Down Syndrome — Causes, Symptoms & Treatment Guide — Symptoms, Causes & Treatment | MyMedicPlus

Down syndrome (DS) — also known as trisomy 21 — is the most common chromosomal condition in humans, affecting approximately 1 in 700-1,000 live births worldwide. It is caused by the presence of an additional copy of chromosome 21 (three copies instead of the normal two) in all or most cells of the body, resulting in a characteristic pattern of physical features, intellectual disability, and increased risk of specific medical conditions. Three chromosomal mechanisms occur: trisomy 21 (non-disjunction during meiosis — 95% of cases), Robertsonian translocation (4-5% — a structural chromosomal rearrangement), and mosaic Down syndrome (2-4% — some cells have trisomy 21, others are normal, resulting in milder features). Life expectancy has improved dramatically — from under 10 years in the 1940s to over 60 years today — reflecting advances in cardiac surgery, medical care, and social inclusion. People with Down syndrome have a wide range of abilities and can lead fulfilling, independent lives with appropriate support.

Down syndrome is caused by non-disjunction — the failure of chromosome 21 pairs to separate correctly during the formation of eggs (oocytes) or, less commonly, sperm. This results in an egg or sperm containing two copies of chromosome 21. When fertilised by a normal gamete, the resulting cell has three copies of chromosome 21. The primary risk factor is advanced maternal age: the risk of non-disjunction increases with age as oocytes age — the risk is approximately 1 in 1,400 at age 25, 1 in 1,100 at 30, 1 in 400 at 35, 1 in 100 at 40, and 1 in 30 at 45. However, because more babies are born to younger mothers, the majority (approximately 80%) of babies with Down syndrome are born to mothers under 35. Robertsonian translocation is inherited — if a parent carries the translocation, the risk of recurrence in subsequent pregnancies is significantly elevated (10-15% maternal carrier, 2-5% paternal carrier) and genetic counselling is essential. Mosaic Down syndrome may occur from post-fertilisation mitotic errors.

Physical features (not all present in every individual): characteristic facial features — upslanted palpebral fissures (eye slant), epicanthal folds, flat nasal bridge, small low-set ears, protruding tongue (due to relative macroglossia and hypotonia), and single palmar crease; hypotonia (reduced muscle tone — present from birth, causing feeding difficulties and delayed motor milestones); short stature with stocky build; brachycephaly (flat occiput — back of head); Brushfield spots (white speckles around the iris); broad short hands and feet with wide gap between first and second toes (sandal gap). Intellectual disability: ranges from mild to moderate in most individuals — IQ typically 40-70; learning, memory, and language are affected, but individuals vary considerably. Associated health conditions: congenital heart defects (40-50% — atrioventricular septal defect and VSD are most common; require early echocardiography and surgical correction), hypothyroidism (15-20% — annual TSH testing required), hearing loss (75% — regular audiological review), visual problems (60% — refractive error, strabismus, cataracts), atlantoaxial instability (ligamentous laxity of C1-C2 — neck X-rays for sports clearance), obstructive sleep apnoea (50-60%), coeliac disease (5-10%), and haematological conditions — transient myeloproliferative disorder (TMD) in newborns; 1% risk of acute myeloid leukaemia (AML); also lower risk of solid tumours. Adults with Down syndrome have dramatically increased risk of Alzheimer's disease (by age 65, nearly all have the pathological changes of AD, and 50-70% develop clinical dementia).

Prenatal screening: first-trimester combined screening (11-14 weeks) — nuchal translucency (NT) ultrasound measurement plus maternal serum hCG and PAPP-A; risk is calculated and if high (above 1 in 150) diagnostic testing is offered. Non-invasive prenatal testing (NIPT/NIPS — cell-free fetal DNA from maternal blood): highly accurate (sensitivity above 99%, specificity above 99.9% for trisomy 21); now widely available from 10 weeks gestation; does not replace confirmatory invasive testing before termination of pregnancy decisions. Diagnostic prenatal testing: chorionic villus sampling (CVS — 11-14 weeks) or amniocentesis (15-20 weeks) provides karyotype confirmation — risk of miscarriage 0.5-1%. Postnatal diagnosis: clinical suspicion from characteristic physical features prompts urgent chromosomal analysis (karyotype from blood sample) — result available within 48-72 hours (FISH/QF-PCR) or 2-3 weeks (full karyotype). Health surveillance for people with Down syndrome includes: annual thyroid function tests from 6 months of age, cardiac echocardiography at birth, regular hearing and vision assessments, sleep study (polysomnography) from age 3-4, and coeliac antibody screening.

