genetic counseling.

HURLER’S SYNDROME (Figs 8.17A to C) INCIDENCE 1 in 100,000 live births. ETIOLOGY Autosomal recessive. The primary defect is an absence of lysosomal hydrolase alpha-L iduronidase (IDUA), it is responsible for degradation of the glycosaminoglycans, heparan sulphate and dermatan sulphate. The IDUA gene is mapped to chromosome 4p16.3. PERFORMANCE Marked mental retardation, normal at birth with progression to syndromic features and increasingly severe developmental delay. KEY FEATURES Scaphocephalis macrodactyly, coarse facies, anteverted nostrils, depressed nasal bridge, hypertelorism, corneal clouding, enlarge lips claw hands, hernias (umbilical, inguinal).

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Figs 8.17A to C: Hurlers syndrome. (A) A five-year-old child with coarse facies, macrocephaly, thick lips, limitation of extension of both upper and lower limbs (B) X-ray lumbar spine, short and anterior wedging of thoracolumbar vertebrae. (C) X-ray wrist—note the proximal tapering of the metacarpals, coarse trabaculation and irregular epiphysis

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Other Features Open mouth, nasal discharge, macroglossia, thick gums, abnormal placed teeth, kyphosis, short neck, gibbus, hirsutism, hepatosplenmegaly, pectus carinatum and excavatum, characteristic X-ray finding with coarse trabaculation. DIAGNOSIS It is confirmed by clinical diagnosis and biochemical investigation. The excretion of dermatan sulphate and heparan sulphate in urine, and the absence of alpha- L–iduronidase in fibroblast culture. Antenatal diagnosis is possible by detection of alpha-L-iduronidase level in amniotic fluid cells.

MORQUIO’S SYNDROME (Figs 8.18A and B) SYNONYM Mucopolysaccharidosis type IV. INCIDENCE 1 in 40,000 Types Type A- Severe form of the disease. There is deficiency of enzyme N-acetylgalactosamine6-sulphatase. Type B is mild form of disease. There is deficiency of Beta galactosidase enzyme. ETIOLOGY Autosomal recessive. The type A has been linked to chromosome 16q24.3, type II Morquio’s syndrome is linked to chromosome 3p21.33.

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Figs 8.18A and B: Morquio’s syndrome (A) Seven-year-old patient with short neck, short trunk, pectus carinatum, coarse facies, genu vulgus, kyphosis (B) X-ray spine lateral view note the generalized platyvertebrae

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No mental retardation, normal at birth with progression to syndromic features, shortened life span. KEY FEATURES Mildly coarsened features, (not always present), broad mouth, short neck, with restricted movement, pectus carinatum, short stature, short trunk, marked platyspondyly, with vertebrae changing to ovoid with anterior projection, knocked knees. Other Features Short anteverted nose, cloudy cornea (late in first decade of life), abnormal teeth (pitting and enamel hyperplasia), hepatomegaly, short/stubby hands, joint laxity, scoliosis, lumbar lordosis, tendency to C1-C2 dislocation (with spinal cord compression), progressive hearing loss, aortic regurgitation (later in life). DIAGNOSTIC CONFIRMATION Depends upon two- dimensional electrophoresis or thin-layer chromatography of isolated urinary glycosaminoglycans. False negative test are seen for urinary mucopolysaccharides, therefore the deficiency of enzymes in cultured fibroblasts or leukocyte is more specific for confirmation of diagnosis. Prenatal diagnosis is possible using both amniotic fluid cells and chorionic villi.

PROGERIA (HUTCHINSON GILFORD PROGERIA SYNDROME) (Figs 8.19A to D) INCIDENCE One in 250,000 to 1 in 4,000,000. ETIOLOGY Most cases are sporadic. Although there have been a few reports of affected siblings. PERFORMANCE No MR Life span in most cases ranges from 12 to 13 years and is due to possible complications such as atherosclerosis (myocardial infarction or stroke). KEY FEATURES Alopecia onset between birth and 18 years. Skin is thin dry, warm (early skin is described as scleroderma, i.e. thick and inelastic). Facial hypoplasia, with marked micrognathia, thin nose with sculpted appearing tip, loss of subcutaneous fat (cheeks and pubic area are last to be lost), head appears large for face, open fontanel’s, joints are stiff and partially flexed, growth deceleration 9 between 6 months and 18 months).

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Figs 8.19A to D: Progeria (A) Six-year-old boy with alopecia, deficient growth, facial hypoplasia, micrognathia,stiff and partially flexed prominent joint “Horse riding stance” (B) Skin thin with sclerodermatous changes, nails hypoplastic, brittle curved and yellowish (C) X-ray hip joint coxa vulga (straight femur) (D) X-ray chest—Absent clavicle

OTHER FEATURES Typical early sign (mid facial cyanosis), delayed dentition, high-pitched voice, prominent eyes, thin lip, dystrophic nails (thin, short, and small), and prominent appearing joint. Skin develops brown spots and pigmentation.

GOLDENHAR SYNDROME (Figs 8.20A and B) SYNONYM Facioauriculo-vertebral syndrome, First and second branchial arch syndrome, Hemifacial Microsomia. DEFINITION It is association of non-random defect of the first and second branchial arch, associated with vertebral and ocular anomalies. These abnormalities are asymmetric and 70 percent cases are unilateral involvement. INCIDENCE The frequency of occurrence is estimated to be 1 in 3000 to 1 in 5000, and there is slight (3:2) male predominance.

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B Figs 8.20A and B: Goldenhar syndrome (A) (B) Bilateral limbal dermoid, hemifacial microsomia left half of face, ear abnormalities

CLINICAL ABNORMALITIES Face is affected asymmetrically, with ears small and malformed, pre-auricular skin tags. Cervical and vertebral anomalies are common. Epibulbar dermoid is important diagnostic feature. When this is absent the term first and second branchial arch syndrome is used. When the face is affected on only one side without an Epibulbar dermoid then term used as Hemifacial microsomia. Genetic aspects: Sporadic in most cases. Occasional dominant families are described.

MECKEL GRUBER SYNDROME (Figs 8.21A to C) SYNONYM Dysencephalia splanchnocystica. DEFINATION This syndrome is describes by Meckel in 1822 and later by Gruber. The diagnostic features are occipital encephalocele, post axial polydactyly and polycystic kidneys. ASSOCIATED ABNORMALITIES Includes microcephaly, hydrocephaly and anencephaly, agenesis of optic chiasma, corpus callosum, microphthalmia, ear anomalies and others. GENETIC ASPECTS Autosomal recessive. The locus is been mapped to 17q21-q24. ANTENATAL DIAGNOSIS It is possible to detect MGS Antenatally by elevated alpha-fetoprotein level in the presence of encephalocele. Antenatal ultrasonography demonstrates paracranial mass, polydactyly.

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Figs 8.21A to C: Meckel Gruber syndrome: (A) Huge occipital encephalocele, postaxial polydactyly (B) Cleft lip and palate (C) X-ray revealing huge encephalocele

OBSTETRICAL MANAGEMENT Termination of pregnancy is offered before viability. In third trimester obstetrical management depends on amount of herniated brain, size of the defect and associated anomalies.

CHARGE SYNDROME (Figs 8.22A and B) INCIDENCE Unclear ETIOLOGY Sporadic (possible from insult during second trimester). PERFORMANCE MR is most cases, early feeding problems. KEY FEATURES    

Coloboma (usually retinal coloboma). Heart abnormalities (TOF, PDA, VSD, ASD). Atresia of the choanae. Retardation (MR and postnatal growth retardation).

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Figs 8.22A and B: Charge syndrome (A) Coloboma of iris at 5 and 7 O’ clock position (B) Vertical scar mark of operated VSD, with absence of left depressor angularis oris muscle

 Genital hypoplasia (in male, microphallus and cryptoorchidism).  Ear abnormalities (small ears, cup-shaped lop ears, deafness). Other Features Microcephaly, facial asymmetry, facial palsy, malar flattening, long philtrum, cleft lip palate, small mouth, swallowing difficulties, and polyhydramnios.

APERT’S SYNDROME (Figs 8.23A to C) SYNONYM Acrocephalosyndactyly. ETIOLOGY Autosomal dominat. Most of the cases are sporadic and are associated with old paternal age. It is caused by mutation in the fibroblast growth factor receptor 2 gene (FGFR2) which maps to chromosome number 10a25-10q26. The recurrence risk for the unaffected parents of a child with Aperts is negligible, whereas the recurrence risks for the affected individual is 50 percent. KEY FEATURES At birth all the cranial sutures are abnormal, apart from lamdoidal, and the head is tower shaped, flat from front to back with a prominent forehead. Eyes are prominent, the nose beaked and high arched palate. The hands are characteristic with fusion of digits two to five and sometime including thumb. Fusion of cervical vertebrae C5-C6 is seen in 70 percent cases. 50 percent cases shows mental retardation. There is associated polymicrogyria, hypoplastic white matter, and hetrotropic grey matter.

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Figs 8.23A to C: Apert’s syndrome (A) Unusual head shape, brachycephaly, acrocephaly, proptosis, beaked nose (B) (C) Syndactyly of finger and toes

FUTURE MANAGEMENT  Surgery is indicated for craniosynostosis when there is indication of raised intracranial pressure.  Early surgery to release the thumb to allow pincer grasp is recommended.  Hearing assessment to be done to detect hearing loss.  Facial and cosmetic reconstruction by plastic surgeon.

DISORGANIZATION-LIKE SYNDROME (Fig. 8.24) Disorganization-like syndrome is a rare occurrence of multiple congenital anomalies, the spectrum of which ranges in different studies. The occurrence of these anomalies is difficult to explain by amniotic bands. It was suggested that these might results from a mutant gene, the homologue of mouse mutant “disorganization” (Ds). There is high frequency of limb duplication (usually involving a single limb), polydactyly, and limb originating from abnormal sites.

Fig. 8.24: Disorganization-like syndrome. 11 Note lumbosacral masswith duplication of foot. Ref-Indian Pediatrics 2003; 40:268 , with permission.

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KABUKI MAKE-UP SYNDROME (Figs 8.25A to D)  It is characterized by peculiar face, which mimics the make-up of Kabuki, the traditional Japanese theatre.  It is consists of mental retardation, short stature, long palpebral fissure, outer one third everted lower eye lids, ptosis, arching of eye brows, epicanthus, short nasal septum, protuberant ears, cleft palate tooth abnormality, open mouth with tented upper lip giving myopathic look.  Incurved fifth little finger due to shortening of fourth and fifth metacarpals, they have prominent fetal pads (prominent fingertip pads) brachydactyly, hip dislocation, sagittal cleft of vertebral bodies.  Cardiac defects include coarctation of aorta, bicuspid aortic valve, mitral valve prolapse, membranous VSD, pulmonary, aortic and mitral valve stenosis. Cardiac defects are observed in about 50 percent of cases. These cases are said to have sporadic mutation.

