Genetics

Question 1

cardiac abnormalities assoc. with Down syndrome?

Answer 1

atrioventricular septal defect-deficiency of atrioventricular septum, most common congenital heart defect in downs
VSD
tetralogy of Fallot
isolated persistent PDA

Question 2

cardiac abnormalities assoc. with Turner syndrome?

Answer 2

coarctation of aorta

aortic valve stenosis

Question 3

cardiac abnormalities assoc. with Noonan syndrome?

Answer 3

hypertrophic cardiomyopathy
ASD
pulmonary valve stenosis

Question 4

what is an antrioventricular septal defect, and in which condition is this most commonly assoc. with?

Answer 4

Down syndrome-15-20% of pts,and responsible for 35-40% of congenital heart disease cases in Downs patients

defect: failure to form part of heart which develops from the endocardial cushions: lower part of atrial septum and ventricular septum just below AV valves, and cushions responsible for completing separation of mitral and tricuspid valves from a single valve. any or all of these may be involved.

Question 5

how common is congenital heart disease in Down syndrome?

Answer 5

40% of patients

Question 6

symptoms of an atrioventricular septal defect?

Answer 6

increased work of breathing-breathing harder and tachypnoea
sweat and/or tire out whilst feeding
slow growth or even weight loss

with complete defect, present with cyanosis and birth or heart failure at 2-3wks of life

Question 7

common ECG feature of AV septal defect?

Answer 7

superior axis deviation (L axis deviation)-tallest R wave aVL-LV overload with mitral insufficiency and anomaly in AV conduction

Question 8

most common genetic cause of severe learning difficulties?

Answer 8

Down syndrome

Question 9

facial features of Downs?

Answer 9

flat occiput (brachycephaly) and ‘3rd fontanelle’-result of open suture*
upslanted palpebral fissures
epicanthic folds-fold of skin running across inner edge of palpebral fissure
brushfield spots in iris-little white spots
cataracts
small low set ears, can be stenotic meatus
round face and flat nasal bridge
small mouth and protruding tongue
high arched palate

Question 10

clinical features on inspecting child with Downs, other than facial features?

Answer 10

hypotonia-arms and legs extended rather than flexing
single palmar crease (Simian crease) as small palms
incurved 5th finger towards ring finger (clinodactyly)
pronounced ‘sandal’ gap between big and second toe
short neck
hyperflexibility

Question 11

RFs for having a baby with Downs?

Answer 11

maternal age-1/30 risk if age 45 yrs
FH
previously affected pregnancy

Question 12

how might an extra chromosome 21 in Downs arise?

Answer 12

trisomy 21-meiotic non-disjunction -pair of chromosme 21s fail to separate so 1 gamete has 2 chromosome 21s (usually egg*), so gamete fertilisation forms zygote with trisomy 21, incidence related to maternal age.
translocation-extra chromosome joined onto another 1 (usually 14, can be 15, 21 or 22)=Robertsonian. 1 parent may carry a balanced translocation.
mosaicism-some cells have normal pair of chromosome 21s, some have 3 (trisomy), usually result on non-disjunction at mitosis after formation of chromosomally normal zygote, but can arise by later mitotic non-disjunction in trisomy 21 conception. Downs phenotype may be milder.

Question 13

antenatal screening for downs?

Answer 13

all pregnant women offered screening tests measuring biochemical markers in blood samples-free beta-hCG and pregnancy assoc. plasma protein A-PAPP-A-reduced, and nuchal thickening on US
if books later in pregnancy, can do less accurate quadruple test-beta-hCG-raised, alpha-fetoprotein-reduced, inhibin-A-raised and unconjugated estriol-reduced, from 14+2 to 20+0 wks gestation.
+ve screening test if risk mum carrying downs baby is 1 in 150.
if increased risk of Downs in fetus identified then amniocentesis offered to check fetal karyotype if more than 15 wks gestation, chorionic villus sampling if less than 13 wks gestation. both carry increased miscarriage risk, doubled risk with chorionic villus sampling.

Question 14

cardiac complications that may develop in adult patient with downs and without known congenital heart disease?

Answer 14

mitral valve prolapse

aortic regurge

Question 15

Opthalmic and ENT complications in patients with Downs?

