The Genetics of Down Syndrome - Trisomy 21

Down syndrome is a genetic disorder caused by extra genetic material (DNA) (ie, presence of an extra 21st chromosome). Chromosomes, which are microscopic thread-like structures that are present in every cell of the body except red blood cells, carry genes. Genes are necessary for development. Human cells normally have 46 chromosomes that can be arranged in 23 pairs. One set of 23 chromosomes comes from the mother (egg cell or ovum) and the other half of the 23 pairs comes from the father (sperm cell).

Trisomy 21

In Down syndrome, 95% of all cases are caused by either the sperm or the egg cell having two 21st chromosomes instead of one, so the resulting fertilized egg has three 21st chromosomes. Hence the scientific name, trisomy 21. Recent research has shown that in these cases, approximately 90% of the time the abnormal cells are the eggs. The cause of the extra chromosome isn't known, but there is definitely connection with the mother's age.

Robertsonian translocation and partial trisomy 21

A different kind of genetic error occurs in 3-4% of cases of Down syndrome. In this case, the genetic material (genes carried on chromosomes) is rearranged so that some of the 13th, 14th, or 15th chromosome is replaced by an extra copy of genetic material from the 21st chromosome. The overall number of chromosomes remains normal (46 chromosomes in 23 pairs), but there are 3 copies of the 21st chromosome material. Sometimes the extra genetic material only comes from part of the long arm of the 21st chromosome (21q), and this is called partial trisomy 21.

Mosaicism and trisomy 21

Mosaicism causes the remaining cases of Down syndrome. In these cases, people have a mixture of cells (cell lines). Some cells have a normal set of chromosomes, and other cells have trisomy 21. In cellular mosaicism, the mixture is seen in different cells of the same type. In tissue mosaicism, one set of cells, such as all blood cells, may have normal chromosomes, and another type, such as all skin cells, may have trisomy 21.