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Figs 8.25A to D: Kabuki make-up syndrome. (A) 4 years old female patient with characteristic facial feature like tenting eyebrows, everted outer one third lower eyelids, long palpebral fissure (B) open mouth with tented upper lip. (C) Note the prominent fingertips (fetal pads). (D) Plain X-ray of hip joint displaying dislocated right femoral head with pseudoarthrosis

LESCH-NYHAN SYNDROME (Figs 8.26A to D)  This syndrome presents with hyperuresemia, choreoathetosis and self-mutilating behavior.  It is an X-linked recessive disorder with gene location at (Xp26-q27.2). There is deficiency of Hypoxanthine guanine polyribitol transferase (HGPRT).  Onset is within first few months with developmental retardation, and the full clinical picture develops before 2 years. The psychomotor retardation is seen by first year. The extra pyramidal movements are seen by age 8-24 months. The involuntary self-destructive behavior in the form of biting of the arms, lips are apparent by 4 years.  Few patients have association of anal atresia, Hirschsprung’s disease and cryptorchidism.  The investigations consists of elevated serum uric acid, increase in urinary uric acid, the ratio of urinary uric acid to creatinine ratio of > 3:1 is diagnostic.

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TREATMENT Allopurinol is used to reduce the hyperuricemia and thus, renal damage is prevented. For selfinjurious behavior resperidone is tried, to allay the anxiety diazepam has been tried, and carbamazepine or gabapantene as mood stabilizers.

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Figs 8.26A to D: Lesch-Nyhan syndrome (A) (B) Picture depicts the extent of facial injury caused by self-injurious behaior (C) (D) Depicts the choroathetoid movement exhibited by patient

POLAND SEQUENCE (Figs 8.27A to C)  The main features in this syndrome are the presence of following unilateral features. • Hypoplasia to absence of pectoralis major muscle, nipple and areola • Hypoplasia of upper limb with varying degree of syndactyly, brachydactyly, oligodactyly. • Occasionally hemivertebrae, renal anomalies and dextrocardia in left sided Poland sequence.  Bavinck and Weaver suggested that Poland, Klippel-Feil and Mobius sequences all of which may occurs in common in same individual, and all should be grouped in the category of subclavian artery disruption syndrome. It is said that it is due to diminished blood flow in the subclavian artery, vertebral artery, and their branches during or around the sixth week of development.12

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Figs 8.27A to C: Poland sequence (A) (B) Left Poland sequence (C) X-ray showing Hypoplastic left limb with digital defects

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OSTEOPETROSIS (ALBERS-SCHÖNBERG SYNDROME) (Figs 8.28A and B)

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Figs 8.28A and B: Osteopetrosis (A) Photograph showing failure to thrive, macrocephaly, hepatospleenomegaly (B) X-ray depicting ‘Bone within bone appearance’

 This is one of the important bone dysplasia displaying increased bone density. There are two types of osteopetrosis. • Autosomal recessive (OMIM 259700)13 • Autosomal dominant (OMIM 166600)  Most of the clinical features due to failure to remodel growing bones. This leads to narrowing of cranial nerve foramina and encroachment of marrow space, which results in secondary complications such as optic nerve dysfunction, anemia.  From birth the bones are sclerotic with poor modeling giving appearance of ‘bone within bone appearance’. There is microcephaly, square shaped head, frontal bossing, ptosis and strabismus.  Treatment: Bone marrow transplantation is successful in some patient. Calcitrol and interferon gamma has been used with some benefit. Rest all symptomatic treatment.

POTTER SYNDROME (Figs 8.29A and B)  The term Potter syndrome is given to a lethal condition due to bilateral renal agenesis and death occurs due to pulmonary hypoplasia.  The characteristic facies called as ‘Potter facies’ and consists of widely placed eyes, epicanthus, low set ears, nose broad and compressed, receding chin and limb abnormalities.  This condition is picked up in pregnancy when there is severe oligohydramnios, nonvisualization of kidneys and bladder. The incidence is 1 in 3,000 birth and represents 20 percent of newborn with potter phenotype. Other causes of neonatal renal failure with Potter phenotype represents cystic renal dysplasia, obstructive uropathy, autosomal polycystic kidney disease, renal hypoplasia.

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FIBULAR HEMIMELIA (Figs 8.30A to C)  Deformities of the fibula ranges from mild deficiency of the proximal end of the bone to complete absence accompanied by multiple malformation of the neighboring structure.  Unilateral deformity is more common than bilateral one. It is associated with short bowed tibia, absence of lateral rays of foot.

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Figs 8.30A to C: Fibular hemimelia. 14 (A) Fibular hemimelia of right limb, note the absent lateral rays, and a

cutaneous dimple corresponds to pseudoarthrosis of tibia (B) Fibular hemimelia of right foot in a newborn. (C) Xray depicting pseudoarthrosis of tibia and absent fibula. R ef- Indian Pediatrics 2003; 40:359, with permission.

PROBOSCIS LATERALIS (Fig 8.31)  Proboscis lateralis is a rare facial anomaly (1:100,000 birth) resulting in incomplete formation of nose, the eye and adenexa. It consists of a soft, trunk like process that originates from the medial portion of the orbit roof.

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 It is often associated with other malformations of facial region including abnormality of eye and lacrymal system and facial bone formation.  It is hypothesized that each nostril develops separately and fuses at a later stage to form the nose. This can explain anomaly seen in this condition. Antenatal diagnosis of this condition is possible by detection of finger like projection in area of the eye.

Fig. 8.31: Proboscis Lateralis 15 and complete absence of left nostril

BARDET-BIEDL SYNDROME (Figs 8.32A to C)  The manifestation of this syndrome was first described by Laurence and Moon in 1865, it was referred to Laurence-Moon-Biedl syndrome, but after 1920 more than 300 cases have been reported by Bardet-Biedl, hence called now as Bardet-Biedl Syndrome.1  It consists of polydactyly, retinal dystrophy, mental handicap, obesity and hypogonadism.  Polydactyly is postaxial. Although syndactyly, brachydactyly of hands and broad and short feet are also present.  Ocular manifestations are in the form of retinal dystrophy in 100 percent cases followed by myopia, nystagmus, glaucoma, posterior capsular cataract, retinitis pigmentosa.16  Mental retardation might not be always there.  The frequency of other abnormalities are obesity 90 percent, diabetes mellitus 50 percent, hypogonadism in male 88 percent, menstrual problems in female 100 percent, renal problems are seen in 90 percent cases in the form of calyceal clubbing, cyst or diverticulae, fetal lobulations, renal cortical loss, renal failure.17  Genetic aspect—It is autosomal recessive but mark variability in expression. Gene linked to 16q13-q22, 11q13 were found in different studies.

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Figs 8.32A to C: Bardet-Biedl syndrome (A) Note the obesity polydactyly and hypogonadism (B) Postaxial polydactyly and syndactyly (C) Hypogonadism

VATER SYNDROME (Figs 8.33A and B)  The acronym VATERS stands for non-random association of vertebral defects and VSD, imperforate anus, esophageal atresia with T-E fistula, radial and renal dysplasia, and single umbilical artery.  Other less frequent defect associated are prenatal growth deficiency, postnatal growth deficiency, laryngeal stenosis, ear anomaly, defects of lower limb, etc.

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Figs 8.33A and B: Vater syndrome (A) Neonate with VATER anomalies (B) X-ray showing vertebral defect, imperforate anus

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 Most of these patients have normal brain function, hence, merit vigorous attempts towards rehabilitation, surgical and otherwise.  Etiology: Idiopathic mostly, sporadic instances seen in family. More frequently seen in offsprings of diabetic mothers. Clinician should note that similar anomalies with more broader pattern are seen in trisomy 18 or del (13q) syndromes, Holt-Oram syndrome and VATER with hydrocephalus, the prognosis in such cases are guarded. One must rule out their presence before framing the prognosis.

BLEPHAROPHIMOSIS SYNDROME (Fig. 8.34)  This disease coined its name in the year 1889 by Vignes as a dysplasia of eyelids. There are two types: Type I—associated with infertility in female and complete penetrance of the altered gene. Type II— transmitted by both male and female and associated with incomplete penetrance.  There is reduced horizontal diameter of palpebral fissure, droppy eyelids, a fold of skin, which runs from lower lid medially and upwards. Flat nasal bridge, ears may be normal or cup shaped, with normal intelligence. Fig. 8.34: Note blepharophimosis, ptosis Early milestone appears to be achieved slightly late and epicanthus inversus because of backward head tilt due to ptosis and blepharophimosis.  There is increase tendency of menstrual irregularities and infertility in female. Autosomal dominant with gene location to 3q23.

MILROY-HERIDITARY LYMPHEDEMA (Fig. 8.35)  Milroy’s disease is congenital form of lymphedema, which is usually confined to lower limbs. The swelling is firm but it does pit on pressure.  The cause of lymphedema is aplasia and hypoplasia of lymphatics.  The condition is autosomal dominant.

Fig. 8.35: Milroy’s disease. 3 months old infant with bilateral lower limb edema with hypertrophy of penile skin (Photographs coutesy: Dr Alok Purohit and Dr Sagori Mukhopadhyay (SMS) Hospital Jaipur)

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MACRODYSTROPHIA LIPOMATOSA (Figs 8.36A and B)  Macrodystrophia lipomatosa is a congenital form of macrodactyly seen at birth. It is progressive condition characterized by an increase in mesenchyme elements, especially the fibro adipose tissue. The abnormality is always unilateral, and usually in the distribution of the median nerve (upper extremity) and the plantar nerve (Lower extremity).

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 Radiographic examination demonstrates macrodactyly including the soft tissue and the bone. The trabeculae are normal. T1–weighted coronal MRI image shows marked proliferation of adipose tissue. A high signal linear structure with low signal rim along the involved areas may correspond to a thickened nerve.  Macrodystrophia lipomatosa should be differentiated from other causes of congenital macrodactyly, hemangioma, Klippel-Trenaunay-Weber syndrome, Ollier’s disease and Proteus syndrome.

