Elsevier

The Lancet

Volume 361, Issue 9365, 12 April 2003, Pages 1281-1289
The Lancet

Seminar
Down's syndrome

https://doi.org/10.1016/S0140-6736(03)12987-XGet rights and content

Summary

The sequencing of chromosome 21 and the use of models of Down's syndrome in mice have allowed us to relate genes and sets of genes to the neuropathogenesis of this syndrome, and to better understand its phenotype. Research in prenatal screening and diagnosis aims to find methods to identify fetuses with Down's syndrome, and reduce or eliminate the need for amniocentesis. Other areas of active research and clinical interest include the association of Down's syndrome with coeliac disease and Alzheimer's disease, and improved median age of death. Medical management of the syndrome requires an organised approach of assessment, monitoring, prevention, and vigilance. Improvements in quality of life of individuals with Down's syndrome have resulted from improvements in medical care, identification and treatment of psychiatric disorders (such as depression, disruptive behaviour disorders, and autism), and early educational interventions with support in typical educational settings. Approaches and outcomes differ throughout the world.

Section snippets

Genetics of chromosome 21 and Down's syndrome

In 1959 Lejeune, Gautier, and Turpin discovered the association between Down's syndrome and a third chromosome 21.1 The recent sequencing of chromosome 21, in principle, allows the identification of every gene on the chromosome.2 In the original manuscript, in which the sequencing and annotation for gene content was described, 225 genes or predicted genes were identified. The gene content of chromosome 21 is now estimated to be 329, including 165 experimentally confirmed genes, 150 gene models

Pregnancy screening, prenatal diagnosis, and epidemiology

The diagnosis of Down's syndrome is made by chromosome analysis, which can be initiated prenatally due to identified risk factors, or postnatally due to the characteristic appearance of the infant (panel 4).22 Prenatal diagnosis for chromosomal anomalies was first introduced in the 1970s, and was initially restricted to amniocentesis in the second trimester. At present, the standard of care in the USA is to offer pregnancy screening for chromosomal anomalies and spina bifida by a blood test to

Assessment and management

The American Academy of Pediatrics36 and the Down's Syndrome Medical Interest Group37 have developed guidelines for the medical management of individuals with Down's syndrome. Reviews that focus on the medical problems of adolescents38 and adults39 have also been developed. Assessment, monitoring, prevention, and vigilance play a part in management of children, adolescents, and adults with Down's syndrome (panel 5).36, 37

Alternative treatments

For decades, nutritional interventions have been popular but controversial treatments for Down's syndrome. Clinical trials of nutritional supplements have had methodological problems and have shown no efficacy.110 Theoretically, antioxidants may improve some of the clinical problems associated with Down's syndrome. Evidence links oxidative stress with immune dysfunction, malignancy, mild to severe learning disabilities, and premature ageing. In Down's syndrome, the activity of superoxide

Epidemiology of life expectancy

In the past decade and a half, investigators in many countries have noted a substantial improvement in the median age of death in individuals with Down's syndrome.112 In a survey of 17 897 individuals with Down's syndrome compiled by the US Centers of Disease Control and Prevention National Center for Health Statistics for 1983–97, the median age of death increased from 25 years in 1983 to 49 years in 1997 (p<0·0001).113 When assessed by racial group, the median age of death was significantly

Counselling and psychosocial issues

Many different disciplines and physician specialists participate in counselling parents about a child with Down's syndrome. They discuss prenatal screening, newborn diagnosis, health issues, informative publications,116, 117, 118, 119, 120, 121, 122, 123, 124, 125 parent groups, advocacy, educational choices, employment, and transitions to adult living opportunities. The quality of guidance and the way in which it is presented are very important. Fortunately, most experienced professionals have

Conclusion

Most of the positive improvements in the quality of life of people with Down's syndrome are the result of parental support. Typically, parents are disappointed when their newborn is diagnosed with Down's syndrome. However, within a few months, they become attached. Parents frequently report that the child with Down's syndrome is happier and more loveable than other children, although investigators have found children with Down's syndrome to be of similar temperament to other children. Clearly,

Search strategy and selection criteria

Data for this seminar were identified by searches of Medline with the search term Down syndrome and individual topics. We focused on publications in the past 5 years and included highly regarded older publications. We followed the Health Supervision for Children with Down Syndrome guidelines developed by the American Academy of Pediatrics Committee on Genetics17 and the guidelines of the Down Syndrome Medical Interest Group18 and discussed the areas of controversy.

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