Down's syndrome

Question 1

Define Down’s syndrome

Answer 1

A form of intellectual disability caused by trisomy 21, which results in characteristic physical features, short stature, cognitive and behavioural profiles, as well as a higher frequency of associated medical conditions

Question 2

What is the aetiology of Down’s syndrome

Answer 2

Meiotic non-disjunction or failure of chromosome pairs to separate during gamete formation → trisomy 21 (no need to check parental Chr)
4% have Robertsonian translocation between 21q and the long arm of the other acrocentric chromosome (check parental Chr - risk of recurrence)
1% have mosaic type

Question 3

What are the risk factors for Down’s syndrome

Answer 3

Increasing maternal age (1 in 1000 <30 years, 1 in 100 aged 40, 1 in 12 aged 49)
Sibling with Down’s syndrome (chance 1 in 100)
Abnormal parental karyotype

Question 4

What are the symptoms of Down’s syndrome

Answer 4

Typically diagnosed as a newborn due to the characteristic physical presentation

• Cognitive disability: visuo-spatial tasks, IQ range from mild-moderate ID
• Developmental delay (expressive language)
• Hearing loss (chronic ear infections)
• ASD
• Congenital GI disorders e.g. duodenal/anal stenosis/atresia
• Constipation
• Feeding difficulties e.g difficulty sucking or coordinating feeding (Hypotonia, underweight, slow/choking feeds, recurrent/persistent resp/ symptoms, desaturation with feeding)
• Behavioural difficulties, especially with peers
• Social and affectionate
• Characteristic physical features

Question 5

What are the characteristic physical features of Down’s syndrome

Answer 5

Flat face and occiput
Epicanthal folds
Upslanting palpebral fissure
Brushfield spots on irirs
Short nose, low nasal bridge, small nares (nostrils)
Round cheeks
Small ears, may be low-set
Protruding tongue, small mouth
Broad neck, extra skin
Single palmar crease, short hands, fifth finger clinodactyly
Wide sandal gap

Question 6

What are the differentials for Down’s syndrome

Answer 6

Isolated hypotonia
Zellweger’s syndrome (hypotonia, flat occiput and face, epicanthal folds, brushfield spots, cataracts, seizures, single palmar crease, NORMAL karyotype)
Congenital hypothryoidism

Question 7

What investigations should be done for Down’s syndrome

Answer 7

Bloods
- Chromosomal karyotype: trisomy 21/Robertsonian translocation/mosaicism
- FBC: normal/abnormal (screen for TAM)
- TFTs: Normal (exclude hypothyroidism)
Other: echocardiogram, hearing tests, visual examination, AXR

Question 8

What is the management for Down’s syndrome

Answer 8

1. Immediate assessment ± specialist consult for any medical conditions
   - Echo
   - Genetic counselling
   - Early intervention for delay: PT, OT, SALT

Refer to child development services
- Regular review of development and health
- Liaise with schools → individualised educational plan
- Screen periodically (annually up to 5yo, then every 2 years): vision, hearing, TFTs, coeliac, atlantoaxial instability, Hb (IDA), sleep apnoea, growth

Resources: Down syndrome association, National down syndrome society

Question 9

How is Down’s syndrome screened for in pregnancy

Answer 9

All pregnant women are offered the combined test at 11-13+6 week
Triple test: ↑Nuchal translucency + ↑serum b-hCG + PAPP-A (pregnancy associated plasma protein A)
Quadruple (for those booking later, 15-20 weeks: ↓Alpha-fetoprotein + ↓unconjugated oestriol + ↑HCG + ↑inhibin A

→ if high chance (<1 in 150) → diagnostic test (cell-free foetal DNA, amniocentesis, Chorionic villus sampling)

Question 10

What are the complications of Down’s syndrome

Answer 10

Congenital heart defects: tetralogy of fallot, atrio-ventricular septal defect, ASD/VSD
GI: Duodenal atresia, Hirschprung’s disease, coeliac disease, Omphalocoele ± umbilical hernia
Hypothyroidism
Leukaemia and solid tumours (Transient abnormal myelopoiesis/AML)
Obstructive sleep apnoea
Audiological: otitis media, hearing impairment
Visual: congenital cataracts, strabisimus, myopia/hyperopia, blepharitis
Early onset alzheimer’s
Atlantoaxial instability: screen in those who participate in sports that may carry an increased risk of neck dislocation e.g. trampolining, gymnastics, boxing, diving, rugby horse riding

Question 11

What is the prognosis for Down’s syndrome

Answer 11

Difficult to predict long-term prognosis in the neonatal period
Congenital heart disease is a major cause of early mortality
Over 85% of infants with trisomy 21 survive to 1 year of age
At least 50% of individuals live longer than 50 years in the UK