MAYER-ROKITANSKY-KUSTER-HAUSER SYNDROME19–22 (Figs 8.37A to D) The MRKH is comprised of vaginal atresia with other Müllerian (i.e., paramesonephric) duct abnormalities, skeletal abnormalities and renal abnormalities. MRKH is characterized by Müllerian duct structures agenesis, in genetically, phenotypically and developmentally normal (46XX) females. It usually remains undetected until the patient presents with primary amenorrhea despite normal external development. The MRKH is the most common congenital cause of primary amenorrhea. Although this condition has psychologically devastating consequences, its physiological defects can be treated surgically. Following diagnosis, surgical intervention allows patients to have normal sexual function. Reproduction may be possible with assisted techniques. Incidence statistics vary from 1: 4000 (at birth) to 1:20,000 at female hospital admissions. EMBRYOLOGY Around the fifth gestational week, the müllerian ducts stop developing. The skeleton, derived from the embryonic mesoderm, is vulnerable to developmental disturbances at this time. The

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Figs 8.37A to D: MRKH syndrome: (A) Apparently a pair of ill developed labia majora like structure seen on standing posture with a protruding mass similar to hypertrophied clitoris was found overhanging the external genitalia. (B) Congenital absence of thumb. (C) Congenital kyphoscoliosis and absence of widening of pelvis in the late adolescence. (D) External urethral meatus covered by a structure resembling labio-scrotal folds containing adequate amounts of rugae with a raphe mimicking the texture of scrotal skin, fused at upper end with a whirling pattern resembling clitoris. Photographs by Dr Ranbir Pal and Dr Ankur Barua, Sikkim Manipal Institute of Medical Sciences

uterus, cervix, and upper 75 percent of the vagina form from the fused caudal ends of the Müllerian ducts. Fallopian tubes develop from the unfused upper ends; the renal system simultaneously develops from the wolffian ducts. Ovarian function is preserved because the ovaries originate within the primitive ectoderm, independent of the mesonephros. A gene responsible for MRKH has not been identified. COMPONENTS 1. Absence of vagina and rudimentary cornua uteri but morphologically normal ovaries and fallopian tubes. External features and ovulation are normal but the woman is amenorrheic and infertile. 2. Urinary tract anomalies, most common being renal agenesis, ectopia and fusion, occurs in about one-third cases. 3. Skeletal abnormalities are seen in 12 percent cases, 2/3rd of them being abnormalities of spine, limb and rib. A term MURCS association has been coined to denote Müllerian duct aplasia, renal aplasia and cervicothoracic somite association (Klippel-Feil type). Other abnormalities such as congenital heart conditions and inguinal hernia may also be associated.

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PRESENTATION Primary amenorrhea and cyclic abdominal pain are common. The patient undergoes puberty with normal thelarche and adrenarche; however, menses do not begin. Because ovarian function is normal, patients experience all bodily changes associated with menstruation. On examination, height is normal. The vulva, labia majora, labia minora, and clitoris are normal. Speculum examination of the vagina may be impossible or difficult because of the degree of vaginal agenesis. Infertility Patients who do not undergo evaluation for primary amenorrhea often seek clinical attention for infertility. Inability to have intercourse. The more shallow the vaginal canal, the greater the likelihood of the patient having dyspareunia. Some patients present with a history of voiding difficulties or recurrent urinary tract infections. WORK-UP 1. Lab studies: Chromosomal analysis is essential to exclude karyotypic abnormalities of the X chromosome (e.g., Turner’s syndrome). Other chromosomal aberrations may include a 46, XY karyotype, suggesting a form of androgen insensitivity syndrome. Normal circulating levels of human chorionic gonadotropin (HCG), luteinizing hormone (LH), and follicle stimulating hormone (FSH) indicate appropriate ovarian function. 2. Imaging studies • Sonography: Sonography easily depicts the upper level of the vagina and the length of its obstruction. It can identify uterine duplications and tubal obstruction. It can rule out a hydrocolpos or a hydrometrocolpos. It simultaneously assesses the kidneys and bladder. • Magnetic resonance imaging: MRI provides excellent images of superficial and deep tissue planes, cavitation of the uterus and presence of a cervix. • Laparoscopy: Laparoscopy provides only indirect assessment of uterine cavitation. It is useful when uterine remnants or endometriosis cause cyclic pelvic pain requiring excision. MANAGEMENT The ideal repair provides the patient with an unscarred vagina that allows sexual functioning. Excision of uterine anlage can also prevent endometriosis and resultant ovarian function impairment. Frank technique or perineal dilation is the only nonsurgical option and is successful only in patients with a long rudimentary vagina. Patients apply progressive pressure to the perineum using a bicycle-seat stool to hold a dilator in place. Compliance is often poor. The surgical options used are basically to create a neovagina using local skin flaps or/and bowel. The condition has tremendous psychological impact and the help of a psychiatrist is required. PROGNOSIS The patient may have normal sexual functioning after surgical reconstruction. However, conception cannot occur without the aid of artificial techniques.

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GENETIC COUNSELING (Courtesy: Dr Amar Verma, Asso. Prof. Pediatrics Medical College Ranchi, Jharkhand)

DEFINITION In defining the role of the genetic counselor, it is useful to first define genetic counseling. The definition use by the American Society of Human Genetics (1975) is very comprehensive. The American Society of Human Genetics defines2 genetic counseling as a communicative process which deals with the human problems associated with the occurrence or risk of recurrence of a genetic disorder in a family. This process involves an attempt by one or more appropriately trained persons to help the individual or family to: (i) Comprehend the medical facts including the diagnosis, probable course of disorder and the available management; (ii) Appreciate the way heredity contributes to the disorder and the risk of recurrence in relatives; (iii) Understand the alternatives for dealing with the risk of recurrence; and (iv) Choose the course of action which seems to them appropriate in view of this risk, their family goals, ethical and religious standards and to act in accordance with that decision to make the best possible adjustment to the disorder in an affected family member and/or to the risk of recurrence of that disorder. The four main components of the role relate to: 1. Communication with clients, both to obtain the family medical history necessary to provide the client with reliable information, and convey the genetic information in a meaningful and clear way. 2. Client support, particularly at times of decision-making or particular stress, e.g. after a new diagnosis has been made in the family. 3. Education of clients and other health professionals. 4. Skills, which enable the genetic counselor to interpret research findings for the benefit of clients, and to support or conduct appropriate research. The person who seeks genetic counseling is called the consult and or counsele and the one who gives it is the counselor. In addition to medical specialists, trained persons with various backgrounds like nursing, social work education and psychology can function as genetic counselors. From the definition, it is clear that the objective of genetic counseling is to make the individual or the family to understand the scientific information about the disease, thus helping them to cope with the problem of genetic disorder and to reach a reproductive decision. Indications for Genetic Counseling The common indications for genetic counseling in clinical practice are as follows: 1. Presence of congenital malformation(s) in a child or stillbirth or in a fetus. 2. Mental retardation with or without malformations or dysmorphism. 3. Skeletal dysplasia—Disproportionate short stature. 5. Neurodegenerative diseases, e.g., ataxias, leukodystrophy. 6. Myopathy.

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7. Known genetic diseases, e.g., thalassemias, Wilson’s disease, hemophilia, mucopolysaccharidosis. 8. Down syndrome and other chromosomal disorders. 9. Relatives of a person with chromosomal translocation. 10. Consanguineous marriage. 11. Advanced maternal age. 12. Exposure to known or suspected teratogen during pregnancy. 13. Any disease if it appears familial. 14. Any unusual disease of skin, eyes, bones, or unusual facial features. 15. Deafness. 16. Familial cancers or cancer prone disease. 17. Ambiguous genitalia or abnormalities of sexual development. Those who might particularly benfit may include:  Couples who already have an affected child and wish to paln for future pregnancy.  Individuals having disorders themselves and keen to have a family.  Individuals having an affected close relative and want to know the risk on their own family. Steps in Genetic Counseling Genetic counseling is a multistep process and involves clinical expertise similar to any other medical speciality. The steps are history taking, pedigree construction, examination, diagnosis, counseling and follow up. A standard medical history is required for the proband (affected individual who draws attention to the family) and for other affected persons in the family. Pedigree Next the pedigree (at least 3 generations) is constructed using standardized set of symbols. Direct questions need to be asked for similarly affected individuals, miscarriages, early deaths, consanguinity, major and minor malformations. Examination A complete physical examination and relavent anthropometric measurements are necessary. In a case with dysmorphology correct description of facial features, minor malformations, normal variants need to be noted down. A photographic record of dysmorphic child is essential as it is much better than a lengthy description. Examination of parents may be needed to verify whether a dysmorphic feature (e.g., shape of ears) is of diagnostic significance or a normal familial feature in that family. Investigations and Diagnosis The importance of precise diagnosis for genetic counseling can not be overemphasized as there may be apparently similar looking disorders caused by different genes (genetic heterogeneity)

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or environmental factors. The various hematological, biochemical and imaging investigations suffice many genetic diseases while for some cases specialized tests like chromosomal analysis, enzyme assays, aminoacid levels, or molecular studies may be needed. Indications for Chromosomal Analysis The usual indications for chromosomal analysis include: (i) Confirmation or exclusion of the diagnosis of known chromosomal syndromes, for example Down syndrome; (ii) Unexplained psychomotor retardation with or without dysmorphic features; (iii) Abnormalities of sexual differentiation and development; (iv) Infertility; (v) Two or more than two monogenic disorders in a patient; (vi) Monogenic disorders associated with mental retardation and/or dysmorphic features; (vii) Recurrent miscarriages or still births; (viii) Multiple malformation syndrome; (ix) X-linked recessive syndrome manifesting in a female; and (x) Pregnancy at a risk of aneuploidy because of previous chromosomally abnormal child, maternal serum screening, advanced maternal age, or abnormality detected on fetal ultrasound scanning. There is little point performing chromosomal analysis on patients with single congenital malformation, single gene disorders or with recognizable non chromosomal syndrome. However, a chromosomal analysis of a clinically obvious Down syndrome child is extremely important, because depending on the type of chromosomal anomaly, the risk of recurrence may vary from 1 to 100 percent. DNA Diagnosis As more and more disease related genes are getting mapped and sequenced, the DNA diagnostic tests are becoming available for single gene diseases. Currently DNA diagnosis for Thalassemia, Hemoglobinopathies, Hemophilia, Duchenne muscular dystrophy, Fragile-X-mental retardation and Spinal muscular atrophy are available in India. For providing prenatal diagnosis, the DNA diagnosis of the affected child in the family needs to be done before hand. Investigations of Family Members A careful clinical examination and investigation of parents and family members for mild manifestations can be of great use in genetic counseling as variable expression is characteristic of many autosomal dominant conditions; for example, parents of a child with tuberous sclerosis or neurofibromatosis. If one of the parents is having any feature of tuberous sclerosis, then the risk of recurrence is 50 percent while in case both the parents are normal, there is no significantly increased risk of recurrence. Similarly, a single central incisor in a parent of a child with holoprosencephaly will suggest autosomal dominant inheritance. Syndrome Diagnosis Multiple malformation syndromes with or without mental retardation is an important group of patients needing genetic counseling. With an evergrowing list of syndromes, reaching an exact diagnosis may be difficult. The situation is greatly helped by various computerized databases,

