Mrcpch Guide New Questions

MRCPCH GUIDE NEW QUESTIONS

Always: Invariably and without a single exception Never: Not in one single person nor on one single occasion Usually: In the majority of cases (at least 50% and strictly speaking, more than 50%). Other words with a similar meaning are: mostly, generally, commonly, mainly, predominantly and principally Probably: Something that is likely Possible/May/Can: Occurs in some instances Frequent/Often: Occurs regularly, is a regular occurence Rarely: Refers to something that is definitely unusual and uncommon. Other words with a similar meaning are: infrequently, occasionally Characteristic: A feature that occurs with sufficient frequency as to be of some diagnostic significance. Absence of the feature might make you doubt the diagnosis Typical: A feature that you would expect to be present (this is more or less the same as a characteristic feature) Recognised: A feature that has been reported and that is a fact that a candidate would reasonably be expected to know. Thus all characteristic features are recognised, but many recognised features could not be described as characteristic Associated: A feature which is well recognised but not necessarily common. A feature which occurs more frequently than by chance Pathognomonic: A feature which is found in that disorder and no other

SECTION 9: SYNDROMES MNEMONICS MRCP 1: Essentials ANGELMAN SYNDROME A Arms of a puppet N Never sleep G Gait ataxia E Epilepsy: characteristic EEG L Low IQ: severe mental retardation W Wide spaced teeth

O Orofacial abnormalities M Microcephaly A Amiable / Always laughing N No (or little) speech NOTES The mnemonic is changed from Angel ”man” to “woman” to remind you that the majority of these patients have deletions in their maternal chromosome 16q. Paternal (uniparental) disomy accounts for a smaller number of cases. Prader-Willi is the opposite, being caused by deletion of maternal chromosome 15q or paternal uniparental disomy). 1. Arm posture is characteristic: elbows and wrists in flexion. Creates look of a puppet* 2. Large mouth, magroglossia, wide spaced teeth. Also maxillary hypoplasia (creates prognathism; protruding mandible) 3. Lower IQ than those with Prader-Willli who have moderate mental retardation 4. Laughter is mostly inappropriate* * These 2 features lead to the phrase “happy puppet” which is used to describe people with this syndrome; they also clap hands a lot like a puppet. DI GEORGE’S SYNDROME C Cardiac abnormalities A Abnormal (dysmorphic) face T Thymic hypoplasia C Cleft palate H Hypocalcaemia 22 Chromosome 22 Predisposes to mental health problems i.e. Catch 22 situations are stressful and can lead to mental health problems! NOTES Aka “Velo-Cardio-Facial Syndrome”. Genetic cause of defective branchial arch (3rd and 4th pharyngeal pouches) development which then causes defective thymic development and the other abnormalities. The complete syndrome is listed above but partial forms exist. 1. Congenital malformations; esp interrupted aortic arch and truncus arteriosus 2. Characteristic facies are small low set ears, elongated face, almond-shaped eyes & wide nose. 3. Decreased T cells causes more infections (esp mucocutaneous candidiasis, PCP, myco

bacteria) and chronic diarrhoea. Bone marrow transplant can overcome this problem 4. Hypocalcaemia occurs due to decreased PTH – these patients fail to develop parathyroid glands. Often severe and leads to patients presenting with convulsions in neonatal period. 5. The defect on chromosome 22; this is a microdeletion on 22q11 which can be detected by Fluorescent In Situ Hybridisation (FISH) technique. 6. Psychiatric consequences are common, ranging from learning difficulties to OCD symptoms to presentations similar to schizophrenia or bipolar disorder. EDWARD’S SYNDROME E Eighteenth chromosome (trisomy): cause of syndrome! D Dorsiflexion of hallux occurs in all toes W Wedge-shaped base of skull: prominent occiput A Aortic & other cardiac abnormalities R Rockerbottom feet2 / Renal abnormalities are common D Diaphragmatic hernias / Dermatoglyphic abnormalities S Small nails & sternum Scissor hands: index and little fingers overlap the middle “Edward scissor hands” is a rather strange (yet critically acclaimed!) film with Jonny Depp, who plays a misunderstood man with scissors for hands! NOTES Other features are low set ears & micrognathia. Aplasia of radius, facial clefts and exomphalos can each occur in 20% of cases. Dislocation of hips is common. Patients are born of low birthweight (IUGR) and with hypotonia. 50% of cases die before 2 months (99% before 10 years). Profound mental retardation manifests itself if patient lives long enough. 1. Increased incidence of VSD & PDA 2. “Rockerbottom feet”: vertical talus causes convex foot with prominent heel 3. Renal abnormalities: horseshoe kidney and hydronephrosis 4. Increased number of arch patterns FETAL ALCOHOL SYNDROME F Facies A ADHD

