Research

Down syndrome is “a developmental abnormality characterized by trisomy of human chromosome 21" (Nelson 619). The extra copy of chromosome-21 leads to an over expression of certain genes located on chromosome-21. Research by Arron et al shows that some of the phenotypes (displayed genetic characteristics), associated with Down Syndrome can be related to the dysregulation of gene-regulating proteins (596).

The gene-regulating proteins bind to DNA and initiate certain segments of DNA to be replicated for the production of a certain protein (Arron et al. 596). The gene-regulator in interest is called NFATc. Its activities are controlled by two proteins, DSCR1 and DYRK1A; these genes are located on chromosome-21 (Epstein 582). In people with Down Syndrome, these proteins have 1.5 times greater concentration than normal (Arron et al. 597). The elevated levels of DSCR1 and DYRK1A mean that most of the NFATc is located in the cytoplasm rather than in the nucleus promoting DNA replication which will produce vital proteins (Epstein 583).

This dysregulation was discovered by testing in transgenic mice. The mice had segments of their chromosomes duplicated to simulate a human chromosome-21 trisomy (Arron et al. 597). A common characteristic of Down Syndrome is poor muscle tone, so a test involving the grip strength of the mice showed that the genetically modified mice had a significantly weaker grip (Arron et al. 596). The mice squeezed a probe with a paw; the modified mice displayed a .2 Newton (measurement of force) weaker grip (Arron et al. 596). Down syndrome is also characterised by increased socialisation. Both modified and unmodified mice were observed for social interaction. The modified mice showed as many as 25% more interactions per time period as the unmodified mice (Arron et al. 596).

The genes that may be responsible for the phenotypes associated may be located proximal to 21q22.3. Testing by Olson et al, in transgenic mice show the duplicated genes presumed to cause the phenotypes are not enough to cause the exact features. While the mice had sections of multiple genes duplicated to approximate a human chromosome-21 triplication, they only showed slight craniofacial abnormalities (688-690). The transgenic mice were compared to mice that had no gene duplication by measuring distances on various points on their skeletal structure and comparing them to the normal mice (Olson et al. 687). The exact characteristics of Down Syndrome were not observed, so more genes involved for Down Syndrome phenotypes have to be located elsewhere.

Reeves et al, using 250 clones of chromosome-21 and specific gene markers, were able to map the gene in mutated bacteria. The testing had 99.7% coverage of the gene with 99.9995% accuracy due to multiple redundancies in the mapping techniques. In the study 225 genes were identified (311-313). The search for major genes that may be involved in Down syndrome symptoms is normally in the region 21q21–21q22.3. However, studies by Reeves et al. show that 41% of the genes on chromosome-21 have no functional purpose, and only 54% of functional genes have a known protein sequence. Functionality of genes was determined by a computer using exon prediction analysis (312). Exon sequence was obtained by the same procedures of the chromosome-21 mapping.

Research has led to an understanding that two genes located on chromosome-21, that code for proteins that control gene regulators, DSCR1 and DYRK1A can be responsible for some of the phenotypes associated with Down Syndrome. DSCR1 and DYRK1A cannot be blamed outright for the symptoms; there are a lot of genes that have no known purpose. Much more research would be needed to produce any appropriate or ethically acceptable treatment options.

Recent use of transgenic mice to study specific genes in the Down syndrome critical region has yielded some results. APP is an Amyloid beta A4 precursor protein. It is suspected to have a major role in cognitive difficulties. Another gene, ETS2 is Avian Erythroblastosis Virus E26 Oncogene Homolog 2. Researchers have "demonstrated that over-expression of ETS2 results in apoptosis. Transgenic mice over-expressing ETS2 developed a smaller thymus and lymphocyte abnormalities, similar to features observed in Down syndrome." Vitamin supplements, in particular supplemental antioxidants and folinic acid, have been shown to be ineffective in the treatment of Down syndrome.