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namely, London Dysmorphology Database and Pictures of Standard Syndromes and Undiagnosed Malformations (POSSUM). Referring to the books giving detailed descriptions of syndromes and diagnostic approaches is also of great help. Counseling Accurate diagnosis is of paramount importance for meaningful genetic counseling. Other requisities are a quiet, comfortable room and adequate time. The counselor should be a good sympathetic listener with good communicative skill. He should give information in simple nontechnical and local language. Counseling needs to include all aspects of the condition and the depth of explanation should be matched to the educational background of the couple. Natural course of the disease and treatment (sometimes only supportive) should be highlighted. The risk of recurrence should be explained, if necessary with the help of diagrams. The risk, for example 1 in 4 should be explained in both ways, i.e. 1 in 4 and 25 percent. It should be made clear that there may be 2 or 3 or more consecutively affected children in a family as chance does not have memory. The probability can be explained by an example of tossing a coin or like. It is often useful to compare this recurrence risk against the general population risk for the condition and for common birth defects. It should be stressed that any family can have children affected with genetic diseases or congenital malformations and parenting such a child or carrier status for genetic disease is not a stigma nor should be considered a discriminating factor. A common misconception about heredity may also need to be dispelled. Postcounseling options-role of counselors is limited to providing options but they must sincerely help the family during investigations and final decision.The last and the most important part of the counseling is about reproductive options. Depending upon the parents judgment about the risk of recurrence, they may go for contraception, adoption, in vitro fertilization or further pregnancy with or without prenatal diagnosis. The family may need to be referred to a genetic center for getting the latest information about the disease and facility for prenatal diagnosis. REFERENCES 1. Anoop Verma. Short Rib Polydactyly Syndrome Type I (Saldino-Noonan Syndrome) Indian Pediatrics 2005; 42:389. 2. Saldino RM, Noonan, CD. Severe throracic dystrophy with striking microlmelia, abnormal osseous development, including spineand multiple visceral anomalies. Am.J.Roentgenol, 1972; 114:257. 3. Nsumoff, P, et al. Short rib Polydactyly (SRP) syndrome type 3. Radiology, 1977; 122:443. 4. Majewski, F, et al. Polysyndaktylie, verkurzte Gliedmassen and Genitalfehlbildugngen: Kennzeicheneines selbastandigen Syndrome? Z. Kinderheilkd, 1971; 111:118. 5. Mareaux P, Lamy M, Robert JM. Le nanisme thantophore. Press Meedicale, 1967; 75:2519. 6. Young RS, Pocharzevsky R, Leonicus JC, et al. Thanatophorus dwarfism and clover leaf skull (Kleeblattschadel), Raidiology, 1973; 106:401. 7. Anoop Verma, HS Gurudatta. Jeune Syndrome; Indian Pediatrics 2004;41:954-55. With permission. 8. Scott, CI. Achondroplastic and Hypochondroplastic dwarfism; Clinical orthopaedic and related research 1976; 114:18. 9. Murdoch JL, Walker BA, Hall JG, et al. 1970. Achondroplasia- a genetic and statistical survey, Annals of Human Genetics, 1070; 33:227.

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10. Salim MA, et al. Effect of beta-adrenergic blockade on aortic root rate of dilatation of in the Marfan syndrome. Am.J. Cardiol 1994; 74:629. 11. Anoop Verma Disorganization-like Syndrome Indian Pediatrics 2003; 40:268. With permission. 12. Smith Recognizable Pattern of Human Malformations, 5th edition, Poland Sequence page 302. 13. Nelsons Text book of pediatrics, 17th edition, Chapter 687, Osteopetrosis, 23333. 14. Anoop Verma, Shirish Yadu; Fibular hemimelia Indian Pediatrics 2003; 40:359. With permission. 15. Anoop Verma, Nirved Jain. Proboscis Lateralis Indian Pediatrics 2005; 42:607. With permission. 16. Smiths Recognizable Pattern of Human Malformation, 5th edition, Bardet-Biedle Syndrome page 590. 17. Color atlas of Congenital Malformation Syndromes, Michael Baraitser and Robin M Winter, Bardet-Biedle Syndrome, 1996; 162. 18. Anoop Verma, Yadu S. Macrodystrophia lipomatosa, Indian Pediatrics, 2003; 40(17):363-64. With permission. 19. Graziano K, Teitelbaum DH, Hirschl RB: Vaginal reconstruction for ambiguous genitalia and congenital absence of the vagina: A 27-year experience. J Pediatr Surg 2002; 37(7):955-60. 20. Rosenberg HK, Sherman NH, Tarry WF: Mayer-Rokitansky-Kuster-Hauser syndrome: US aid to diagnosis. Radiology 1986; 161(3):815-9. 21. Tolhurst DE, van der Helm TW: The treatment of vaginal atresia. Surg Gynecol Obstet 1991; 172(5):40714. 22. Hensle TW, Kennedy WA. Abnormalities of the female genital tract. Pediatric Surgery, V edn. Ed. O’Neill, et al. Mosby 1998; 1819-33. 23. Rimoin DI, Conner JM, Pyretiz RE (Eds): Emery and Rimoin’s Principles of Medical Genetics, 3rd Ed. New York, Churchill Livingstone, 1997; 31:277-767. 24. Cunnigham FG, Gant NF, et al, William’s Obstetrics 21 edn. New York: Mcgraw Hill 2001; 206, 217,940: 978-79. 25. Chakravorty Amit: Screening and Diagnosis of fetal Malformation: Eds: Debdas AK – 1st Edition, 2004; 179-87. 26. Harper PS. Practical genetic counseling, 4th Edition, Butterworth-Heinmann, Oxford 1993. 27. Harper DS, Practical gnetic counseling, 4th Edition USA Butterworth Heinemann. Oxford University Press, 1993 . 28. Phadke SR. et al, Genetic counseling in paediatric practice: Indian paediatric: vol. 36, no. 8, 1999; 789-97. 29. Emery’s elements of Medical genetics, Robert Muller, Ian Young, 10th Edition, Churchill-Livingstone: 237-43. 30. Harper PS. Practical genetic counseling : 4th Edition, Butterworth-Heinemann, Oxord.

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Chapter

9

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TETROLOGY OF FALLOT (Figs 9.1A to D) DEFINITION This is the most common cause of cyanotic congenital heart disease. There are four cardinal features.  Large outlet VSD.  Overriding aorta with respect to the ventricular septum.  Right ventricular outlet obstruction (infundibular vavular pulmonary stenosis).  Right ventricular hypertrophy. SYMPTOMS  Most of the patients are diagnosed in the first two-month of age following identification of murmur. Few patient present with severe cyanosis the first few days of life.  The classical description of severe cyanosis, hypercynotic spells and squatting on exercise developing in late infancy is now rare.  It is important to recognize hypercynotic spells, as they may lead to myocardial infarction, cerebrovascular accidents and even death if left untreated. They are characterized by a rapid increase in cyanosis, usually associated with irritability or inconsolable crying, because of severe hypoxia, and breathlessness and pallor because of tissue acidosis. SIGN  Clubbing of the fingers and toes in older children.

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C

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B

D

Figs 9.1A to D: Tetrology of Fallot (A) Ten-year-old child with clinically obvious central cyanosis (B) Clubbing of fingers (C) Classical X-ray finding consistent with wooden shoe or boot shaped “Coeur en sabot” heart (D) Peculiar position in bed during sleep, similar to sqatting episode adopted by patient

 A long, loud ejection systolic murmur is best heard in the third left intercostals space, usually with single second heart sound.  As with increase in right outflow tract obstruction the murmur will shorten and cyanosis will increase. INVESTIGATION Chest X-Ray Shows upturned cardiac apex, absent pulmonary shadow at the left cardiac border, oligemic lungs field with right aortic arch in few cases. ECG Shows right axis deviation and right ventricular hypertrophy.

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Echocardiography This will demonstrates the cardinal features. But cardiac catheterization may be required to show the detailed anatomy of pulmonary arteries, which may be small or stenosed. CT Scan In case cerebral abscess is suspected. MANAGEMENT Palliative Surgery Infants who becomes symptomatic in first few month. Surgery is inclined to improve pulmonary blood flow. This is done by placement of an artificial tube between the subclavian artery and the pulmonary artery (Modified Blalock-Taussig shunt). Corrective Surgery It is performed around six months of age. It involves closing the VSD and relieving right ventricular outflow tract obstruction with an artificial patch. The operative risk is approximately 2 to 5 percent. Managing Cyanotic Spells Hypercyanotic spells are usually self limiting and followed by a period of sleep. If it is prolonged more than 15 minutes, should require prompt treatment.  Sedation and pain relief (morphine is excellent).  Knee chest position—In small infant this can be achieved by strapping the bent legs to the abdomen (Squatting while supine).  Intravenous propranolol, which probably works both a peripheral vasoconstrictor and by relieving the subpulmonary muscular obstruction that is the cause of reduced pulmonary blood flow.  Sodium bicarbonate: 1ml/kg of 7.5 percent solution after establishing oxygen to correct acidosis. PREVENTION OF FUTHER EPISODES  Prevention of precipitating factors treating fever and dehydration on time and adequately.  Correct anemia with iron.  Beta-blockers. Oral propranolol 2 mg/kg/d in four divided doses continued till surgery. The dose should be increased till the heart rate is reduced to minimum possible heart rate for age up to 4 mg/kg/d.  Prophylaxis for endocarditis is mandatory.

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CONGENITAL PTOSIS (Fig. 9.2)  Congenital drooping of one or both eyelids is relatively common, Unilateral being 70 percent out of all.  Etiology is unknown but it doesn’t have familial tendency.  Congenital ptosis is easily missed in early childhood and is picked up late in life and is often labelled as acquired.  It is sometime associated with miosis which raises the possibility of Horner’s syndrome.  It is also an association with Jaw winking phenomenon or Marcus gun phenomenon.  Congenital ptosis has to be differentiated from acquired ptosis. Miosis responds with pharmacological agents in congenital ptosis and also not associated with any extra ocular muscle paresis.  Management—Early corrective surgery is useful in elevating the lid to improve the appearance.

Fig. 9.2: Left congenital ptosis

CONGENITAL CATARACT (Fig. 9.3)  The presence of cataract with in first three month of life is said to be congenital cataract.  In about one third cases the cause is intrauterine infection, but at present this percentage is declining due reduction in rubella embryopathy.  In another one-third cases cataract is due to genetic and chromosomal disorders. Around 10 percent in trisomy 13 and 18 and 21.  The patient of Turner’s syndrome, cataract appears in 40 percent cases by puberty.  Clinically small cataracts are not easily detected. Large cataract occupies the pupil and hampers the vision. Cataract may remain stationary and often progresses.  Always search for other congenital anomalies like aniridia, coloboma, and microphthalmia as it is seen in 40 percent cases.  Diagnosis of congenital cataract depends on its etiology.  Management—Removal of congenital cataract before age Fig. 9.3: Congenital cataract of three month is important to prevent amblyopia.

PERIORBITAL CELLULITIS (Fig. 9.4)  Basics—The orbital septum is a fibrous membrane running from the periosteum of the orbital bone to the tarsal plates. It separates the skin and subcutaneous tissue from intraorbital structures. Although the clinical picture is structures are similar, differentiation of periorbital (preseptal) cellulitis from orbital (postseptal).  Clinical features—Both periorbital and orbital cellulitis presents with warm, tender, erythematous lid swelling, usually associated with fever and regional lymphadenopathy.

