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 GEORGES 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.

EDWARDS 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, Fallots, 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 MARFANS (DIFFERENCES)
Homocystinuria has the following features (that Marfans doesnt):
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 Marfans it is up (and out)
3. Autosomal recessive inheritance; Marfans = Autosomal dominant
4. Detached retina is the only one in this list that doesnt fit with the list that it is in it is
of increased frequency in Homocystinuria!

HURLERS (& HUNTERS*) 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 Hunters syndrome*
Hurlers 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)
*Hunters 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 rostralcaudal 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 CheyneStokes 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: 100500 mg intramuscularly
612 years: 100 mg intramuscularly
16 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
2
-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 612 months
because its maximum effect is not achieved before 36 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 B
6
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 3060 10
9
/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; Wilsons 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 B
12
, 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 310 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 Gram-
negative 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 12 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:
Caf-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: 14 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%
SturgeWeber 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 -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).
Rasmussens 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.

HallervordenSpatz 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.

Friedreichs 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.
Behets 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 48 weeks, with each attack lasting 37 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).