Down Syndrome


Down syndrome, first described by Langdon Down in 1866, is caused by an extra copy of all or part of chromosome 21. It is the most commonly recognised genetic cause of intellectual disability and is characterised by a number of dysmorphic features and congenital malformations. The features of Down syndrome vary greatly from individual to individual, although some level of intellectual disability is always present as is hypotonia. The life expectancy of individuals with Down syndrome now approaches 60 years. The sequencing of the long arm of chromosome 21 was a milestone in research about Down syndrome but the complete understanding of the genetic information on the chromosome is still in progress. Several different mouse models with features reminiscent of aspects of Down syndrome have been produced. Although it is difficult to extrapolate from mice to humans, several studies using these mouse models suggest that it will be possible to develop therapies for aspects of Down syndrome, perhaps including intellectual disability.

Key Concepts:

  • The incidence of Down syndrome in the newborn population is in the vicinity of 1 per 700 live births in the United States and about 1 in 1000 in Europe. There is considerable variability in reported incidence in other parts of the world.

  • The condition of overriding critical importance in Down syndrome is intellectual disability.

  • The memory profile in Down syndrome is distinct from that seen in other phenotypic disorders associated with developmental disability such as Williams syndrome and Fragile x syndrome.

  • Pathological, metabolic and neurochemical changes of Alzheimer disease are present after the third decade in the brain of all individuals with Down syndrome.

  • With the changing patterns of institutionalisation and of the utilisation and methods of medical and surgical therapy, the mean life expectancy for persons with Down syndrome has improved dramatically in the last 50 years.

  • No pharmacological or dietary therapy as yet has been shown to have a beneficial effect on the intellectual disability associated with Down syndrome.

  • As one of the first triumphs of the Human Genome Project, the sequence of the long arm of chromosome 21 has been completed.

  • The successful amelioration of some of the learning and memory deficits and alterations in brain abnormalities in mouse models are encouraging since they support the hypothesis that successful post‚Äźnatal treatment of Down syndrome may be possible.

Keywords: intellectual disability; chromosome 21; trisomy; aneuploidy; Alzheimer disease; congenital heart disease; mouse models


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Further Reading

Antonarakis SE and Epstein CJ (2006) The challenge of Down syndrome. Trends in Molecular Medicine 12: 473–479.

Dellarco VL, Voytek PE and Hollaender A (eds) (1985) Aneuploidy: Etiology and Mechanisms. New York, NY: Plenum.

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Epstein CJ (ed.) (1991) The Morphogenesis of Down Syndrome. New York, NY: Wiley‐Liss.

Epstein CJ (ed.) (1993) The Phenotype Mapping of Down Syndrome and Other Aneuploid Conditions. New York, NY: Wiley‐Liss.

Epstein CJ, Hassold T, Lott IT, Nadel L and Patterson D (eds) (1995) Etiology and Pathogenesis of Down Syndrome. New York, NY: Wiley‐Liss.

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Nadel L and Epstein CJ (eds) (1992) Downs Syndrome and Alzheimer Disease. New York, NY: Wiley‐Liss.

Patterson D and Costa AC (2005) Down syndrome and genetics – a case of linked histories. Nature Reviews Genetics 6: 137–147.

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Patterson, David, and Lott, Ira T(Oct 2011) Down Syndrome. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005711.pub2]