Genetics

Question 1

Down syndrome

What is the genetic abnormality?

Clinical features?

Answer 1

• Trisomy 21
• Learning disability
• Congenital heart disease
• Hypothyroidism
• Immunity
• Early onset Alzheimer disease

Question 2

What are the outcomes of congenital anomalies?

Answer 2

• 3% all births
• 20% children’s hospital admissions
• 30% infant deaths

Question 3

How can we recognise a rare intellectual disability +/- malformation?

Answer 3

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

Question 4

Features to look for on head?

Answer 4

• Shape
• Size: macrocephaly, microcephaly
• Ear position
  
  • Low set, posteriorly rotated indicates lack of maturity

Question 5

Features to look for on eyes?

Answer 5

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

Question 6

Features to look for on hands?

Answer 6

• Finger length
• Digital abnormalities
• Palmar creases

Question 7

What is Acrocephalopolysyndactyly?

Answer 7

• Tall forehead
• Polydactyly
• Syndactyly

Question 8

What is Deformation & Disruption?

Answer 8

• 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 9

What is VATER association?

Answer 9

two features or more features occur together more often than expected by chance

• V vertebral / VSD
• A anorectal atresia
• T tracheo-
• E (o)esophageal fistula
• R radial anomalies

Question 10

Turner syndrome

What is the genetic abnormality?

What are the clinical features?

Answer 10

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

Question 11

How do we investigate a learning disability?

Answer 11

• Microarray
• Fragile X
• Targetted tests driven by phenotype

Question 12

22q11 deletion

Clinical features of 22q11 deletion?

Answer 12

• Cleft palate
• Abnormal facies
• Thymic hypoplasia / immune deficiency
• Calcium
• Heart problems
• Caused by 22 deletion
  
  • “CATCH 22”