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Medical Genetics

Down syndrome (trisomy 21)

Down syndrome is a chromosomal condition caused by an extra copy of chromosome 21, with variable learning disability, hypotonia and characteristic features plus a higher chance of treatable cardiac, gastrointestinal, endocrine, hearing, visual, sleep, haematological and neurological problems.

In a nutshell

Down syndrome is trisomy 21 with variable learning disability, hypotonia and characteristic features plus predictable treatable comorbidity. Confirm the chromosome mechanism, assess every newborn for congenital heart disease, respond urgently to bilious vomiting or haematological abnormalities, and use DSMIG/NHS surveillance for thyroid, hearing, vision, growth, sleep, cervical-spine symptoms and development. Antenatal combined, quadruple and NIPT tests screen; CVS or amniocentesis diagnoses.

Classic presentation

A neonate has hypotonia, upslanting palpebral fissures, epicanthic folds, a single palmar crease and feeding difficulty; chromosome analysis confirms trisomy 21 and echocardiography identifies an atrioventricular septal defect.

Key points

  • Most cases are free trisomy 21 from nondisjunction; a translocation requires parental karyotypes and tailored recurrence counselling.
  • Antenatal screening and NIPT estimate chance; CVS or amniocentesis is diagnostic.
  • All newborns need paediatric cardiac assessment and echocardiography even without a murmur.
  • Bilious vomiting, failure to pass meconium, cyanosis, poor feeding, pallor, bruising or hepatosplenomegaly require urgent assessment.
  • Use DSMIG/NHS surveillance for thyroid, hearing, vision, growth, sleep, cervical-spine symptoms and development; offer NICE annual health checks to adults with learning disabilities.
  • New regression or cognitive change needs a medical, mental-health and dementia assessment rather than being dismissed as part of Down syndrome.

First-line investigation

Targeted antenatal screening or postnatal chromosome analysis, newborn echocardiography, and baseline haematology, thyroid, feeding, hearing and vision assessment.

Management

Confirm and find urgent disease

  • Confirm the chromosomal diagnosis and arrange paediatric cardiac review and echocardiography for every newborn, even without a murmur.1,9
  • Treat cyanosis, heart failure, bilious vomiting, abdominal distension, failure to pass meconium, airway compromise or abnormal neonatal blood counts as urgent paediatric problems.9,7

Counsel and treat structural disease

  • Explain that combined, quadruple and NIPT tests screen; CVS or amniocentesis is diagnostic, and offer balanced non-directive counselling.3,4,5
  • Use paediatric cardiology and paediatric surgery for congenital heart or gastrointestinal disease, with feeding, swallowing, airway and sleep support as needed.9,7

Surveil and respond to high-risk change

  • Use DSMIG/NHS surveillance for thyroid, hearing, vision, growth, sleep, cervical-spine symptoms and development; avoid routine asymptomatic cervical-spine imaging.6,7,10
  • Offer NICE annual health checks to adults with learning disabilities and assess any new loss of skills, mental-health symptoms or cognitive decline.8,12
  • Ask directly about communication, pain, hearing, vision, mental health, relationships and goals, using accessible information and reasonable adjustments.8,11

Support development and independence

  • Provide coordinated speech and language, physiotherapy, occupational, educational and social-care support, with transition planning and person-centred adult care.11,12,8

Exam traps

  • A positive combined, quadruple or NIPT result is not diagnostic; confirm with CVS or amniocentesis.
  • A translocation can be inherited and recurrence is not determined by maternal age alone.
  • Atrioventricular septal defect is the characteristic cardiac association, but every newborn needs echocardiography for all congenital lesions.
  • Do not order routine cervical-spine radiographs or impose blanket restrictions in an asymptomatic person; assess symptoms and follow DSMIG guidance.
  • Transient abnormal myelopoiesis occurs in newborns and can be serious; blasts, cytopenias or hepatosplenomegaly need paediatric haematology review.
  • New loss of skills or behaviour change needs assessment for pain, hearing, thyroid, sleep, mental-health, neurological and dementia causes.

Illustrations

Karyotype of trisomy 21A labelled karyogram showing three copies of chromosome 21, the defining chromosomal finding in Down syndrome.Courtesy: National Human Genome Research Institute, Wikimedia Commons · Public domain
Characteristic facial and hand featuresA respectful labelled illustration of common facial and hand features associated with Down syndrome, making clear that not every person has every feature and that features do not determine ability.Vanellus Foto, Wikimedia Commons · CC-BY-SA-3.0
Duodenal atresia double bubbleAn abdominal radiograph showing the double-bubble sign of duodenal atresia, an important association requiring urgent surgical assessment when bilious vomiting is present.Kinderradiologie Olgahospital Klinikum Stuttgart, Wikimedia Commons · CC-BY-SA-3.0

Key sources

  1. NHS Genomics Education, Down syndrome (trisomy 21) (UK genomic education resource covering clinical features, congenital associations, haematology and counselling after a confirmed diagnosis)Updated 1 Jan 2025
  2. NHS, Down’s syndrome (NHS overview, variable learning disability, screening choice and family or genetics support)Updated 17 Feb 2023
  3. NHS England, Fetal Anomaly Screening Programme overview (Current England screening offer, combined and quadruple testing, contingent NIPT and diagnostic CVS or amniocentesis)Updated 8 Jul 2024
  4. NHS England, Down’s syndrome screening pathway (Current England pathway updated January 2025 for combined or quadruple results, NIPT and diagnostic testing)Updated 30 Jan 2025
  5. NHS England, NIPT for Down’s, Edwards’ and Patau’s syndromes (Current information that NIPT is contingent screening, not diagnostic, and positive results need diagnostic confirmation)Updated 30 Jan 2025
  6. Down Syndrome Medical Interest Group, essential medical surveillance (UK and Ireland minimum surveillance framework covering cardiac, cervical spine, thyroid, hearing, ophthalmic and growth monitoring; 2024 cervical-spine and 2025 ophthalmic revisions noted)Updated 1 Oct 2025
  7. NHS Greater Glasgow and Clyde, health assessment of children and young people with Down’s syndrome (Current NHS paediatric surveillance guidance reviewed January 2025, based on DSMIG recommendations)Updated 14 Jan 2025
  8. NICE NG54, mental health problems in people with learning disabilities (NICE annual health-check, physical and mental-health review, communication and dementia-change recommendations)Updated 28 Sept 2016
  9. National Neonatal Network, Scottish standard care pathway for babies born with Down’s syndrome (UK neonatal pathway for cardiac assessment, gastrointestinal, haematological, hearing, thyroid, feeding and discharge planning)Updated 1 Jan 2024
  10. NICE IND79, annual TSH test in learning disabilities (NICE indicator for annual thyroid-stimulating hormone testing in adults with Down syndrome)Updated 1 Jan 2025
  11. NHS, how to help children and young people with Down’s syndrome (NHS support, regular hearing, vision and health checks, development and communication advice)Updated 17 Feb 2023
  12. NHS, support for adults with Down’s syndrome (NHS adult support, independence, work, activity and social-care information)Updated 17 Feb 2023

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.