Down Syndrome — Symptoms, Causes & Treatment | MyMedicPlus

Down syndrome (Trisomy 21) is a chromosomal condition caused by the presence of a full or partial extra copy of chromosome 21, resulting in 47 chromosomes instead of the usual 46. It is the most common chromosomal disorder, occurring in approximately 1 in 700 live births worldwide — affecting around 6 million people globally and approximately 6,000 births annually in the US. Down syndrome causes intellectual disability ranging from mild to moderate in the vast majority of individuals, along with characteristic physical features and a spectrum of associated health conditions including congenital heart disease, hypothyroidism, hearing impairment, and increased risk of early-onset Alzheimer's disease. It is not a disease but a lifelong condition. With early intervention therapies, appropriate medical management, inclusive education, and supported employment, individuals with Down syndrome lead fulfilling, meaningful lives — many live independently, form relationships, and are employed members of their communities. Life expectancy has improved dramatically, from approximately 25 years in 1980 to over 60 years today.

Standard Trisomy 21 (95% of cases): results from nondisjunction — a failure of chromosome 21 to separate during meiosis in egg or sperm formation, producing a gamete with an extra chromosome 21. This is typically a random, de novo event. Advanced maternal age is the strongest known risk factor: probability rises from 1 in 1,500 at age 20, to 1 in 350 at age 35, to 1 in 100 at age 40, and 1 in 30 at age 45. Translocation Down syndrome (approximately 4% of cases): extra chromosome 21 material is attached to another chromosome (usually chromosome 14 — Robertsonian translocation). Unlike standard Trisomy 21, this form can be inherited from a chromosomally balanced carrier parent — genetic counselling is essential for affected families. Mosaic Down syndrome (approximately 1%): some cells carry the extra chromosome and others do not, resulting from an error in cell division after fertilisation — often associated with milder features. No known preventable cause or modifiable lifestyle risk factor for standard Trisomy 21 has been established. Parents who have had one child with Trisomy 21 have an approximately 1% increased recurrence risk above age-related baseline.

Characteristic physical features: upward-slanting palpebral fissures (almond-shaped eyes with epicanthal folds), Brushfield spots on the iris, a flat facial profile (flat nasal bridge), small ears and mouth with a relatively large protruding tongue (macroglossia), a single palmar crease (simian crease — present in 50%), low muscle tone (hypotonia — present from birth, causing feeding difficulties in infancy), short stature, a broad short neck with loose skin at the nape, and widely spaced toes with a sandal gap (wide space between first and second toes). Associated health conditions: intellectual disability (IQ typically 35-70, with wide individual variation — mild to moderate in most, severe in some; early intervention significantly improves outcomes); congenital heart defects in 40-50% — the most common being atrioventricular septal defect (AVSD) and ventricular septal defect (VSD) — the leading life-threatening complication; hearing loss (40-60% — predominantly conductive from chronic otitis media/glue ear, also sensorineural); visual impairment (refractive errors, strabismus, cataracts — annual optometry essential); hypothyroidism (15-20% — requires annual thyroid function monitoring); coeliac disease (5-10%); atlantoaxial instability (1-2% — cervical spine C1-C2 instability with spinal cord compression risk); leukaemia risk elevated 10-20x (predominantly ALL and AML); and early-onset Alzheimer's disease — APP gene on chromosome 21 drives excess amyloid production, with Alzheimer's pathology present in nearly all by age 40 and clinical dementia in the majority who survive past 50.

Prenatal screening: first-trimester combined test (nuchal translucency ultrasound at 11-13+6 weeks plus serum PAPP-A and free beta-hCG) generates a risk score — detects approximately 85% of cases. Second-trimester quadruple screen (AFP, hCG, unconjugated oestriol, inhibin A) is an alternative. Non-invasive prenatal testing (NIPT / cfDNA): analysis of cell-free fetal DNA from maternal blood from 10 weeks — sensitivity and specificity both exceed 99% for Trisomy 21 with a very low false-positive rate; now recommended as the primary screening approach in many national guidelines. A positive NIPT must always be confirmed by diagnostic testing before any clinical decision is made. Confirmatory diagnostic tests: chorionic villus sampling (CVS — transabdominal or transcervical placental biopsy at 11-14 weeks) or amniocentesis (amniotic fluid at 15-20 weeks) provide fetal karyotype with near 100% accuracy; both carry a small procedure-related miscarriage risk (approximately 0.5-1%). Postnatal diagnosis: neonatal clinical features prompt urgent FISH (fluorescence in situ hybridisation — result within 24-48 hours) plus full karyotype (required to distinguish standard Trisomy 21 from translocation — essential for recurrence risk counselling). Newborn investigations: echocardiogram, hearing screen, thyroid function, full blood count (transient myeloproliferative disorder affects 10% of neonates with Down syndrome and requires haematology review).