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 Periorbital cellulitis—The infection may spread by a break in the skin (insect bite, laceration, impetigo), with causative agents being S.aureus or group A Streptococcus. The infection may spread commonly from ethmoid sinus with M.catarrhalis, pneumococcus. In sinusitis related cases there is history of persistent nasal discharge and the upper eyelid may be affected first and subsequently lower eyelid is affected. There is mild to moderate conjunctival swelling and hyperemia with a mucoid to purulent discharge.  Orbital cellulitis—The hallmark of a postseptal infection is proptosis, chemosis and decreased extracellular mobility in association with fever. Decreased visual acuity occurs Fig. 9.4: Periorbital cellulitis late in the course.  Both these clinical condition has to be differentiated from each other, because more aggressive management is required in orbital cellulitis. Passively open the eyelid and look for conjunctival injection, discharge, proptosis, chemosis, and decreased extraocular mobility and check visual acuity. A non-contrast CT scan is needed to differentiate periorbital and orbital cellulitis if not possible clinically.  Management Periorbital cellulites—Appropriate antibiotic like cephalexin, cephadroxyl, cefuroxime, etc. along with warm compresses four times. In cases of orbital cellulites the patient requires admission and intravenous antibiotic and close monitoring.

RHINOSPORIDIOSIS (Figs 9.5A and B)  It is caused by yeast like organism, Rhinosporidium seeberi, which infects the mucous membrane of the nose, producing nasal polyps and tumors of the cheeks, conjunctiva, lacrimal sac, uvula, ear, glans penis and skin.  Friable, highly vascular, sessile and pedunculated polyps may appear on any mucosal surface, but rarely on the skin.

A

B Figs 9.5A and B: Rhinosporidiosis of conjunctiva (A) (B) Note the sessile mass projecting out from the upper conjunctiva

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 When the face and lids are involved, it has to be differentiated from yaws, blastomycosis and leishmaniasis. Masses of pedunculated, granulomatous polyps containing the fungus produces painless deformities (unless there is secondary infection) any discharge. The external ocular membrane and lacrimal passage are readily involved. Even the sclera has been known to be infected, with the threat of perforation of the eye.  Diagnosis is made by demonstration of sporangia up to 350 mew micron in diameter in section of excised tissue. Treatment is essentially surgical.

VITAMIN A DEFICIENCY (Figs 9.6A and B)  Deficiency of vitamin can occur from deficient diet, decreased absorption due to chronic intestinal disorders and liver diseases, increased requirement in case of infection. Bitot’s spots has prevalence of 0.21 percent in all age group in India. Vitamin A deficiency contributes to 0.04 percent of all blindness.  Clinical features: • The first symptom of vitamin A deficiency is delay in dark adaptation. • Conjunctival xerosis is first clinical sign, which is obvious. The conjunctiva becomes dry, lusterless and dirty brown in the interpalpebral bulbar conjunctiva. This later on gives rise to Bitot spot, which is a triangular area of foamy substance on the temporal area of conjunctiva. It is composed of heaped up sloughed-off keratinised cells and saprophytic bacilli which collects on conjunctival sac • Keratomalacia is seen in late stage and consists of softening, necrosis and ulceration of conjunctiva. The WHO classification of Xerophthalmia is depicted in table. • The extraocular manifestation includes follicular hyperkeratosis, toad skin and phrynoderma. Squamous metaplasia of epithelium is seen as increased susceptibility of infection. • The diagnosis of vitamin A deficiency is considered in the presence of clinical signs and serum retinal level of less than 20 mg/dl.

A

B Figs 9.6A and B: (A) (B) Bitot’s spots

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Primary sign

XIA XIB X2 X3A

Conjunctival xerosis Bitot spot Corneal xerosis Corneal ulceration Secondary

XN XF XS

•

•

Night blindness Fundal changes Corneal scarring

Treatment- According to WHO xerophthalmia is treated by giving 2,00,000 IU of vitamin A is given orally on presentation, the following day, and whenever possible, 1-4 week later. Infants between age group 6 and 12 month should receive the half dose and infant less than 6 months one quarter of the dose. National Program on prevention of blindness- recommends 1,00,000 IU of vitamin A orally between 6 and 11 month preferably at the time of measles vaccination. And children between 1 and 5 years should receive 2,00,000 IU of vitamin A every six month.

GEOGRAPHIC TONGUE (Fig. 9.7) It is benign migratory glossitis, is a self-limiting disease of unknown etiology. It presents as pink to red, round and irregular shaped area of dekeratinized and desquamated papillae, with white or yellow elevated margin in the dorsal and lateral surfaces of the tongue and a changing pattern (hence, the name). It is asymptomatic but may be painful when inflamed. Fig. 9.7: Benign migratory glossitis (Geographical tongue)

FISSURED TONGUE (Fig. 9.8) It is congenital malformation manifested by presence of multiple fissures on the dorsal aspect of the tongue. Adequate oral hygiene and regular brushing of the tongue in important to reduce the bacterial growth within the fissures.

Fig. 9.8: Fissured tongue

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FOREIGN BODY NOSE (Figs 9.9A and B)  Foreign body found in the nose commonly includes inanimate objects (toys, ear rings, etc.) vegetable materials and insects.  Nose being the most common site of foreign body impaction in children under three years of age.  Unfortunately the sign and symptoms of foreign body nose may be subtle and there may be no clear-cut history of insertion.  Clinical features: It usually presents as unilateral fowl smelling discharge with unilateral obstruction. The object can be seen in the nose anteriorly, but swelling of the mucosa can obscure visualization.  Management: Most of the foreign body becomes impacted between the anterior nasal septum and inferior turbinate. Prior to attempting, restrain the child, and under local anesthesia spray using 4 percent lidocaine, gentle suction is applied to clear the field. Use nasal speculum and with alligator forceps the object is removed. Routine use of nasal decongestants and antibiotics are not required.

A

B

Figs 9.9A and B: (A) Patient with unilateral nasal discharge, retracted right nostril is depicting foreign body inside it. (B) A piece of sponge was taken out from the right nostril

INGESTED FOREIGN BODY (Figs 9.10A and B)  Children swallow an object accidentally e.g. coin, nail small button batteries, etc.  Retrosternal pain, dysphagia, and drooling of saliva may follow or be the presenting complaints.  Physical sign are usually absent, but the tenderness in the low anterior neck may accompany high impaction.  Plain AP and Lateral X-ray will show densely opaque foreign bodies (coin) or less opaque objects in a dilated esophagus. The X-ray should include the neck, as the upper esophagus lies at a level above the sternum.  Removal: By flexible or rigid endoscope, but in both the cases the appropriate grasping instruments must be available. After removal it is important to inspect the esophagus and stomach for any residual damage.

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A

B

Figs 9.10A and B: (A) Ingestion of coin at upper esophagus. (B) Foreign body nail in the duodenum

 Button batteries ingestion poses additional problems, as leaking alkali can ulcerate and perforate the esophageal wall, and leaking mercury is toxic if absorbed. Removal from esophagus is, therefore, important and onward passage through the gut (if the battery has reached the stomach) should be encouraged with metachlorpram.

FOREIGN BODY ASPIRATION (Figs 9.11A to C)  Experimental play easily leads to accidental aspiration or ingestion of foreign bodies in the toddler and young child. Boys are more prone to do this than girls.  All types of small foreign bodies are able to pass through the upper airway and cords and lodge in the trachea or main bronchus. Tacks, screws, plastic beads and pen-tops, peanuts and seeds are common culprits. The essential aspect in timely diagnosis of this potentially life threatening events is high index of suspicion.  The history is always acute. Spasms of coughing may be associated with stridor, retching and vomiting. Dyspnea and cyanosis may coexist.  If on presentation, the child has evidence of serious airway obstruction, an immediate attempt to remove the foreign body may be necessary without the confirmation of its presence of site.

A

B

C

Figs 9.11A to C: Foreign body bronchus (A) X-ray chest of patient presented with chronic cough with no history of aspiration, revealed collapse right lower lobe (B) In spite of an adequate antibiotic for 10 days repeat X-ray shows almost no change, which gives us an indication for diagnostic bronchoscopy (C) Small peanut taken out from right lower bronchus

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•

Heimlich maneuver: It involves embracing the child’s trunk from behind just below the rib margin and producing a rapid squeeze with the object of causing a forceful expulsion of air and foreign body from the lungs. This may be aided by holding the child upside down. The risk of this procedure is that the foreign body may be forced from a bronchus only as far as the trachea and result in even more severe obstruction.  Diagnosis: Foreign body impaction produces various symptoms and sign, depending on its site, duration and extent. • Stridor (inspiratory) and wheeze on auscultation; • Hyper-resonance and overinflation due to air trapping; • Displaced apex beat due to mediastinal shift; • Collapse and consolidation if obstruction is complete and prolong.  Investigation – get an X-ray chest PA view in inspiration and expiration. The hyperinflation of the lung fields is seen due to air trapping on the affected side in expiration. The foreign body aspiration is much more common on right side.  Bronchoscopy – a rigid pediatric bronchoscope with grasping forceps is needed to remove the foreign body under general anesthesia. Occasionally emergency tracheotomy is sometime required.

PALATAL PERFORATION1 (Fig. 9.12)  The incidence of syphilis is rising worldwide. In the UK the number of new diagnoses increased by over 900 percent between 1996 and 2002. The resurgence is most marked in homosexual men and a series of large outbreaks have occurred particularly in London but also Manchester, Brighton, Newcastle-upon-Tyne, Dublin and Scotland. Recent interest has focused on the altered presentation in HIV positive men who are at greater risk of tertiary stage syphilis and have thus, increased the likelihood of clinicians witnessing its signs and symptoms.  Mechanism of damage: Syphilis is caused by the spirochaete Treponema pallidum and may be congenital or acquired.Transmission can occur via direct contact with syphilitic lesions or infected blood. Entry is gained through epithelial breaks and spread occurs via the lymphatic and circulatory systems. The incubation period lasts from 10 to 90 days after which the first two stages are highly contagious. Tertiary syphilis develops 3 to 10 years later in 30 to 40 percent of patients. It results from reactivation in an untreated or inadequately treated person or from reinfection in somebody previously treated. All features arise from endarteritis obliterans.  Clinical features: Three stages of syphilis are usually described. Each is associated with characteristic oral lesions. Primary syphilis uncommonly manifests as an oral chancre. Secondary syphilis can cause greyish ulceration in ‘snail track’ or ‘mucous patch’ formations. Tertiary syphilis is a non-infective multi-organ stage characterized by a painless localized granuloma (gumma)1 which classically presents on the midline of the palate. Degradation of the mass leaves a deep pale ulcer with necrotic rolled margins. Chronic necrosis destroys the palatal bone to leave a clean perforation. Healing occurs with severe scarring which causes distortion or destruction of the soft palate and tongue. Systemic complications most seriously affect the cardiovascular and nervous systems. Aortic aneurysms, as seen in this case, are rarely seen.

