Down's syndrome Flashcards
Define Down’s syndrome
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
What is the aetiology of Down’s syndrome
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
What are the risk factors for Down’s syndrome
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
What are the symptoms of Down’s syndrome
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
What are the characteristic physical features of Down’s syndrome
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
What are the differentials for Down’s syndrome
Isolated hypotonia
Zellweger’s syndrome (hypotonia, flat occiput and face, epicanthal folds, brushfield spots, cataracts, seizures, single palmar crease, NORMAL karyotype)
Congenital hypothryoidism
What investigations should be done for Down’s syndrome
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
What is the management for Down’s syndrome
- 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
How is Down’s syndrome screened for in pregnancy
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)
What are the complications of Down’s syndrome
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
What is the prognosis for Down’s syndrome
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