Down syndrome

Last revised by Dr Yuranga Weerakkody on 31 Jul 2021

Down syndrome (or trisomy 21) is the most common trisomy and also the commonest chromosomal disorder. It is a major cause of intellectual disability, and also has numerous multisystem manifestations.

The approximate worldwide incidence is approximately 1 in 800 live births 15. The individual risk is strongly dependent on maternal risk, and therefore incidence varies with regional and temporal variation in maternal age distribution and the implementation of antenatal screening.

  • increased incidence with increasing maternal age
  • translocation Down syndrome gene carriers
  • previous pregnancy with Down syndrome

Diagnosis is often made antenatally and this must occur in conjunction with genetic counseling, which should begin prior to the testing.

In the postnatal period, characteristic phenotypical features point to the diagnosis:

Intellectual disability becomes evident in early childhood as the failure to reach developmental milestones in an expected timeframe.

In ~95% of cases, the chromosomal abnormality is trisomy of chromosome 21 due to meiotic non-disjunction (i.e. failure of a chromosome pair to separate during meiosis, so that both go to one daughter cell, and none to the other). Thus, the individual’s chromosome count is 47, rather than 46. Maternal non-disjunction accounts for ~95% of such cases.

An alternative chromosomal abnormality that results in the syndrome involves Robertsonian translocation of paternal chromosomal material, such that the overall number of chromosomes remains the same. This happens in ~3% of cases 9. Very rarely (~2%) some individuals have mosaic trisomy 21.

Cognitive disability and epilepsy are the most common neurological manifestations 8. Structurally evident abnormalities include:

Congenital heart disease affects ~40%. In particular, defects affecting the endocardial cushion are common:

  • significantly increased incidence of leukemia (although the individual may be protected against other solid organ tumors)

The manifestations of Down syndrome are protean and can affect multiple systems. Some of these are better discussed under individual features in the wide clinicopathological spectrum of the condition (listed above).

These are discussed in detail in a separate article.

Survival can be variable with the mean survival often considered at ~20 years-ref. Respiratory infections stay considerably predominant cause of death. Moreover, other causes of early mortality, include congenital heart defects and dementia 15.

Down syndrome was named after John Langdon Haydon Down (1828-1896), an English physician 13.

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Cases and figures

  • Case 1: with cystic hygroma
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  • Case 2: with esophageal atresia
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  • Case 3: with an AVSD
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  • Case 4: 11 ribs and omphalocoele
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  • Case 5: with "mickey mouse" pelvis
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  • Case 6: semicircular canal dysplasia
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  • Case 7: with an AVSD
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