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 Diagnosis: The gumma is a granulomatous lesion characterized by endarteritis obliterans and the absence of scar tissue contracture. Histological changes can be non-specific and do not therefore form the basis of diagnosis. Non-specific serological testing (e.g. VDRL) indicates active disease and is positive in untreated tertiary syphilis. Specific tests (e.g. FTA) remain positive even in treated cases. Other tests may be appropriate at different stages. Testing normally extends to current and recent partners and also checks for other STDs.  Management is two-fold as it requires treatment of the underlying problem and local treatment of the perforation. Referral to a Genitourinary physician is necessary for treatment of syphilis. Penicillin forms the mainstay of treatment and is supported with preventive advice and regular sexual health check- Fig. 9.12: Palatal perforation in a patient suffering from tertiary syphilis ups. Treatment of late syphilis will not reverse the tissue damage but it may result in some improvement. Dental management can resume once the VDRL is negative.  Specific management of the palatal defect may be to do nothing, to seal the defect or to repair the defect. Obturators are a successful method of managing the speech and masticatory problems. Surgery is another option but extensive scarring in syphilitic lesions makes any attempt at palatal repair hazardous. In cocaine abusers surgical intervention should be delayed for at least one year following confirmation of drug cessation and lesion stability. The patient should remain under review to check for progressive necrosis. Reconstruction is again controversial due to the etiology of tissue damage. Ischemia and necrosis render the tissues more likely to breakdown following surgical repair. The better option seems to be the non-surgical conservative approach.  Differential diagnosis of palatal perforation. Group Trauma Infections Neoplasia Collagen disease Idiopathic Other

Examples Tuberculosis, tertiary Syphilis, typhoid, diphtheria, mucormycosis, actinomycosis. Lymphoma, carcinoma, melanoma Wegener’s granulomatosis, SLE Midline lethal granuloma Cocaine abuse

EXTRAVASATION INJURY (Figs 9.13A to D)  Extravasation injury is defined as injury caused by intravenous fluid (IV) in the interstitial space.  IV infiltration can have spectrum of sequelae.

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A

B

C

D

Figs 9.13A to D: Extravasation injury (A) Gangrene of left great toe and third toe secondary to femoral artery puncture (B) Gangrene of toes of both feet (C) Extravasation of intravenous fluid causing injury and edema of dorsum of hand (D) Erythema and cellulitis of temporal skin seondary to extravasation of fluid from scalp vein needle

• Mild reaction including irritation, Erythema and swelling. • Severe infiltration can lead to life threatening ischemia and need for amputation.  Mechanism of damage • The extravasation of normal saline or 5 percent dextrose solution can cause irritation and pain at the IV site but does not cause significant tissue loss. • Tissue damage may be result of direct cellular injury. Solutions such, as hyperalimentation, that has an osmolarity greater than serum can alter the osmotic gradient leading to intracellular fluid overload or dehydration and subsequent cell death and necrosis. • Potassium and Calcium are dangerous as they are not only hypertonic but also causes precipitation of protein, leading to cell death. • Chemotherapeutic agents often cause injury due to cytotoxic mechanism. • Vasoconstriction leading to tissue ischemia by drugs causing vasoconstriction does cause extravasation injury.  Immediate treatment: Once extravasation has occurred immediate treatment should be instituted. • IV therapy should be ceased. • Elevate the limb. 2 percent of 1,800 extravasation injuries progressed to tissue loss if immediately diagnosed and treated properly. • Application of intermittent ice when combined with conservative measurement was successful in 85 percent of injuries due to chemotherapeutic agents. • The use of heat and ice is controversial in neonate neither is useful because of tissue damage. • Wound management depends on whether there is full thickness (with or without eschar formation) or partial-thickness tissue loss, characterized by blistering and discoloration. • Silver sulfadiazine is advocated for both partial and full thickness wounds. Betadine and normal saline dressings can also used.  More aggressive intervention: Some author advocates the measure to counteract the effects of the extravasated material or physically removes from the tissue. • Despite a sizable body of literature, the use of antidote to infiltrated therapeutic agents remains controversial. The table lists the accepted treatment for number of frequently extravasated medication. Hyluronidase, phentolamine and nitro-glycerine are the most common.

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HYALURONIDASE  It is an enzyme that degrades interstitial bonds, thus facilitating diffusion and absorption of the extravasated fluid.  It is used to counteract wide variety of infiltrated substance.  The usual dose is 15 U/ml administered in aliquots of 0.2 mL around the periphery of the area of infiltration. PHENTOLAMINE  An alpha-adrenergic antagonist that has shown to counteract the vasoconstrictive effects of infiltrated vasopressor such as dopamine and dobutamine.  The dose is 5-10 mg/10 ml of normal saline injected in 0.5 mg aliquots. NITROGLYCERIN  Topical nitroglycerin has been shown to counter act the vasoconstrictive contribution to tissue necrosis.  The dose is 4 mm of 2 percent ointment per kg body weight. Treatment of specific infiltrated substance2 Medication

Treatment

Dose

Aminophylline Calcium Dextrose 10%

Hyaluronidase15U/ml Hyaluronidase15U/ml Cold compresses Hyaluronidase15U/ml Nitroglycerin oint 2% Hyaluronidase15U/ml Phentolamine- in neonate Dilute 2.5 – 5mg in 10 ml All others- dilute 5-10 mg In 10 ml of NS. Nitroglycerin oint 2% Hyaluronidase15U/ml Hyaluronidase15U/ml Hyaluronidase15U/ml Hyaluronidase15U/ml Hyaluronidase15U/ml Phentolamine- in neonate Dilute 2.5 – 5 mg in 10 ml All others- dilute 5-10 mg In 10 ml of NS. Nitroglycerin oint 2%

0.2 ml × 5 doses 0.2 ml × 5 doses QID × 72 hrs. 0.2 ml × 5 doses 4 mm/kg 0.2ml × 5 doses in neonate – multiple SQ not to exceed 0.1mg/kg or 2.5 mg all others –multiple 0.5 mg Inj not to exceed 10 mg. 4 mm/kg q8hr 0.2 ml × 5 doses 0.2 ml × 5 doses 0.2 ml × 5 doses 0.2 ml × 5 doses 0.2 ml × 5 doses in neonate – multiple SQ not to exceed 0.1 mg/kg or 2.5 mg all others –multiple 0.5 mg Inj not to exceed 10 mg 4 mm/kg q8hr

Diazepam Dobutamine and Dopamine

Gentamicin Mannitol Phenytoin Potassium salt Sodium bicarbonate Epinephrine

*Soft Tissue infiltration injury 412-424—Manual of Neonatal Surgical Intensive Care, AR Hansen and M Puder, 2003.

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INTRAOSSEOUS TRANSFUSION (Fig. 9.14) This provides fast and reliable vascular access in critically ill children. It remains available even in shock and is indicated in an emergency when other methods are unavailable or unsuitable e.g. in burns cases. Guidelines are that during CPR in children aged < 6 years should obtain intraosseous access if cannot achieve reliable venous access after three attempts or 90 secs, whichever comes first. Intraosseous access has the same benefits in children over 6 years but access to the anterior tibial marrow is more difficult and other sites such as the lower femur, iliac crest or sternum should be considered.

Fig. 9.14: Intraosseous transfusion in an 11-month-old patient presented is shock due to dehydration

 Complications are rare and include subcutaneous fluid leakage, extravasation from the puncture site, damage to the bone and infection.  Relative contraindications include fractured limb, local infection or osteomyelitis severe bone disease, especially osteogenesis imperfecta.  Can achieve high flow rates especially if using a syringe to infuse fluid.  Can give all resuscitation fluids except bretylium. Gaining intraosseous access: Ideally a sterile procedure using a custom designed needle. However, can use bone marrow aspiration needle or any 14-20-gauge needle with an internal stylus in an emergency.3,4  Palpate the access site 2-3 cm distal to the tibial tuberosity on the flat medial surface of the tibia.2  Prepare skin and infiltrate with lignocaine, if necessary.  Advance needle at 90 degrees through the bone cortex using firm pressure and a rotary motion (entry into the marrow cavity is felt as a loss of resistance).  Confirm placement by flushing with saline, which should produce free flow with no evidence of subcutaneous extravasation.  Connect to infusion set with a short extension and three-way tap to reduce traction on needle. Immobilize access with a dressing and tension relief with adhesive tape between legs and infusion set.  Obtain venous access as soon as adequate resuscitation achieved.

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SICKLE CELL DISEASE (Figs 9.15 to 9.18A and B) (Courtesy by Dr Jyotish Patel, MD, Bardoli, Gujrat, Dr Amar Verma, MD, RIMS, Ranchi, Jharkhand )

 Sickle cell disease comprises a group of genetic disorders characterized by the inheritance of sickle hemoglobin (HbS) from both parents, or HbS from one parent and a gene for an abnormal hemoglobin or beta-thalassemia from the other parent. The presence of HbS can cause red blood cells to change from their usual biconcave disc shape to a crescent or sickle shape during deoxygenation. Upon reoxygenation, the red cell initially resumes a normal configuration, but after repeated cycles of “sickling and unsickling,” the erythrocyte is damaged permanently and hemolyzes. This hemolysis is responsible for the anemia that is the hallmark of sickle cell disease.  Acute and chronic tissue injury can occur when blood flow through the vessels is obstructed by the abnormally shaped red cells. Complications include painful episodes involving soft tissues and bones, acute chest syndrome, priapism, cerebral vascular accidents, and both splenic and renal dysfunction. Common causes of mortality among children with sickle cell disease include bacterial infections, splenic sequestration crisis Fig. 9.15: A child with Sickle cell disease having generalized body pain. Observe facial discomfort and acute chest syndrome. due to severe pain Types The percentage of HbS is helpful for determining type of sickle cell anemia.  Sickle trait, not a disease ——— HbS approx 40 percent  Sickle cell disease HbSC, HbSD, etc. —— HbS approx 50 percent  Sickle cell disease HbS-beta-plus-thalassemia ——— HbS approx 70 percent  Sickle cell disease HbSS, HbS-beta-zero-thalassemia —— HbS approx 95 percent However, for the subtypes of sickle cell disease like HbSC, the important fact is that the other Hb is able to participate in polymerization with HbS. Difference in Sickle Cell Trait and the Different Types of Sickle Cell Disease? Sickle trait can have microscopic hematuria or slight increase in kidney infections. Individuals with sickle trait can have pain if they go to very high altitudes, greater than 12,000 feet. Other than these uncommon problems, there should be not health problems from sickle trait. Individuals with sickle trait may have children with sickle cell disease if their partner also has sickle, thalassemia, or hemoglobin C trait. People with sickle trait have one gene making HbS and one gene making HbA, so one would expect equal amounts of HbS and HbA in the RBC. The unstable property of HbS, however, means that not the entire amount of HbS made in the red blood cell (RBC) stays floating around in the RBC, because some of the HbS decomposes. Therefore, the RBC contents for a person with sickle trait has slightly less than 50 percent HbS, typically something like 55 to 60 percent HbA and 40 to 45 percent HbS. The predominance of

