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For further information, see CMDT Part 40-17: Down Syndrome

Key Features

Essentials of Diagnosis

  • Typical craniofacial features (flat occiput, epicanthal folds, large tongue)

  • Intellectual disability

  • Congenital heart disease (eg, atrioventricular canal defects) in 50% of patients

  • Three copies of chromosome 21 (trisomy 21) or a chromosome rearrangement that results in three copies of a region of the long arm of chromosome 21

General Considerations

  • Maternal age is risk factor of increasing the chance of having a child with Down syndrome

    • Risk increases exponentially with the age of the mother at conception

    • Risk rises markedly after age 35

    • By age 45 years, the odds of having an affected child are as high as 1 in 40

  • The risk of other conditions associated with trisomy also increases because of the predisposition of older oocytes to nondisjunction during meiosis

  • Increased paternal age is not associated with risk of trisomy


  • Nearly 0.5% of all human conceptions are trisomic for chromosome 21

  • Because of increased fetal mortality, birth incidence of Down syndrome is 1 per 700 but varies from 1 per 1000 in young mothers to more than three times as frequent in women of advanced maternal age

Clinical Findings

  • Typical craniofacial features

  • Hypotonia

  • Single palmar crease

  • Duodenal atresia

  • Congenital heart disease

  • Hematologic malignancy

  • An Alzheimer-like dementia usually becomes evident in the fourth or fifth decade


  • Cytogenomic analysis

  • Prenatal detection

    • "Multiple marker screening" (screening maternal serum for alpha-fetoprotein and other biomarkers) in the first trimester or early in the second trimester

    • Ultrasonography can visualize increased nuchal thickness and underdevelopment of the nasal bone

    • Assaying fetal DNA that is circulating in maternal blood can diagnose Down syndrome with high sensitivity and specificity


  • Duodenal atresia should be treated surgically

  • Congenital heart disease should be treated as in any other patient

  • Any leukemia typically responds to reduced-dose chemotherapy

  • No medical treatment has been proven to affect the neurodevelopmental or the neurodegenerative aspects

  • Supplementation with antioxidants has shown no benefit



  • Atlanto-axial instability

  • Celiac disease

  • Frequent infections due to immune deficiency

  • Hypothyroidism


  • Patients who survive childhood and in whom dementia develops have a reduced life expectancy; on average, they live to about age 55 years

  • The intestinal and cardiac anomalies usually respond to surgery

  • A transient neonatal leukemia generally responds to conservative management

  • If relapse of leukemia occurs, outcome is poor

When to Refer

  • For comprehensive evaluation of infants to investigate congenital heart disease, hematologic malignancy, and duodenal atresia

  • For genetic counseling of the parents

  • For signs of dementia ...

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