There is no cure for Down syndrome, but comprehensive multidisciplinary care significantly improves outcomes and quality of life. Early intervention programmes (birth to 5 years): physiotherapy (improves muscle tone, gross and fine motor development); speech and language therapy (augmentative communication, feeding support, language development); occupational therapy (self-care, fine motor, sensory processing); special educational needs (SEN) support from school entry. Congenital heart defect management: echocardiography in all newborns — atrioventricular septal defect (AVSD) and ventricular septal defect (VSD) require surgical repair, typically in the first 6 months of life; outcomes from cardiac surgery are now equivalent to children without Down syndrome. Hypothyroidism: levothyroxine replacement — annual TSH monitoring lifelong. Hearing loss: hearing aids, grommets for glue ear — essential for language and cognitive development. Visual problems: glasses, patching for amblyopia, surgery for cataract and strabismus. Obstructive sleep apnoea: adenotonsillectomy in children; CPAP for older children and adults. Atlantoaxial instability: cervical spine X-rays before participation in contact sports; surgical stabilisation in symptomatic cases. Alzheimer's disease in adults with DS: monitoring, cognitive support, and disease-modifying trials are ongoing. Educational inclusion, supported employment, residential living support, and meaningful social participation are central to modern Down syndrome care.

Congenital heart defects (CHD) are present in 40–50% of individuals with Down syndrome — atrioventricular septal defect (AVSD) and ventricular septal defect (VSD) are the most common and potentially life-threatening; without surgical correction in the first 6 months, pulmonary hypertension and Eisenmenger syndrome develop irreversibly. Alzheimer's disease is a near-universal complication in adults — by age 40, virtually all have the neuropathological hallmarks (amyloid plaques, neurofibrillary tangles due to APP gene on chromosome 21 being triplicated), and 50–70% develop clinical dementia by age 65. Haematological: transient myeloproliferative disorder (TMD) affects up to 10% of newborns with DS — usually self-limiting, but 20–30% of TMD cases progress to acute myeloid leukaemia (AML) by age 4; overall leukaemia risk is 10–20 times higher than in the general population. Atlantoaxial instability (AAI) from ligamentous laxity at C1–C2 occurs in 10–15% and can cause cervical myelopathy with potentially catastrophic neurological injury during contact sports or general anaesthesia — pre-anaesthetic cervical spine X-rays are mandatory. Obstructive sleep apnoea affects 50–60% and contributes to pulmonary hypertension, cognitive impairment, and behavioural difficulties if untreated; formal polysomnography is recommended from age 3–4. Hypothyroidism develops in 15–20%, impairing growth and cognitive development if undetected — annual TSH monitoring from infancy is essential. Gastrointestinal complications include duodenal atresia (1–3%) requiring surgical correction at birth, Hirschsprung disease (2–15%), and coeliac disease (5–10%). Recurrent otitis media and sensorineural hearing loss (75%) compound developmental delays if untreated.

Down syndrome resulting from non-disjunction trisomy 21 cannot currently be prevented. Preconception genetic counselling is recommended for: parents who have had a child with Down syndrome (particularly Robertsonian translocation — high recurrence risk); parents who are known carriers of Robertsonian translocations; and women of advanced maternal age who wish to understand their individualised risk. Preimplantation genetic testing (PGT-A) during IVF allows embryo testing for chromosomal abnormalities before uterine transfer — choosing to transfer chromosomally normal embryos. Prenatal screening (NIPT, combined screening) enables detection of Down syndrome during pregnancy — parents receive information and counselling to make informed reproductive decisions. For children and adults with Down syndrome: health surveillance protocols detect and treat associated conditions early; a healthy lifestyle (balanced diet, regular physical activity adapted to ability) reduces obesity and cardiovascular risk; and social participation, supported employment, and inclusive education maximise quality of life.

Prenatal: women with high-risk screening results should receive immediate genetic counselling and discuss diagnostic testing options (CVS or amniocentesis) without delay. Postnatal: any newborn with features suggesting Down syndrome should have urgent chromosomal analysis and paediatric assessment within 24-48 hours, including cardiac echocardiography (AVSD is the most common life-threatening associated condition). For children with confirmed Down syndrome: attend all scheduled health surveillance appointments (thyroid, hearing, vision, growth monitoring). Seek urgent paediatric review for: unexplained pallor or bruising in a newborn (transient myeloproliferative disorder), new heart failure symptoms, sudden change in motor function (atlantoaxial subluxation), and signs of acute leukaemia. Adults with Down syndrome should have annual health reviews and be monitored for early signs of Alzheimer's disease from age 40. Any rapid cognitive or behavioural change in an adult with DS warrants urgent investigation.