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HbA inhibits and dilutes the ability of HbS to show its polymerization property, and so sickle trait is not a form of sickle cell disease. People with sickle trait have no anemia, no painful episodes, no special susceptibility to infection, and no implications for life expectancy. Life Expectancy in Sickle Cell Disease5 Median survival of individuals of all ages with sickle cell disease based on genotype and sex.1 Males with Hb SS – 42 years Females with Hb SS – 48 years Males with Hb SC – 60 years Females with Hb SC – 68 years Note that this was reported in 1994. Now in 2002 many new advances with the medication hydrea, the new pneumoccocal vaccine Prevnar, stroke prevention with TCD, and cures with bone marrow transplants the life expectancy is increasing. Being 50 Years Old with Sickle Cell Disease. Symptoms The clinical course of sickle cell anemia does not follow a single pattern; some patients have mild symptoms, and some have very severe symptoms. The basic problem, however, is the same: the sickle-shaped red blood cells tend to get stuck in narrow blood vessels, blocking the flow of blood. This results in the following conditions: Hand-foot Syndrome When small blood vessels in hands or feet are blocked, pain and swelling can result, along with fever. This may be the first symptom of sickle cell anemia in infants. Fatigue, Paleness, and Shortness of Breath These are all symptoms of anemia or a shortage of red blood cells.

Fig. 9.16: A patient with Sickle cell disease had severe abdominal pain. Surgeon thought it due to acute appendicitis. He was operated and pain did not disappear after surgery. He was referred for expert opinion. He was a case of Sickle cell disease (SS) with painful crisis. He recovered with medical line of treatment

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Fig. 9.17: On right is an elder brother with SS, he is primary teacher. Younger sib also has SS, he studies in 9th std. Family responsibility lies with elder one alone. Parents are old. Economic crisis is a major threat for regular follow-up

Pain that Occurs Unpredictably in Any Body Organ or Joint A patient may experience pain wherever sickled blood cells block oxygen flow to tissues. The frequency and amount of pain vary. Some patients have painful episodes (also called crises) less than once a year, and some have as many as 15 or more episodes in a year. Sometimes pain lasts only a few hours; sometimes it lasts several weeks. For especially severe ongoing pain, the patient may be hospitalized and treated with painkillers and intravenous fluids. Pain is the principal symptom of sickle cell anemia in both children and adults.

A

B

Figs 9.18A and B: Sickle cell arthropathy (A) Look at bent little finger on both side. (B) Shortening of left lower limb due to avascular necrosis of head femur

Eye Problems The retina can deteriorate when it does not get enough nourishment from circulating red blood cells. Damage to the retina can be serious enough to cause blindness. Jaundice Jaundice is seen due to chronic hemolysis. Delayed growth and puberty in children – is caused by chronic anemia.

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MANAGEMENT ISSUES6 Acute illness in sickle cell disease: Acute illness is characterized by any of the following sign and symptoms listed below. 1. Temperature > 38.5°. 2. Pain inadequately relieved by home measures. 3. Significant respiratory symptoms. 4. Abdominal pain, distension and acute enlargement of spleen. 5. Any neurological sign and symptoms. 6. Significant increase in pallor, fatigue or lethargy. 7. Priapism episode persisting > 3-4 hr 8. Significant diarrhea and vomiting. Pain Management Mild to moderate  Acetaminophen with codeine 1 mg/kg po (then q 4hr) and oral fluids.  Consider starting ibuprofen 10 mg/kg po q 6-8 h or other anti-inflammatory agent if no contraindication present. Limit more frequent dosing to 72 hrs duration. Moderate to severe  Morphine 0.1-0.15 mg /kg IV. Reassess the pain q 15-30 min. Patients with severe pain may require repeated doses of morphine 0.02-0.05 mg/kg IV q 15-30 min.  Alternative analgesic such as hydromorphine 0.015-0.02 mg/kg IV may be appropriate.  Ketorolac 0.5 mg/kg (30 mg maximum dose) IV may be used. Do not use ibuprofen with ketorolac. Fluid of choice in prevention of Painful crisis: We recommend water as the drink of choice during an episode of sickle cell pain. The rationales are: 1. Sickle red blood cells tend to be dehydrated, 2. Test tube studies show that adding water to the sickle red blood cell can lower the hemoglobin concentration and decrease sickle polymer formation. 3. A study from the 1960’s showed that giving IV fluid without electrolytes (5% dextrose in water, abbreviated D5W) or low in electrolytes (D5 1/4 normal saline) was better than IV fluid with electrolytes for sickle cell crisis patients hospitalized for crisis. 4. Kidney damage from sickle cell makes it harder to excrete sodium than the average person, so that continuously adding too much salt to the body may worsen the dehydration of the sickle red blood cells and increase sickle polymer formation. 5. Too much water given IV (in the vein) may cause problems with edema of the lungs or brain, so IV overhydration is not a good idea. A combination of IV and oral fluid intake is preferred, because the patient’s hormonal control of thirst can keep electrolytes and volume from getting too far out of line.

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Blood Transfusion Therapy for Acute Complications Indications  Acute exacerbation of base line anemia. • Aplastic crisis • Sleenic sequestration • Hepatic sequestration • Hyperhemolysis  Severe vaso-occlusive events • Acute chest syndrome • Stroke • Severe infection • Acute multiorgan failure syndrome  Preparation for procedures • General anesthesia • Radiographs with ionic contrast. Choice of transfusion products: Leukocyte depleted, packed red cell are recommended. Where available, minor- antigen-matched, sickle-negative cells are preferred. Volume considerations: Simple transfusion with 10 cc/kg of packed RBC typically raises the hemoglobin level to about 2 gm/dl. Patients with aplastic crisis where anemia develops over several days volume over load has to be watched, in such cases, Packed cells 4-5cc/kg has to be planned along with frusemide. Hyperviscocity: A simple red cell transfusion that increases the hemoglobin levels to >10-11gm/ dl posses the risk of hyperviscocity, especially when the baseline hemoglobin level are more. Management of vaso-occlusive pain: The vaso-occluive pain has to be controlled as mentioned above. Antibiotics as Cefotaxime or cefuroxime 50 mg/kg IV q 8 hrly if febrile. Substitute clindamycin 10 mg/kg IV q 6 hrly for known or suspected cephalosporin allergy. Consider Vancomycin in severe infection or suspected CNS infection. Oxygen by nasal cannula to keep saturation above 92 percent, avoid excess of oxygen to avoid suppression of reticulocyte count and aggravation of anemia. The analgesics may be weaned as tolerated by decreasing dose, not by prolonging the interval between doses. HOW TO DIFFERENTIATE ?? V.O. CRISIS v/s SEQ.CRISIS

Fig. 9.19: In vaso-occlusive crisis liver and spleen size will decrease. In sequestration crisis liver and spleen size will be enlarged

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Management of acute chest syndrome: An acute chest syndrome is defined as acute illness associated with lower respiratory symptoms, hypoxemia, or new infiltrates on CXR. It is managed by supplementation of Oxygen to keep oxygen saturation above 92 percent. Analgesics like acetaminophen or ibuprofen or morphine according to severity of pain. Antibiotics like Cefotaxime or cefuroxime 50 mg/kg IV q 8 hrly if febrile. Substitute clindamycin 10 mg/kg IV q 6 hr for known or suspected cephalosporin allergy. Strongly consider adding Vancomycin 10-15 mg/kg IV q 8 hr for severe illness like large infiltrate or pleural effusion. Consider bronchodilator if wheezing is present. Blood transfusions and positive pressure ventilation as per required in individual cases. Management of acute splenic sequestration: An acute illness associated with hemoglobin 2gm/ dl or more below patient’s base line value with acutely enlarged spleen. Mild to moderate thrombocytopenia is often present. Retics count equal or greater than base line. A low retics count indicate coexisting aplastic crisis. Apart from the other aspects of management like antibiotics, oxygen and vital monitoring, it is managed by transfusion of packed red cells 10 ml/ kg for hemoglobin < 4 –5 gm /dl and/or signs of cardiovascular compromise. A post transfusion level of hemoglobin should be 8-9 gm/dl to avoid the hyperviscocity that may occur several days’ later sequestrated red cells return to the circulation. Hydroxyurea: The first effective drug treatment for adults with severe sickle cell anemia was reported in early 1995, when a study conducted by the National Heart, Lung, and Blood Institute showed that daily doses of the anticancer drug hydroxyurea reduced the frequency of painful crises and acute chest syndrome. Patients taking the drug needed fewer blood transfusions. Sickle Cell Anemia and Current Research 7,8 The oxygen requirements of a fetus differ from those of an adult, and so perhaps not surprisingly, prenatal blood contains a special hemoglobin. Fetal hemoglobin contains two gamma γ globin polypeptide chains instead of two adult β chains. After birth, the genes encoding γ globin switch off, and the ones encoding β globin switch on. Understanding how this genetic switch works could allow researchers to understand much about the control of genes in general and sickle cell anemia in particular. Some infants whose mothers suffered from diabetes during pregnancy have unusually high concentrations of the biochemical butyrate in their blood plasma. Butyrate is a natural fatty acid that stimulates RBCs to differentiate from their precursors (reticulocytes). Butyrate also prevents the γ globin gene from switching off and the β globin gene from switching on in these infants, who are healthy despite lacking adult hemoglobin. When butyrate is given to patients β globin mRNA levels in reticulocytes increase significantly. Perhaps butyrate or other chemicals (Decitibine, Magnesium sulphate, Clotimazole, Poloxamer 188, Nitirc oxide) that stimulate fetal hemoglobin production could be used to treat sickle cell anemia.

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REFERENCES 1. British Dental Journal 2005;199:267-69. doi: 10.1038/sj.bdj.4812650. 2. Care of the Critically Ill Child. Macnab A et al. Churchill Livingstone. 3. Boon JM, Gony DL, Meiring JH. Finding an ideal site for intraosseous infusion of the tibia: an anatomical study. Clin Anat 2003;16(1):15-8.[abstract] 4. Daga SR, Gosavi DV, Verma B. Intraosseous access using butterfly needle. Trop Doct 1999;29(3):1424.[abstract] 5. Platt OS, Brambilla DJ, Rosse WF, et al. Mortality in sickle cell disease- Life expectancy and risk factors for early death. N Engl J Med 1994; 330(23):1639-44. 6. Anupam Sachdeva, Dr SP Yadav, Dr NK Pati, Dr Bharat R Agrawal. Draft Guidelines for the management of Sickle Cell Disease in Children and Adolescents, for and on behalf of Pediatric Hematology Oncology (PHO) chapter of IAP, 2005. 7. Karlsson, S. The first steps on the gene therapy pathway to anti-sickling success. Nature Medicine 2000; 6: 139-40. 8. Lewis R. Human Genetics: Concepts and Applications, 3rd ed., 334-35, WCB/McGraw-Hill, Boston.