There is no cure for Down syndrome — the genetic condition cannot be altered. Management focuses on optimising development and treating associated conditions. Early intervention (beginning in infancy) is the most impactful investment: speech and language therapy (targeting oral motor tone, language acquisition, and communication — assistive communication devices if needed); occupational therapy (fine motor skills, sensory processing, and activities of daily living); and physiotherapy (gross motor development, strength, and balance — hypotonia delays motor milestones but children do walk). Cardiac: congenital heart defects (40-50%) require echocardiographic assessment at birth and surgical repair in infancy — atrioventricular septal defect repair typically at 3-6 months — early repair prevents irreversible pulmonary hypertension. Hypothyroidism (15-20%): treated with levothyroxine titrated to maintain TSH within the normal range — annual TFT testing is lifelong. Health surveillance (national Down syndrome health guidelines recommend): annual thyroid function tests from birth; annual audiological assessment; regular optometry; atlantoaxial instability screening at age 3-4 (cervical spine X-ray) and before anaesthesia; coeliac antibody testing; haematological monitoring (elevated leukaemia risk). Educational support: individualised education plans (IEPs); inclusive mainstream school settings where possible; supported transition to further education and employment in adulthood. Psychological and behavioural support for anxiety, attention difficulties, and mood disorders — common in adolescence and adulthood.

Down syndrome is associated with a range of medical complications requiring lifelong structured health surveillance. Congenital heart disease (40-50%): the most life-threatening early complication — atrioventricular septal defect (AVSD) and ventricular septal defect (VSD) cause pulmonary hypertension and heart failure if not repaired in infancy; untreated cardiac defects cause Eisenmenger syndrome (irreversible pulmonary hypertension — inoperable) by school age. Recurrent otitis media and glue ear (40-60%): causes conductive hearing loss which, if untreated during critical language development periods, significantly impairs communication and education outcomes. Atlantoaxial instability (C1-C2 hypermobility in 1-2%): can progress to spinal cord compression presenting as loss of hand function, neck pain, or gait disturbance — requires urgent neuroimaging and neurosurgical assessment. Alzheimer's disease: the APP gene on chromosome 21 causes excess amyloid precursor protein production — Alzheimer's pathology is almost universal by age 40, and clinical dementia affects the majority who survive past 50; currently no disease-modifying therapy is available. Leukaemia: 10-20x elevated risk — predominantly acute lymphoblastic leukaemia (ALL) in childhood and AML with GATA1 mutations in neonates (transient myeloproliferative disorder in 10% of newborns, which usually resolves but predisposes to AML). Obstructive sleep apnoea (50-80%): from hypotonia, macroglossia, and midface hypoplasia — causes behavioural problems, poor school performance, and cardiovascular strain if untreated.

Down syndrome itself cannot be prevented — it results from random chromosomal events during gamete formation, and no modifiable lifestyle risk factors have been identified for standard Trisomy 21. Translocation Down syndrome (approximately 4% of cases) can be inherited from a balanced chromosomal carrier parent — genetic counselling and carrier testing for the extended family is essential to quantify recurrence risk accurately. Prenatal screening using NIPT (from 10 weeks gestation) combined with confirmatory CVS or amniocentesis provides accurate diagnosis for informed reproductive decision-making. For individuals living with Down syndrome, the focus is optimising health and development: enrol in early intervention from birth; maintain lifelong structured health surveillance (annual thyroid function tests, audiological review, cardiac follow-up, optometry, haematological monitoring); access inclusive mainstream education with appropriate SENCO support; pursue supported employment and semi-independent living in adulthood where possible. Connect families with Down Syndrome UK, the National Down Syndrome Society, or local support groups — peer support and advocacy significantly improve family outcomes and reduce isolation. Transition from paediatric to adult healthcare should be planned carefully from age 14, with specialist adult services formally engaged from age 18 to ensure continuity of medical monitoring and community support.

Every baby born with Down syndrome (or suspected Down syndrome based on antenatal screening or neonatal clinical features) should be referred immediately after birth to a neonatologist and paediatrician for clinical assessment and chromosomal confirmation (karyotype or FISH). Early medical checks are essential: echocardiogram for congenital heart disease (present in 40-50%), feeding assessment, hearing test, and eye examination in the newborn period. Parents should be referred to a Down syndrome specialist paediatric team and connected with a Down syndrome support organisation (e.g., Down Syndrome UK, Down Syndrome Association). Seek urgent medical assessment for: new onset of hand function regression, balance problems, or neck pain (atlantoaxial instability — may indicate spinal cord compression); new seizures; rapid cognitive decline in adulthood (early Alzheimer disease — which can begin in the 30s and 40s in Down syndrome); significant unexplained weight gain with fatigue and constipation (hypothyroidism — screen annually). Transition planning from paediatric to adult healthcare services should begin at age 14 with specialist adult services engaged from age 18.