C Cardiac abnormalities I Intestinal abnormalities (esp hernias) A Auditory abnormalities L Low IQ & birthweight NOTES 1. Microcephaly, midface hypoplasia, flattened philtrum, thin upper lip, cleft palate, jaw abnormalities (retrognathia in infancy then micrognathia or relative prognathism in adolescence), low nasal bridge, small widely spaced eyes, strabismus, ptosis, short palpebral fissures, posterior rotation of the ears. 2. ADHD = Attention Deficit Hyperactivity Disorder. Also many other cognitive & behavioural problems 3. Most common congenital problems: ASD/VSD, Fallot’s, PDA, great vessel abnormalities & dextrocardia NB: Alcohol in pregnancy causes widespread damage and affects most tissues; urogenital, renal, musculoskeletal & ocular abnormalities also common

HOMOCYSTINURIA v MARFAN’S (DIFFERENCES) Homocystinuria has the following features (that Marfan’s doesn’t): High: Thromboembolism (DVT/PE) Heart complications Epilepsy Low: Bone density(i.e. osteoporosis) Lens IQ Numbers in pedigrees Detached retina The blind reminds you of the eye complications and the fact that it is underneath the word “the” reminds you it is the cause of things being lowered! NOTES Otherwise these 2 syndromes look similar, with the same body habitus & skeletal features. 1. IHD, aortic regurgitation (& dissection) or mitral prolapse 2. Dislocation is down (and in): in Marfan’s it is up (and out) 3. Autosomal recessive inheritance; Marfan’s = Autosomal dominant 4. Detached retina is the only one in this list that doesn’t fit with the list that it is in – it is of increased frequency in Homocystinuria!

HURLER’S (& HUNTER’S*) SYNDROME T Thrills (heart murmurs) H Hepatosplenomegaly I Increased head : body ratio2 C Corneal Clouding + papilloedema K Kyphosis Bones Increased diamm of bones (“Stocky”!) Thick bones are a feature of the illness and thick also refers (in a politically incorrect way) to the low IQ seen in this syndrome; developmental delay also seen before this. NOTES 1. Thickened valves (also heart failure, myocardial rigidity & narrowing of arteries) 2. Large head with frontal bossing 3. Differentiates this condition from Hunter’s syndrome* Hurler’s syndrome is genetic (autosomal recessive) disorder of mucopolysaccharide metabolism (lysosomal storage). Other features: protruberant abdomen, umbilical hernias, short stature (“dwarfism”) & generally “coarse” facial features (hence old name “Gargoylism”) *Hunter’s syndrome: X recessive mucopolysaccharidosis with almost identical features apart from: 1. No corneal clouding 2. Have nodes over the scapulae. PHENYLKETONURIA “Dumb Blonde”: Dumb: Mental retardation Blonde: Blonde hair Blue eyes Pale skin (hypopigmentation) NOTES Other features: Irritable (mood) + Itchy (eczema) Genetics:mutations of phenylalanine hydroxylase gene on chromosome 12, that normally converts phenylalanine into tyrosine, causing excess phenylalanine. Diagnosis is by Guthrie (heel prick) test.

