About This Page
This is a clinician-written, evidence-based summary aligned to the 2026 MLA Content Map. It is intended for medical students and junior doctors preparing for the UKMLA. Always cross-reference with NICE guidance, local protocols, and clinical judgement.
The Bottom Line
- Trisomy 21 — most common chromosomal abnormality (1 in 700–1,000 live births). Risk increases with maternal age
- Antenatal screening: combined test (11–14 weeks) — nuchal translucency + free beta-hCG (raised) + PAPP-A (low). NIPT (cell-free fetal DNA) for high-risk results
- Clinical features: hypotonia, flat facial profile, upslanting palpebral fissures, single palmar crease, Brushfield spots, sandal gap toes
- Cardiac associations: AVSD (most characteristic, ~40%), VSD, ASD, PDA, Tetralogy of Fallot — echo within 6 weeks of birth
- Health surveillance: annual TFTs (hypothyroidism in 15–20%), regular hearing and vision checks, coeliac screen, cervical spine assessment for atlantoaxial instability
- Increased risk of: ALL (10–20x), Alzheimer disease (early onset), obstructive sleep apnoea, coeliac disease, Hirschsprung disease
Overview
Down syndrome is caused by trisomy 21, with three copies of chromosome 21 present. In 95% of cases this is due to non-disjunction (complete extra chromosome 21), 4% due to Robertsonian translocation (most commonly 14;21), and 1% are mosaic. It is the most common genetic cause of learning disability. The phenotype is highly variable, ranging from mild to moderate intellectual disability, with a characteristic facial appearance and multiple systemic associations requiring lifelong health surveillance.
Epidemiology
Incidence is approximately 1 in 700–1,000 live births. The risk increases significantly with maternal age: 1 in 1,500 at age 20, 1 in 800 at age 30, 1 in 100 at age 40, 1 in 30 at age 45. The NHS Fetal Anomaly Screening Programme offers combined screening to all pregnant women. Median life expectancy has increased to 60+ years with improved cardiac surgery and healthcare.
Clinical Features
Symptoms
Neonatal hypotonia (floppy baby) — often the first clinical sign
Feeding difficulties in infancy
Developmental delay — variable severity, typically mild-moderate intellectual disability
Hearing impairment (conductive — glue ear; sensorineural — rarer)
Constipation (Hirschsprung disease in 2–3%)
Signs
Flat facial profile with flat nasal bridge
Upslanting palpebral fissures and epicanthic folds
Brushfield spots (white speckled iris — best seen in blue/grey eyes)
Single palmar crease (40%), clinodactyly of 5th finger, wide sandal gap between 1st and 2nd toes
Short stature, brachycephaly, short neck with excess nuchal skin
Cardiac murmur (congenital heart disease in 40–50%)
Investigations
First-line
Karyotype (chromosomal analysis)Confirms diagnosis — shows trisomy 21 (47,XX/XY,+21), translocation, or mosaicism
EchocardiographyWithin 6 weeks of birth — congenital heart disease in 40–50%. AVSD is the most characteristic
TFTsBaseline at birth and annually — hypothyroidism develops in 15–20%
Second-line
Hearing assessmentNewborn hearing screen then regular audiology (6-monthly to age 5, annually thereafter)
Vision assessmentRegular ophthalmological review — high rates of refractive errors, strabismus, cataracts
FBCNeonatal polycythaemia. Monitor for transient abnormal myelopoiesis (TAM). Increased leukaemia risk
Specialist
Coeliac screen (anti-tTG)By age 2 and if symptoms — prevalence 5–15%
Cervical spine X-rayLateral flexion-extension views if symptomatic or pre-anaesthetic — atlantoaxial instability in 10–20% (usually asymptomatic)
1
Neonatal period
- Confirm diagnosis with karyotype
- Echocardiography within 6 weeks
- TFTs at birth
- Newborn hearing screen
- Feeding support — lactation consultant, occupational therapy
2
Health surveillance
- Annual TFTs
- Hearing assessment 6-monthly to age 5, then annually
- Vision assessment annually in childhood
- Coeliac screen if symptomatic or by age 2
- Growth plotted on Down syndrome-specific growth charts
- Cervical spine assessment before anaesthesia
3
Developmental support
- Early intervention: physiotherapy, SALT, occupational therapy
- Educational support — EHCP for school
- Portage home visiting programme
- Transition planning for adulthood
4
Monitoring for complications
- Cardiac follow-up as needed
- Monitor for leukaemia (TAM, ALL, AML) — blood counts if symptoms
- Sleep study if obstructive sleep apnoea suspected (common)
- Mental health: increased rates of depression, anxiety, early-onset Alzheimer disease
Complications
- Congenital heart disease: 40–50% — AVSD most characteristic. Surgical repair improves survival
- Leukaemia: 10–20x increased risk of ALL; neonatal TAM in ~10% (usually resolves spontaneously)
- Hypothyroidism: 15–20% — annual screening essential
- Alzheimer disease: Very high risk, early onset (40s–50s) — almost universal amyloid pathology by age 40
- Atlantoaxial instability: 10–20%, usually asymptomatic. Symptomatic subluxation is rare but dangerous
- Obstructive sleep apnoea: Very common — midface hypoplasia, large tongue, hypotonia
UKMLA Exam Tips
- 1AVSD is the most characteristic cardiac defect in Down syndrome (not VSD — though VSD is more common in the general population)
- 2Combined test: raised free beta-hCG + low PAPP-A + increased nuchal translucency = high risk for trisomy 21
- 3Brushfield spots, single palmar crease, sandal gap, upslanting palpebral fissures — classic exam features
- 4Annual TFTs — hypothyroidism develops in 15–20%, often autoimmune
- 595% non-disjunction (maternal age-related), 4% Robertsonian translocation (may be inherited — offer parental karyotype), 1% mosaic
- 6ALL risk 10–20x increased. TAM (transient abnormal myelopoiesis) is unique to neonates with Down syndrome
practicetest your knowledge on down syndromeApply what you've learnt with UKMLA-style questions from the iatroX Q-Bank — paediatrics and beyond.
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