Genetics

Question 1

What are the hallmark features of BWS and which are the most common prenatally?

Answer 1

Hallmark:
Omphalocele
Macrosomnia
Macroglossia

Most common observed PRENATALLY:
Macrosomnia (90%)
Polyhydramnios (50%)

Question 2

What is the genetic defect in BWS?

Answer 2

(Mainly) deregulation of imprinted genes within chromosome 11p15.5

Question 3

What are the surveillance recommendations in BWS?

Answer 3

Tumour surveillance every 3 months to age 8

1. Abdominal USS every 3 months to age 4
2. Renal USS (incl. adrenals) every 3 months between ages 4-8
3. Serum AFP every 2-3 months up to age 4

This is because risk of neoplasia concentrated in first 8 years of life

Question 4

What are the two most common neoplasias seen in BWS?

Answer 4

Wilm’s tumour

Hepatoblastoma

Question 5

What is the cause of hypoglycaemia in BWS?

Answer 5

Hyperinsulinaemia

Question 6

What are the clinical manifestations of Marfan syndrome?

Answer 6

Cardinal = Skeletal, cardiovascular, ocular

SKELETAL
Reduced upper:lower segment ratio, arm:height ratio >1.05, anterior chest wall deformity, abnormal spine curvature, protrusio acetabuli, joint hypermobility (wrist and thumb sign), arachnodactyly, camptodactyly, craniofacial (long narrow skull, deep eyes, recessed mandible, high palate, downslanting palpebral fissure)

CARDIAC
Thickening of AV valves, aortic valve dysfunction (aneurysm, rupture, dissection), long QT

OCULAR 
Ectopia lentis (UPward dislocation), flat cornea, increased axial globe length, hypoplastic iris, ciliary muscle hypoplasia

Question 7

How do you manage Marfan?

Answer 7

1. Activity restriction
2. Aortic surgery +/- mitral valve repair
3. Endocarditis prophylaxis
4. Beta-blocker

MS = autosomal dominant
Abnormal production, matrix deposition and/or stability of fibrillin-1

Question 8

What syndrome is associated with hypoplasia of middle phalynx of fifth digit?

Answer 8

Down syndrome

Question 9

What chromosome is affected in Prader-Willi syndrome (PWS)?

Answer 9

Chromosome 15

= absence of expression of the paternally active genes on the long arm of chromosome 15

Question 10

What is the most common syndrome cause of obesity?

Answer 10

Prader-Willi syndrome

Question 11

What are the antenatal manifestations of Prader-Willi syndrome (PWS)?

Answer 11

Reduced fetal activity
SGA
Polyhydramnios
Breech positioning

Question 12

What are the manifestations of Prader-Willi syndrome (PWS) by age?

Answer 12

INFANCY 
Neonatal hypotonia 
Feeding difficulty (poor suck) 
weak cry 
Genital hypoplasia 

EARLY CHILDHOOD 
Late motor milestones 
Short stature
Failed growth spurt 
Hyperphagia (age 1-6) 
Obesity (abnormal body composition) 

LATE CHILDHOOD/ADOLESCENCE
Adrenarche
Delayed secondary sexual characteristics
Behavioural issues

Question 13

What are the behavioural characteristics seen in Prader-Willi syndrome?

Answer 13

Temper tantrums
Stubborness
Obsessive compulsive behaviours

Question 14

What conditions are associated with mid-face hypoplasia?

Answer 14

CRANIOFACIAL SYNDROMES 
Crouzon 
Apert 
Marshall-Stickler 
Pfeiffer 

OTHER
Hydantoin syndrome (= fetal exposure maternal phenytoin or carbamazepine)
Achondroplasia
Cleft palate

= upper jaw, cheekbones and eye sockets not grown as much as rest of face -> bug-eyed appearance, under-bite