Down syndrome

Question 1

Down syndrome

Answer 1

Trisomy 21
Most common trisomy compatible with life
Extra material can result from non-dysjunction, translocation or mosaicism

Question 2

Non-dysjunction

Answer 2

95% of children with Down syndrome
Pair of c21 fail to separate at meiosis, so one gamete has two copies of c21
Fertilization of this gamete => zygote with 3 copies
90% maternally derived and risk rises with maternal age

Question 3

Translocation

Answer 3

4% of children with Down syndrome

Translocation of third c21 to another chromosome (most commonly 14)

Question 4

Mosaicism

Answer 4

1% of children with Down syndrome
Non-dysjunction occurs during mitosis after formation of the zygote so that some cells are normal and some show trisomy 21
Phenotype may be milder

Question 5

Clinical features - face

Answer 5

Round/flat face
Epicanthic folds
Upslanting palpebral fissures
Flat nasal bridge
Protruding tongue
Small ears
Brushfield spots in iris

Question 6

Clinical features - non-face dysmorphias

Answer 6

Single palmar crease
Flat occiput
Incurved little fingers
Sandal toe gap
Small stature

Question 7

Clinical features - structural defects

Answer 7

Cardiac defects in 50%

Duodenal atresia

Question 8

Clinical features - neurological

Answer 8

Hypotonia
Hirschsprung’s disease (functional obstruction)
Developmental delay
Learning difficulties: mean IQ = 50

Question 9

Late medical complications

Answer 9

Increased risk of leukaemia (ALL)
Repeated respiratory infections (and hearing impairment from glue ear)
Hypothyroidism
Alzheimer's disease
Atlantoaxial instability
Coeliac disease
Hearing and vision problems
Subfertility (males - almost always; females - usually) and increased incidence of pregnancy and labour problems

Question 10

Investigations

Answer 10

Antenatal screening
Rapid chromosomal analysis via FISH (fluorescence in situ hybridisation) but may not exclude mosaicism
Complete karyotype performed to confirm initial result

Question 11

Management

Answer 11

Parental counselling
Self-help groups
Genetic counselling for recurrence risk
Cardiology review and echo
Social input - employment and living arrangements
Screening for diseases throughout life

Question 12

Cardiac abnormalities

Answer 12

Multiple cardiac problems may be present
Endocardial cushion defect aka atrioventricular septal canal defect (40%)
VSD (30%)
Secundum atrial septal defect (30%)
Tetralogy of Fallot (5%)
Isolated PDA (5%)