Paediatric Genetics

Question 1

what are the face features associated with downs?

Answer 1

brachycephaly - small flatback head

flattened round face

upward slanting eyes

epicanthal folds

brushfield spots in iris

small, low set ears

protruding tongue

Question 1

What is downs syndrome?

Answer 1

trisomy 21 (3 copies) causing characteristic physical features eg flattened facial profile, upward slanted eyes, single palm crease.

intellectual disability
developmental delayed
increased risk of certain conditions

Question 2

what are the most common cardiac complications of downs

Answer 2

in order of commonness:

endocardial cushion defect - AV septal canal defects

ventricula septal defect

atrial septal defect

tetrology of fallot

patent ductus arteriosus

Question 3

what are the other features associated with downs

Answer 3

single palmar crease

hypotonia

congenital heart defects

duodenal atresia

hirschprung’s disease (aganglionic bowel = constipation)

Question 4

Later complications of downs

Answer 4

sub/infertility

learning difficulties

short stature

repeated resp infection and glue ear

hypothyroidism

alzheimers

all

atlantoaxial instability

Question 5

what antenatal screening done for downs

Answer 5

best: combined test - 11-14 weeks

• uss measures nuchal thickness - back of fetal neck - over6 mm significant.
• bhcg - higher= greater risk

-papp-a : pregnancy associated plasma protein a - lower result = greater risk

triple and quadruple tests also done if booked later (14-20 weeks)

T: bhcg, afp (lower=risk) and serum oestriol (lower=risk)
Q: adds inhibin A (higher=risk)

all bloods are maternal

Question 6

what antenatal testing is done for downs

Answer 6

if higher risk (over 1 in 150) , either second screening or diagnostic test.

NIPT - second screening but non invasive. analysis cell free fetal dna (cffdna) in maternal blood. 99% sensitivity and specficity

diagnostic testS:
- chorionic villus sampling - uss guided biopsy of placental tissue (under 15 weeks)

amniocentesis - later in pregnancy, when enough amniotic fluid to take safe sample

Question 7

what tests should be regularly done in downs, and name some mdt involved in their case

Answer 7

thyroid - 2 yearly
echocardiogram
regular audiometry and eye checks

OT
speech and language therapy
physio
dietician
paediatrician
gp
health visitors
caridologist for congenital heart disease
ent specialist for ear problems
audiologist for hearing aids
optician for glasses
social services for social care and benefits
additional support with educational needs

Question 8

what are the trisomy disorders

Answer 8

trisomy 21 - downs
trisomy 18 - edwards
trisomy 13 - pataus

Question 9

how do edwards and pataus present

Answer 9

pataus:
-microcephalic, small eyes
-cleft lip/palate
-polydactyly
- scalp lesions

edwards:
- micognathia - small lower jaw
- low-set ears
-overlapping of fingers
-rocker bottom feet (convex foot bottom - present in both)

Question 10

How do edwards and neural tube defects show on quadruple test

Answer 10

E: low hcg, oestriol, AFP

NTD: raised afp

Question 11

What is Klinefelter syndrome?

Answer 11

male has additional x chromosome, becomes 47xxy instead of normal 46xy

extra x chromosomes ( 48xxxy etc) can occur - more severe features

chromosomal nondisjunction

Question 12

how does klinefelter present

prognosis?

Answer 12

develop as normal until puberty then develop features

taller
wider hips
gynaecomastia
weak muscles, small testicles, reduced libido
shyness
infertility
low test but high gonadotrophin

life expectancy: close to normal. slight increase of:
- breast cancer (still less than f )
- osteoporosis
-diabetes
-anxiety/depression

Question 13

what is turners syndrome?

how does it present?

Answer 13

female has single x chromsome making them 45XO. (o refers to empty space) - caused by either presence of only 1 x or deletion of short arm of one.

short stature, webbed neck, widely spaced nipples

cubitus valgus - when arm is extended down with palm facing out, angle of forearm is exaggerated)

underdeveloped ovaries with reduced function (infertile)

late/incomplete puberty

primary amennorhoea

lymphoedema in neonates (feet)

horseshoe kidney

bicuspid aortic valve causing ejection systolic murmur

Question 14

what conditions are associated with turners?

Answer 14

recurrent otitis media and uti

coarctation of aorta and bicuspid valve, causing ejection systolic murmur

hypothyroid

obesity,dm,htn,osteoporosis
learning diabilities
autoimmune (thyroid, chrons)

Question 15

What is fragile x syndrome

Answer 15

trinucleotide repeat disorder, affecting FMR1 (fragile x mental retardation 1) gene on x chromosome. (CCG)

affects boys much more severely than girls

Question 16

presentation and diagnosis of fragile x

Answer 16

learning difficulties

large low set ears, long narrow face, high arched palate

macroorchidism

hypotonia
autism
mitral valve prolapse
antenatal by chorionic villus sample or amniocentesis

analysis of ccg repeats using restriction endonuclease digestion and souther blot analysis

Question 17

What is Noonan syndrome?