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Index A

B

Abscess 81 Achalasia cardia 94 Achondrogenesis 186 Achondroplasia 189 Acne neonatorum 53 Acrodermatitis enterohepatica 27 Acyclovir 6 Acute dystonic reaction 178 Adenoma sebaceum 154 Aganglionic megacolon, congenital 105 Agenesis of corpus callosum 173 Albendazole 12 Albers-Schonbergs syndrome 207 Albinism 196 Alopecia 16 Alopecia areata 18 Ambiguous genitalis 78 Amniotic band 58 Anagen effluvium 17 Anaphylactoid purpura 20 Anencephaly 171 Angelman syndrome 166 Anogenital wart 7 Anorectal malformation 108 Anus-Imperforate 108 Apert’s syndrome 203 Aplasia of depressor anguli oris muscle 57 Arachnodactyly Marfan syndrome 194 Ascaris lumbricoides 12 Asphyxiating thoracic dystrophy 188 Asymmetric crying facies 57 Ataxia telangiectasia 156 Atopic dermatitis 15 Autoimmune thyroiditis 76

Baby of diabetic mother 54 Balanoprosthitis 115 Bardet-Biedl syndrome 209 Barium enema, Intussusception 104 Beckwith-Weideman syndrome 56 Bells palsy 161 Birth trauma 62 Bitot spot 225 Bladder extrophy 123 Blepharophimosis syndrome 211 Brachydactyly 145 Breast abscess, neonate 50 Bullous impetigo 54

C Café au lait spots 152 Candidiasis oral 60 Caput succedaneum 49 Cataract 223 Cephalohematoma 48 CHARGE syndrome 202 Chickenpox (varicella) 4 Circumcision 116 Claustradium tetani 9 Clavicle fracture 62 Cleft lip 87 Cleft palate 87 Cliniodactyly 180 Club foot 143 Collodion baby 32 Coloboma 202 Collar-stud abscess 8 Condylomata accuminata 7 Congenital cataract 223 club foot 143 club hand 144 Hypertrophic pyloric stenosis 95

hypoplasia of depressor anguli oris muscle 57 hypothyroidism 74 diaphragmatic hernia 111 melonocytic nevus 40 ptosis 223 scoliosis 148 syphilis 60 twin 128 Cushing’s syndrome 73 Cutis laxa 35 Cutis marmorata 48 Cutis marmorata Telangiectatica congenita 25 Cutis Verticis Gyratus 157 Cystic hygroma 84 Cysticercosis 159

D Dermatofibroma 40 Dermatographism 39 Dermatitis atopic 15 seborrheic 22 Dermoid cyst 83 Diaphragmatic hernia 111 Digital abnormalities 144 Disorganization-like syndrome 204 Down syndrome 179 Drug reaction erythema multiforme major 18 erythema multiforme minor 18 Duodenal atresia 97 Duchenne muscular dystrophy 167

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242 Dysencephalia splanchnocystica 201 Dystonia, drug induce 178 Dystopia canthorum 159 Dwarf, achondroplasia 189

E Ear anomalies 69 Ebstein pearl 47 Ectodermal dysplasia 42 Ectopia vesicae 123 Ectrodactyly 146 EEC syndrome 146 Ectropion 32 Edwards syndrome 181 Empyema thoracic 132 Encephalocele 201 Endemic parotitis, see Mumps 3 Epibulbar dermoid 201 Epicanthic folds 179 Epidermolysis bullosa 26 Epignathus 67 Epispadias 123 Erb’s Duchenne palsy 63 Erythema multiforme major 18 Erythema toxicum 45 Eventeration of diaphragm 114 Exomphalus major 91 Extravasation injury 230 Extrophy of bladder 123

F Facial asymmetry 57 Facial nerve palsy 57 Facio-auriculo-vertebral syndrome 200 Fibroma, periungual 154 Fibular hemimelia 208 Fissured tongue 226 Flea bitten dermatitis 45 Foreign body aspiration 228 ingested 227 nose 227

Spotters in Pediatrics

G Gama benzene hydrochloride 30 Gastroschisis 92 Genetic counseling 215 Geographical tongue 226 Goldenhar syndrome 200 Greenstick fracture 147 Guttate psoriasis 31 Gynecomastia 71

H Hair cycle 16 Hairline, low in Turner syndrome 192 Hair tourniquet syndrome 117 Harlequin fetus 33 Head lice (see Pediculosis capitis) 30 Hemangioma 23 capillary 23 cavernous 23 Hemorrhagic disease of newborn 64 Henoch-Scholein purpura 20 Hernia Diaphragmatic hernia 111 inguinal 88 lumbar 90 umbilical 89 Herpes zoster 13 Hetrochromia 159 Hirschsprung’s disease 105 Human tetanus Immunoglobulin 10 Hurler’s syndrome 197 Hydatid disease 11 Hypomelanosis of Ito 43 Hypothyroidism 74 Hypoxic spells 220

I Icthyosis vulgaris 34 Idiopathic precocious puberty 72 Incision and drainage 82 Infantile hypertrophic pyloric stenosis 95 Inguinal hernia and hydrocele 88

Iniencephaly 172 Intraosseous transfusion 233 Intussusception 104 Ivermectin 30

J

Jeune syndrome 188 Joubert syndrome 175 Junctional nevus 47 Juvenile xanthogranuloma 42

K

Kabuki makeup syndrome 205 Kasabach-Merritt syndrome 24 Kawasaki disease 11 Klinefelter’s syndrome 78 Klippel-Trnaunay-Weber syndrome 158 Kocher-Debre-Semelaigne syndrome 75 Koplicks spot 1

L

Labial adhesion 116 Large head 172 Laser, vascular specific pulse dye 25 Lesch-Nyhan syndrome 205 Lissencephaly 174 Lobster Claw defect (see ectrodactyly) 146 Lop ear 69 Lumbar hernia 90 Lupus vulgaris 9

M

Macrocephaly (see large head) 172 Macrodystrophia lipomatosa 212 Majewski dysplasia 184 Malrotation 99 Marcus-Gunn phenomenon 162 Marfan’s syndrome 194 Mastitis neonatorum 50 Mayer-Rokitansky-KusterHauser syndrome 212 Measles 1

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Index Measles vaccine 3 Meckel Gruber syndrome 201 Meningoencephalitis 3 Microcephaly 172 Micropenis 77 Milia 47 Mili crystallina 52 Miliaria rubra 53 Milroy-heriditary lymphedema 211 MMR vaccine 3 Molluscum contageosum 6 Mongolian spot 46 Morquio’s syndrome 198 Multiple cartilaginous exostoses 147 Mumps 3 Myasthenia gravis 163

N

Necrotizing fasciitis 6 Neurocysticercosis 159 Neurocutaneous syndrome 150 Neurofibromatosis 151 Type I 151 Type II 152 Nevus congenital melonocytic 40 giant congenital pigment nevus 41 giant pigmented hairy nevus 41 junctional nevus 47 small congenital 41 Nevus of ITO 26 Nevus of OTA 25 Neonatal teeth 51 Neonatal hymenal tag 51 Neonatal vaginal bleed 51 Neural tube defect 168 spina bifida 168 meningomyelocele 169 sincepital meningoencephalocele 170 Nikolski sign 20 Noonan’s syndrome 193 Non immune hydrops 66 Nuchal skin thickening 192

O Ophthalmia neonatorum 68 Omphalocele 91 Osteogenesis imperfecta 141 Osteopetrosis 207 Oral thrush 60 Orchitis 3

P

Palatal perforation 229 Papular urticaria 38 Paraphimosis 116 Parasitic twinning 131 Parotitis, epidemic 3 Parotitis, recurrent 4 Parry-Romberg syndrome 157 Patau’s syndrome 182 Pediculosis capitis 30 Periorbital cellulitis 223 Periungual fibroma 154 Permethrine 29 Phenytoin-Induced Gingival Overgrowth (PIGO) 177 Phimosis 115 Pneumoperitoneum 102 Poland syndrome 206 Polydactyly 144 Portwine stain 23,24 Posterior urethral valve 121 Potter syndrome 207 Preauricular skin tag 69 Preauricular sinus 85 Precocious puberty 72 Prepucial pearl 47 Proboscis lateralis 208 Progeria 199 Psoriasis 31 Pyloric stenosis 93

R Rectal prolapse 110 Recurrent parotitis 4 Rett’s syndrome 164 Rhabdomyosarcoma 125 Rhinosporidiosis 224 Rickets 137 Ringworm infection 37 Robin anomalad 195 Rocker bottom foot 181

S Sacrococcygeal teratoma 68 Saldino-Noonan syndrome 183 Salmon patch 46 Scaphoid abdomen 112 Scabies 28 Sclera blue, Osteogenesis imperfecta 141 Scleroderma 36 Scrufuloderma 9 Scurvy 139 Seborrheic dermatitis 22 Short rib-polydactyly syndrome Type I 183 Type II 184 Sickle cell disease 234 Signs banana sign 170 cupola sign 103 gower sign 167 lemon sign 170 marfan’s sign 130 Molar tooth sign 175 Nikolski sign 20 Rigler’s sign 103 Steinberg sign 194 Whimberger sign 141 Whirlpool sign 101 Single umbilical artery 60 Split hand/foot deformity 146 Sternocleidomastoid tumour 52 Stevens-Johnson syndrome 18 Stibsons line 1 Sturge-Weber syndrome 155 Subacute sclerosing pan encephalitis 2 Subconjunctival dermoid 200 Supernumerary nipple 51 Syndactyly 145 Syphilis,congenital 60 Systemic sclerosis 36

T Taenia echinococcus 11 Tardive dystonia 178 Telogen effluvium 17 Tetanus 9 Tetanus neonatorum 10

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244 Tetrology of Fallot 220 Thanatophoric dysplasia 185 Thoracic dystrophy, asphyxiating 188 Thrush 60 Thyroglossal duct cyst 82 Tinea corporis 37 Tongue fissured 226 geographical 226 Toxic epidermal necrolysis 20 Trisomy 13 182 Trisomy 18 181

Spotters in Pediatrics Trisomy 21 179 Tubercular lymphadenopathy 8 Tuberous sclerosis 153 Turner’s syndrome 191 Twin to twin transfusion 65

U Urticaria 38 Umbilical hernia 89

V Varicella 4

Varicella vaccine 6 Varicella zooster immunoglobulin (VZIG) 7 Vater syndrome 210 Verruca vulgaris 7 Verruca plana 7 Vesicoureteral reflux 119 Vitamin A deficiency 225 Volvulus 101

W Waardenburg syndrome 159 Warts 7

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