PRADER-WILLI SYNDROME P Palpebral fissure abnormality (“almond shape”) R Round face /obese A Angry outbursts D Downturned mouth E Eat excessively R Reduced tone Willy small genitals / cryptorchidism NOTES Willy also makes you remember the deletion is of the paternal chromosome (15q). Maternal (uniparental) disomy accounts for a smaller number of cases. Angelman is the opposite, being caused by deletion of maternal chromosome 15q or paternal uniparental disomy). 1. Stubborness/rages. Also learning difficulties (moderate to severe) & verbal perseverance (stick to favourite topics!) 2. Overwhelming compulsion to eat (hyperphagia) 3. Also small hands / feet & small in general (ie height!)

There is a rostral–caudal progression of signs seen with both lateral and central transtentorial herniation, indicating worsening of the herniation. This begins with diencephalic involvement followed by mesencephalic, pontine, and finally medullary involvement. The signs described above are seen with involvement of the mid-brain and upper pons. With herniation at the level of the reticular formation there is altered consciousness. With involvement of the diencephalon there is drowsiness or agitation with Cheyne–Stokes respirations. Pupils are small but brisk. Eye movements can be roving, the vestibulo-ocular reflex is weak or brisk. There is loss of vertical movement. Decorticate posturing to stimuli occurs. Plantars are extensor. With involvement of the low pons– upper medulla the patient will be in a coma with tachypnoea. Small mid-position fixed pupils are present. Vestibulo-ocular reflex is absent. There is flaccid flexor response to noxious stimuli. With involvement of the medulla the patient will be in coma. Breathing will become apnoeic, then stop. Pupils are fixed and dilated. There is no vestibulo-ocular reflex. Limbs are flaccid with no deep tendon reflexes.

Treatment algorithm for children by first medical responders:

In addition, for all severe or recurrent reactions and patients with asthma, give hydrocortisone: >12 years: 100–500 mg intramuscularly 6–12 years: 100 mg intramuscularly 1–6 years: 50 mg intramuscularly The alternative route for hydrocortisone is slowly via the intravenous route. If the clinical manifestations of shock do not respond to drug treatment, give 20 ml/kg body weight of intravenous fluids. A rapid infusion or one repeat dose may be necessary.

An inhaled ß2-agonist such as salbutamol may be used as an adjunctive measure if bronchospasm is severe and does not respond rapidly to other treatment. For profound shock judged IMMEDIATELY LIFE-THREATENING, give cardiopulmonary resuscitation/advanced life support if necessary. Consider a slow intravenous infusion of epinephrine 1:10 000 solution. This is HAZARDOUS and is recommended only for the experienced practitioner who can also obtain intravenous access without delay. Note the different strength of epinephrine that may be required for intravenous use. Acne affects 90% of teenagers and 25% of infants. Boys are more commonly affected than girls and acne persists beyond the age of 25 in 15%. Acne is usually associated with normal levels of testosterone. Causes include medication (e.g. oral contraceptive pill, steroids, phenytoin), irritants (e.g. cosmetics), occlusion (e.g. friction by head bands), emotional stress, menstruation and endocrine abnormalities (e.g. Cushing syndrome, diabetes, virilising tumour, polycystic ovaries). Propionibacterium acnes is an anaerobic diphtheroid and this, together with yeast, colonises the blocked sebaceous glands and breaks down the sebum, releasing free fatty acids that cause an inflammatory reaction in the dermis. Secondary infection of the papules causes pustules, cysts and scars. In moderate cases, the treatment with erythromycin should continue for at least 6–12 months because its maximum effect is not achieved before 3–6 months. Even so, it may still relapse requiring a further 3 months of treatment, so the patient must be well motivated. Severe cases (multiple cysts, pits, scars and keloids) and resistant moderate cases should be referred to the dermatologist. Roaccutane should only be prescribed by the hospital specialist. LFTs and lipids should be checked before starting treatment and monitored throughout. Roaccutane causes dry skin and mucosa and is 100% teratogenic (therefore oral contraception should be continued for at least one month after cessation of treatment). The kidney, specifically the peritubular complex of the kidney, is the predominant site of erythropoietin production and not endothelial cells. Vitamin B6 and not vitamin C is a coenzyme in the initial stage of haem synthesis. The mitochondria produce haem while ribosomes produce the globin chains. A molecule of haemoglobin is composed of four globin chains attached to their own haem moiety and the red cell does metabolize glucose only.