Answer 17

autosomal dominant condition (c12 maybe?) - “male turners”

webbed neck, widely spaced nipples, short stature, pectus carinatum and excavatum

ptosis
triangular face
lowset ears
factor XI deficiency and pulmonary valve stenosis

Question 18

What is Prader Willi Syndrome?

Answer 18

loss functional genes on proximal arm of chromsome 15.

can be due to deletion of chromosome or when both are inherited by moth.

called angelman syndrome if deletion is from morth (or both inherited by father)

Question 19

how does prader willi present?

Answer 19

hypotonia during infancy

constant hunger that leads to obesity

dysmorphic features

hypogonadism and infertility

short stature

Question 20

how is prader willi managed?

Answer 20

growth hormone, aimed at improving muscle development and body comp

Question 21

What is angelman syndrome?

Answer 21

deletion of maternal chromosome 15, or inheritance of both from father.

like prader willi but other way round

Question 22

How does angelman syndrome present?

Answer 22

fascination with water

happy demeanour

widely spaced teeth

hand flapping

epilepsy

abnormal sleep patterns

dysmorphic features

Question 23

What is William Syndrome and how does it present?

Answer 23

random microdeletion on chr 7

starbust eyes

wide mouth/big smile

small chin
elfin-like facies
very friendly and sociable
short stature

Question 24

What is william syndrome associated with?

Answer 24

supravalvular aortic stenosis

adhd
htn
hypeercalcaemia - low calcium diet in mx)

Question 25

What is Cystic Fibrosis?

Answer 25

A phenylalanine deletion on the CFTR (CF transmembrane conductance regulator) gene on chromosome 7, causing secretions to become much thicker. Mainly affects pancreas and lungs.

Autosomal recessive.

Question 26

How does CF affect the pancreas and the lungs?

Answer 26

Pancreas - thick pancreatic and biliary secretions block ducts, causing pancreatitis (autodigestion), cholangitis and lack of digestive enzymes in GI tract.

Causes failure to thrive, steatorrhoea and endocrine dysfunction e.g. CF diabetes.

Lungs - Impaired mucociliary clearance. Causes an obstructive pattern and thick immobile secretions = repeat S aureus and P aeruginosa infections.

Question 27

Earliest presentation of CF in neonates?

Answer 27

Meconium ileus - Meconium isnt passed and instead causes a blockage in the intestine.

Question 28

clinical features of CF

Answer 28

Meconium ileus
Chronic cough, wheeze and recurrent infections (S aureus, P aeruginosa and H influenza)
Nasal polyps and sinusitis
Pancreatic insufficiency (steatorrhoea, malabsorption)
GORD
Clubbing

Question 29

Ix of CF

Answer 29

Newborn guthrie heel prick screening (Immunoreactive trypsinogen)
GOLD: Chlorine sweat test. Pilocarpine induces sweating. Sweat has more chlorine (>60mmol/L)
Faecal elastase (pancreatic insufficiency)

Question 30

cf Lifestyle advice

Answer 30

High calorie, high fat diet
No smoking
Regular exercise and physio
Flu vaccines

Question 31

Resp mx of cf

Answer 31

Chest physio and exercise
Bronchodilator (Salbutamol)
Mucolytic (Dornose Alfa)
Nebulised Tobramycin if pseudomonas
Prophylactic flucloxacillin for life

Question 32

digestive mx of cf and problems caused by it (5)

Answer 32

High calorie high fat diet
Fat soluble vitamins (ADEK)
Pancreatic enzyme replacement (Creon)
PPI - omeprazole
Ursodeoxycholic acid (make bile more soluble)

Question 33

comps of cf + life expectancy

Answer 33

Life expectancy <40
CF related diabetes
Liver/biliary cirrhosis
Recurrent URTI
Malabsorption
- Delayed puberty
- Osteoporosis
- Infertility

Question 34

What is duchenne muscular dystrophy and how does it present?

Answer 34

X linked recessive inherited disorder or dystrophin genes required for normal muscle function.

Progressive proximal muscle weakness from 5 years.
Calf pseudohypertrophy
Gower’s sign: Child uses arms to stand up from squat position

Question 35

What do ix show in duchenne muscular dystrophy and what is its prognosis?

Answer 35

Raised CK
Genetic testing definitive
Prognosis
- Most cant walk by 12
- 25-30 yo life expectancy
- Associated with Dilated Cardiomyopathy