Paediatric Genetics

Question 1

How to diagnose a rare intellectual disability and/or malformation syndrome

Answer 1

•	History
•	Description
•	Recognition of patterns
•	Testing
o	Standard- biochemical, chromosome structure
	Microarray now standard
o	Targeted testing
o	Moving to exome / genome

Question 2

description of the dysmorphic child

Answer 2

• Position and shape of facial features
• Hands
• Growth of child
• General features

Question 3

description of the dysmorphic child: head

Answer 3

•	Shape 
•	Size
o	Macrocephaly, microcephaly
•	Ear position
o	Low set, posteriorly rotated indicates lack of maturity

Question 4

description of the dysmorphic child: eyes

Answer 4

• Hypertelorism
o Inner canthal distance ICD and inter-pupillary distance IPD increased
• Telecanthus / epicanthic folds
o ICD and IPD increased

Question 5

description of the dysmorphic child: hand

Answer 5

Measurements

•	Finger length
•	Digital abnormalities
•	Palmar creases
•	Examples Marfan syndrome, Down syndrome 
o	Marfan’s – MF/THL is usually > 44%

Malformation

• Alone or as part of a syndrome
• E.g. polysyndactyly alone (Hox D13 one cause)
• Or acrocephalopolysyndatyly (Greig/GL13)

Acrocephalopolysyndactyly

• Tall forehead
• Polydactyly
• Syndactyly

Question 6

description of the dysmorphic child: sequence

Answer 6

•	One abnormality leads to another, can have multiple causes
•	Pierre-Robin sequence
o	small chin to cleft palate
•	Foetal akinesia sequence
o	Reduced foetal movement
o	Reduced breathing
o	Contractures
o	Clefting
o	Lung hypoplasia

Question 7

description of the dysmorphic child: deformation and disruption

Answer 7

• Pattern of development normal to start with but becomes abnormal
• Deformation: Organ parts are there
• Disruption: Parts of organ / body part absent
• E.g. Amniotic bands

Question 8

description of the dysmorphic child: association

Answer 8

•	Two features or more features occur together more often than expected by chance
•	Mechanism unclear
•	Vater
o	Vertebral anomalies/VSD
o	Ano-rectal atresia
o	Tracheo-oesophageal fistula
o	Radial anomalies

Question 9

description of the dysmorphic child: syndrome

Answer 9

Syndromes are a distinct group of symptoms and signs which, associated together, form a characteristic clinical picture or entity. Cause may or may not be known.

Question 10

Turner syndrome

Answer 10

• Lymphoedema (Puffy feet, nuchal translucency / cystic hygroma)
• Increased carrying angle, low hairline, wide sp nipples, sandal gap
• Short stature, occ. v mild learning diffy
• Coarctation of aorta, hypothyroidism, UTI, osteoporosis & hypertension
• Primary amenorrhoea & infertility
• Hormonal therapy mitigates some features

Question 11

22q11 deletion

Answer 11

• Cleft palate
• Abnormal facies
• Thymic hypoplasia / immune deficiency
• Calcium
• Heart problems