Fresh frozen plasma (FFP) results from centrifuging out the cellular components of blood and therefore FFP will contain all of the coagulation factors and complement. Cryoprecipitate is collected following a controlled thaw of FFP and contains fibrinogen and factor VIII, as well as von Willebrand factor and factor XIII. As FFP and platelets may contain isohaemagglutinins, these two blood product transfusions should be ABO-compatible with the recipient. 1 unit of random donor platelets per 10 kg of patient bodyweight normally raises the platelet count in the region of 30–60 × 109/L. The recommended volume for an FFP infusion is 10 ml/kg. Sodium channelopathies include the autosomal dominant conditions hyperkalaemic periodic paralysis and paramyotonia congenita. Potassium channelopathies include Andersen syndrome

(dysmorphism, ventricular arrhythmia and periodic paralysis). Chloride and calcium channel disorders are also well described.     

Brush teeth with help: by 26 months Play ball with examiner: by 17 months Wave bye-bye: by 15 months Put on a T-shirt unaided: by 3 years Play ‘pat-a-cake’: by 11 months

Many drugs such as phenytoin, penicillin, clonidine, methyldopa, beta-blockers and sulfonamides may induce SLE. Proximal renal tubular acidosis can be part of Fanconi syndrome, of which there are a number of causes: cystinosis; tyrosinaemia; galactosaemia; Lowe syndrome; Wilson’s disease; heavy metal poisoning; idiopathic.

The sites of absorption are: duodenum and jejunum (fluids, carbohydrates, proteins, fat, iron, calcium, zinc, folate and most vitamins); terminal ileum (vitamin B12, bile salts, vitamin K and vitamin C); colon (water, sodium and fermented carbohydrates). Definition is excess body fat, and the body mass index (BMI) should be measured and plotted on an age appropriate chart (overweight > 91st centile; obesity > 98th centile). Most children suffer from simple obesity (99%), that is with no underlying physical cause, and this is the most important part of the initial assessment.

Osteomyelitis 3–10 years is more common in boys than in girls and there may be a history of trauma. The most commonly involved organism is Staphylococcus aureus and treatment should be intravenous flucloxacillin (plus fusidic acid). Other causes are Streptococcus pneumoniae or possibly Escherichia coli. In infants under 2 years of age alternative organisms include Group B streptococcus and Haemophilus influenzae type B. In patients with sickle cell disease, Salmonella and Gramnegative infections should be considered. Treatment may require surgical debridement and antibiotics should be given for 6 weeks.

UTIs are more common in boys in the first month of life and become more common in girls from about 6 months. E. coli is responsible for approximately 80% of cases. Other causative organisms include Klebsiella spp., Streptomyces albus and Proteus spp. In neonates most UTIs are haematogenous in origin, whereas in older infants and children infection generally ascends from the native bowel flora. About 35% of all children presenting with a UTI have VUR, with 45% of these having some structural or functional abnormality of their urinary tract (90% if < 2 years and 60% if < 5 years). The diagnosis of VUR is most important in the under-2s because this is the age group most likely to develop reflux nephropathy. In older age groups, there is a move away from investigating for VUR because the clinical sequelae are less clear cut. Significant bacteriuria from a normal mid-stream urine (MSU) or clean catch has > 105 CFU of bacteria/mL; however, a suprapubic aspirate requires > 103 CFU/mL only.

Tuberous sclerosis – autosomal dominant, 1 in 50,000:    

‘Ash leaf’ macules (from infancy): depigmented lesions approximately 1–2 cm long ‘Shagreen’ patches (from 2 years): areas of roughened skin, usually sacral, likened to shark skin Adenoma sebaceum (from 5 years): 1- to 2-mm papules, usually facial (butterfly distribution) Epilepsy (usually before 2 years)

Neurofibromatosis type 1 – autosomal dominant, 1 in 2,500:    

Café-au-lait spots (> 2 in children under 5 years, > 5 in children over 5 years is significant) Axillary freckling Neurofibromata (from 12 years): papules anywhere on the body Epilepsy only in 10%

Ataxia telangiectasia – autosomal recessive, a chromosomal repair defect. Affected children present as late walkers. Ataxia develops in early childhood and is progressive: 

Conjunctival telangiectasia: develops from 5 years

Incontinentia pigmenti: X-linked dominant.    