Answer 15

hearing loss-conductive, SN or mixed, should be assessed at annual r/v and should have auditory evoked potential testing before 6mnths of age.
otitis media
sinusitis
pharyngitis
OSA
cataracts
congenital glaucoma
refractive error
strabismus
keratoconus
nystagmus

Question 16

GI disorders assoc. with downs?

Answer 16

duodenal atresia
oesophageal atresia or tracheo-oesophageal fistula
pyloric stenosis
meckel’s diverticulum
hirschsprung’s disease (most common GI complaint)-congenital aganglionic megacolon with absence of PNS ganglion cells in rectum ascending proximally and proximal dilated bowel
imperforate anus
GOR
dental problems-delayed and unusual eruption patterns, missing teeth
coeliac disease-should consider screening blood tests-anti-TTG IgA and total IgA 1st choice.

Question 17

orthopaedic disorders assoc. with Downs?

Answer 17

atlanto-axial instability (also assoc. with AS)-neck pain, limited movements or symptoms/signs suggestive of cord compression, may be bladder problems, gait abnormalities or clumsiness
hyperflexibility
scoliosis
hip dislocation after 2 yrs (so note not picked up on neonatal ortolani and barlow tests)
patellar subluxation or dislocation
foot deformities

Question 18

endocrine disorders assoc. with down’s?

Answer 18

hypothyroidism-need annual TFTs

Question 19

neurological and pscyhiatric associations of down’s syndrome?

Answer 19

learning difficulties
behavioural problems
delayed motor milestones
epilepsy and seizures
early onset Alzheimer's-due to increase in beta amyloid protein assoc. with trisomy 21

Question 20

haematological complications assoc. with down’s?

Answer 20

acute myeloblastic leukaemia
acute lymphoblastic leukaemia-most common Ca of childhood
acute megakaryoblastic leukaemia
polycythameia and transient myeloproliferative disorder-self-limiting type of leukaemia which regresses spontaneously by 2mnths, may occur in newborns. *leukomoid reaction-transient reactive increase in WCC, can mimic leukaemia.
increased infection risk e.g. pneumonia due to impaired cellular immunity.

Question 21

characteristic features of DiGeorge syndrome?

Answer 21

CATCH22-deletion on chromosome 22
congenital heart defects e.g. tetralogy of fallot
abnormal facies-hypertelorism, hooded eyelids, tubular nose, broad nose tip, small mouth, abnormal ears
thymus hypoplasia-low T cell numbers, immunodeficiency
cleft lip and palate
hypoparathyroidism-hypocalcaemia

feeding and swallowing difficulties-poor pharyngeal muscle coordination, GOR, dysphagia-silent aspiration and pneumonia, cardiac problems-SOB-difficulty feeding and faltering growth.
hearing loss
speech difficulties and developmental delay
behavioural and psychiatric problems e.g. ASD, ADHD

Question 22

differential diagnosis for DiGeorge syndrome?

Answer 22

CHARGE syndrome:
coloboma
heart anomaly
atresia-choanal-back of nasal passage is blocked due to failure of nasal fossae to recanalize during fetal development
retardation-developmental and growth
genital anomaly
ear anomaly

Question 23

Characteristic neurological manifestation of trisomy 21?

Answer 23

Hypotonia

Question 24

clinical features of edward’s syndrome (trisomy 18)?

Answer 24

low birthweight
prominent occiput
small mouth and chin
flexed, overlapping fingers
short sternum
'rocker-bottom' feet
cardiac and renal malformations

Question 25

clinical features of patau syndrome (trisomy 13)?

Answer 25

structural defect of brain
scalp defects
microphthalmia and other eye defects
cleft lip and palate
polydactyly
cardiac and renal malformations

Question 26

clinical features of Turner syndrome (45, X)?

Answer 26

short stature
lymphoedema of hands and feet in neonate, which may persist
low set ears
webbed neck/thick neck
shield like chest
widely spaced nipples
delayed puberty
infertility-ovarian dysgenesis-ovaries appear as 'streaks'
congenital heart defects, espec. coarctation of aorta
hypothyroidism
renal anomalies
pigmented moles
recurrent otitis media
normal intellectual function in most

Question 27

treatment for Turner syndrome?

Answer 27

GH therapy
oestrogen replacement for development of secondary sexual characteristics at time of puberty, but infertility persists-however, may be able to get pregnant with use of IVF with oocyte donation.