Paediatric Genetics Flashcards
what are the face features associated with downs?
brachycephaly - small flatback head
flattened round face
upward slanting eyes
epicanthal folds
brushfield spots in iris
small, low set ears
protruding tongue
What is downs syndrome?
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
what are the most common cardiac complications of downs
in order of commonness:
endocardial cushion defect - AV septal canal defects
ventricula septal defect
atrial septal defect
tetrology of fallot
patent ductus arteriosus
what are the other features associated with downs
single palmar crease
hypotonia
congenital heart defects
duodenal atresia
hirschprung’s disease (aganglionic bowel = constipation)
Later complications of downs
sub/infertility
learning difficulties
short stature
repeated resp infection and glue ear
hypothyroidism
alzheimers
all
atlantoaxial instability
what antenatal screening done for downs
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
what antenatal testing is done for downs
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
what tests should be regularly done in downs, and name some mdt involved in their case
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
what are the trisomy disorders
trisomy 21 - downs
trisomy 18 - edwards
trisomy 13 - pataus
how do edwards and pataus present
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)
How do edwards and neural tube defects show on quadruple test
E: low hcg, oestriol, AFP
NTD: raised afp
What is Klinefelter syndrome?
male has additional x chromosome, becomes 47xxy instead of normal 46xy
extra x chromosomes ( 48xxxy etc) can occur - more severe features
chromosomal nondisjunction
how does klinefelter present
prognosis?
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
what is turners syndrome?
how does it present?
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
what conditions are associated with turners?
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)
What is fragile x syndrome
trinucleotide repeat disorder, affecting FMR1 (fragile x mental retardation 1) gene on x chromosome. (CCG)
affects boys much more severely than girls
presentation and diagnosis of fragile x
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
What is Noonan syndrome?
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
What is Prader Willi Syndrome?
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)
how does prader willi present?
hypotonia during infancy
constant hunger that leads to obesity
dysmorphic features
hypogonadism and infertility
short stature
how is prader willi managed?
growth hormone, aimed at improving muscle development and body comp
What is angelman syndrome?
deletion of maternal chromosome 15, or inheritance of both from father.
like prader willi but other way round
How does angelman syndrome present?
fascination with water
happy demeanour
widely spaced teeth
hand flapping
epilepsy
abnormal sleep patterns
dysmorphic features
What is William Syndrome and how does it present?
random microdeletion on chr 7
starbust eyes
wide mouth/big smile
small chin
elfin-like facies
very friendly and sociable
short stature
What is william syndrome associated with?
supravalvular aortic stenosis
adhd
htn
hypeercalcaemia - low calcium diet in mx)
What is Cystic Fibrosis?
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.
How does CF affect the pancreas and the lungs?
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.
Earliest presentation of CF in neonates?
Meconium ileus - Meconium isnt passed and instead causes a blockage in the intestine.
clinical features of CF
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
Ix of CF
Newborn guthrie heel prick screening (Immunoreactive trypsinogen)
GOLD: Chlorine sweat test. Pilocarpine induces sweating. Sweat has more chlorine (>60mmol/L)
Faecal elastase (pancreatic insufficiency)
cf Lifestyle advice
High calorie, high fat diet
No smoking
Regular exercise and physio
Flu vaccines
Resp mx of cf
Chest physio and exercise
Bronchodilator (Salbutamol)
Mucolytic (Dornose Alfa)
Nebulised Tobramycin if pseudomonas
Prophylactic flucloxacillin for life
digestive mx of cf and problems caused by it (5)
High calorie high fat diet
Fat soluble vitamins (ADEK)
Pancreatic enzyme replacement (Creon)
PPI - omeprazole
Ursodeoxycholic acid (make bile more soluble)
comps of cf + life expectancy
Life expectancy <40
CF related diabetes
Liver/biliary cirrhosis
Recurrent URTI
Malabsorption
- Delayed puberty
- Osteoporosis
- Infertility
What is duchenne muscular dystrophy and how does it present?
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
What do ix show in duchenne muscular dystrophy and what is its prognosis?
Raised CK
Genetic testing definitive
Prognosis
- Most cant walk by 12
- 25-30 yo life expectancy
- Associated with Dilated Cardiomyopathy