Sociological and cultural aspects

Advocates for people with Down syndrome point to various factors, such as additional educational support and parental support groups to improve parenting knowledge and skills. There are also strides being made in education, housing, and social settings to create environments which are accessible and supportive to people with Down syndrome. In most developed countries, since the early twentieth century many people with Down syndrome were housed in institutions or colonies and excluded from society. However, since the early 1960s parents and their organisations (such as MENCAP), educators and other professionals have generally advocated a policy of inclusion, bringing people with any form of mental or physical disability into general society as much as possible. In many countries, people with Down syndrome are educated in the normal school system; there are increasingly higher-quality opportunities to move from special (segregated) education to regular education settings.

Despite these changes, the additional support needs of people with Down syndrome can still pose a challenge to parents and families. Although living with family is preferable to institutionalisation, people with Down syndrome often encounter patronizing attitudes and discrimination in the wider community.

The first World Down Syndrome Day was held on 21 March 2006. The day and month were chosen to correspond with 21 and trisomy respectively. It was proclaimed by European Down Syndrome Association during their European congress in Palma de Mallorca (febr. 2005). In the United States, the National Down Syndrome Society observes Down Syndrome Month every October as "a forum for dispelling stereotypes, providing accurate information, and raising awareness of the potential of individuals with Down syndrome." In South Africa, Down Syndrome Awareness Day is held every October 20. Organisations such as Special Olympics Hawaii provide year-round sports training for individuals with intellectual disabilities such as down syndrome.

History

English physician John Langdon Down first characterized Down syndrome as a distinct form of mental disability in 1862, and in a more widely published report in 1866. Due to his perception that children with Down syndrome shared physical facial similarities (epicanthal folds) with those of Blumenbach's Mongolian race, Down used terms derived from prevailing ethnic theory.

By the 20th century, Down Syndome had become the most recognizable form of mental disability. Most individuals with Down syndrome were institutionalized, few of the associated medical problems were treated, and most died in infancy or early adult life. With the rise of the eugenics movement, 33 of the (then) 48 U.S. states and several countries began programs of forced sterilization of individuals with Down syndrome and comparable degrees of disability. The ultimate expression of this type of public policy was the so called euthanasia program "Action T-4" in Nazi Germany, a program of systematic murder. Court challenges, scientific advances and public revulsion led to discontinuation or repeal of such sterilisation programs during the decades after World War II.

Until the middle of the 20th century, the cause of Down syndrome remained unknown. However, the presence in all races, the association with older maternal age, and the rarity of recurrence had been noticed. Standard medical texts assumed it was caused by a combination of inheritable factors which had not been identified. Other theories focused on injuries sustained during birth.

With the discovery of karyotype techniques in the 1950s, it became possible to identify abnormalities of chromosomal number or shape. In 1959, Jérôme Lejeune discovered that Down syndrome resulted from an extra chromosome. The extra chromosome was subsequently labeled as the 21st, and the condition as trisomy 21.

In 1961, nineteen geneticists wrote to the editor of The Lancet suggesting that Mongolian idiocy had "misleading connotations," had become "an embarrassing term," and should be changed. The Lancet supported Down's Syndrome. The World Health Organization (WHO) officially dropped references to mongolism in 1965 after a request by the Mongolian delegate. However, almost 40 years later, the term ‘mongolism’ still appears in leading medical texts such as Review of Medical Physiology, 22nd Edition, 2005, by Professor William Ganong and General and Systematic Pathology, 4th Edition, 2004, edited by Professor Sir James Underwood.

In 1975, the United States National Institutes of Health convened a conference to standardize the nomenclature of malformations. They recommended eliminating the possessive form: "The possessive use of an eponym should be discontinued, since the author neither had nor owned the disorder." Although both the possessive and non-possessive forms are used in the general population, Down syndrome is the accepted term among professionals in the USA, Canada and other countries; Down's syndrome is still used in the United Kingdom and other areas.