Édouard Séguin described it as separate from cretinism in 1844. By the 20th century, Down syndrome had become the most recognizable form of mental disability. In antiquity, many infants with disabilities were either killed or abandoned. In June 2020, the earliest incidence of Down syndrome was found in genomic evidence from an infant that was buried before 3200 BC at Poulnabrone dolmen in Ireland. Researchers believe that a number of historical pieces of art portray Down syndrome, including pottery from the pre-Columbian Tumaco-La Tolita culture in present-day Colombia and Ecuador, and the 16th-century painting The Adoration of the Christ Child.In the 20th century, many individuals with Down syndrome were institutionalized, few of the associated medical problems were treated, and most people died in infancy or early adulthood. 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. Action T4 in Nazi Germany made public policy of a program of systematic involuntary euthanization.With the discovery of karyotype techniques in the 1950s it became possible to identify abnormalities of chromosomal number or shape. In 1959 Jérôme Lejeune reported the discovery that Down syndrome resulted from an extra chromosome. However, Lejeunes claim to the discovery has been disputed, and in 2014 the Scientific Council of the French Federation of Human Genetics unanimously awarded its Grand Prize to his colleague Marthe Gautier for her role in this discovery.
Translocation
The extra chromosome 21 material may also occur due to a Robertsonian translocation in 2–4% of cases. In this situation, the long arm of chromosome 21 is attached to another chromosome, often chromosome 14. In a male affected with Down syndrome, it results in a karyotype of 46XY,t(14q21q). This may be a new mutation or previously present in one of the parents. The parent with such a translocation is usually normal physically and mentally; however, during production of egg or sperm cells, a higher chance of creating reproductive cells with extra chromosome 21 material exists. This results in a 15% chance of having a child with Down syndrome when the mother is affected and a less than 5% probability if the father is affected. The probability of this type of Down syndrome is not related to the mothers age. Some children without Down syndrome may inherit the translocation and have a higher probability of having children of their own with Down syndrome. In this case it is sometimes known as familial Down syndrome. Mechanism
The extra genetic material present in Down syndrome results in overexpression of a portion of the 310 genes located on chromosome 21. This overexpression has been estimated at 50%, due to the third copy of the chromosome present. Some research has suggested the Down syndrome critical region is located at bands 21q22.1–q22.3, with this area including genes for the amyloid precursor protein, superoxide dismutase, and likely the ETS2 proto oncogene. Other research, however, has not confirmed these findings.