Vesicular stage: neonatal period, linear distribution; resolves by 1 month Verrucose stage: 1–4 months, warty lesions appearing mainly on limbs; resolves by 6 months Whorl stage: by 2 years, linear and whorl pattern of hyperpigmentation on limbs Epilepsy in over 30%

Sturge–Weber syndrome – sporadic, 1 in 50,000:   

Naevus in trigeminal distribution with an ipsilateral leptomeningeal haemangioma Intracranial calcification is common, especially in the occipital region Seizures develop in early childhood

Peroxisomes are present in all cells except mature red cells. They have many synthetic and catabolic functions. They are the site of biosynthesis of plasmalogens, bile acids, and cholesterol. They are the site of ß-oxidation of very long chain and branched chain fatty acids. Other oxidative processes include those of phytanate (vitamin A), glutaric acid, and pipecolic acid. They are also the site for glyoxylate metabolism. Peroxisomal disorders may result from a complete absence of function (Zellweger syndrome), from loss of a few processes, or from blockage of a single pathway, such as phytanate in Refsum disease, and VLCFA oxidation in adrenoleukodystrophy. The urea cycle occurs in the cytoplasm and mitochondrion, and glycosylation of glycoproteins occurs in the endoplasmic reticulum and Golgi. Disorders of this pathway lead to the congenital disorders of glycosylation (CDG).

Rasmussen’s encephalitis typically presents with focal seizures which can be frequent or even continuous. Rasmussen described a syndrome of seizures, spastic paralysis and learning difficulties associated with chronic encephalitis. The brain imaging can be normal early in the disease. Later in the course, cerebral swelling can be seen with high intensity lesions in the basal ganglia and periventricular white matter on T2-weighted imaging. The diagnosis would need to be confirmed on brain biopsy in a clinically suspected case.

Hallervorden–Spatz is a rare degenerative disorder inherited as a recessive trait. There is usually progressive dystonia, rigidity and choreoathetosis. Death usually occurs by early adulthood. Imaging shows lesions of the globus pallidus. Neuropathology reveals excess accumulation or iron-containing pigments in the globus pallidus and substantia nigra. Segawa disease is otherwise known as dopa-responsive dystonia due to the clinical response. It is more common in females and typically presents around the age of 6 years with dystonic posturing of the lower limb. It improves with a small dose of levodopa.

Friedreich’s ataxia is the most common hereditary ataxia. The triplet repeat GAA is located in the first intron of the frataxin gene on chromosome 9q13. The frataxin protein is a mitochondrial protein that plays a part in iron homeostasis. Onset usually occurs around puberty with clumsiness of gait. Clinical features are: autosomal recessive onset prior to age 25 years, progressive limb and gait ataxia, absent tendon reflexes in the lower limbs, and evidence of axonal and sensory neuropathy on electrophysiological investigation. The motor nerve conduction velocities are usually normal. There is progression to dysarthria, areflexia, and loss of proprioception of distal joints, extensor plantars, and pyramidal weakness of the legs.

Behçet’s disease is most commonly associated with posterior uveitis, although hypopyon can also be seen. The other typical pairings should be juvenile idiopathic arthritis with scleritis, seronegative arthropathies with anterior uveitis, SLE with retinal vasculits and sarcoid with uveitis. Hyper-IgD is associated with attacks of fever every 4–8 weeks, with each attack lasting 3–7 days. Other symptoms and/or signs include abdominal pain, diarrhoea, vomiting, lymphadenopathy, arthralgia or arthritis and skin lesions. IgD levels range from 145 to 5300 U/ml (normal levels are < 100 U/ml).