What Causes Down Syndrome

Down syndrome is usually caused by an error in cell division called non-disjunction. However, two other types of chromosomal abnormalities, mosaicism and translocation, are also implicated in Down syndrome - although to a much lesser extent. Regardless of the type of Down syndrome which a person may have, all people with Down syndrome have an extra, critical portion of the number 21 chromosome present in all, or some, of their cells. This additional genetic material alters the course of development and causes the characteristics associated with the syndrome.


Nondisjunction is a faulty cell division, which results in an embryo with three number 21 chromosomes instead of two. Prior to, or at, conception, a pair of number 21 chromosomes, in either the sperm or the egg, fail to separate. As the embryo develops, the extra chromosome is replicated in every cell of the body. This faulty cell division is responsible for 95 percent of all cases of Down syndrome. Why nondisjunction occurs is currently unknown, although it does seem to be related to advancing maternal age. Many people are surprised to find out that 80 percent of children born with Down syndrome are born to women under 35 years of age. This is because younger women have higher fertility rates. It does not contradict the fact that the incidence of births of children with Down syndrome increases with the age of the mother. Although nondisjunction can be of paternal origin, this occurs less frequently. Because this error in cell division is often present in the egg prior to conception, and women are born with their complete store of eggs, it has been postulated that some environmental factors may be implicated in nondisjunction. However, despite years of research, the cause (or causes) of nondisjunction, is still unknown. There seems to be no connection between any type of Down syndrome and parents' activities before or during pregnancy.


Mosaicism occurs when nondisjunction of the 21st chromosome takes place in one of the initial cell divisions after fertilization. When this occurs, there is a mixture of two types of cells, some containing 46 chromosomes and some containing 47. Those cells with 47 chromosomes contain an extra 21st chromosome. Because of the "mosaic" pattern of the cells, the term mosaicism is used. Mosaicism is rare, being responsible for only one to two percent of all cases of Down syndrome. Some research has shown that individuals with mosaic Down syndrome are less affected than those with trisomy 21; however, broad generalizations are not possible due to the wide range of abilities that people with Down syndrome possess.


Translocation is a different type of chromosomal problem and occurs in only three to four percent of people with Down syndrome. Translocation occurs when part of the number 21 chromosome breaks off during cell division and attaches to another chromosome. While the total number of chromosomes in the cells remains 46, the presence of an extra part of the number 21 chromosome causes the features of Down syndrome. As with nondisjunction trisomy 21, translocation occurs either prior to or at conception. Unlike nondisjunction, maternal age is not linked to the risk of translocation. Most cases are sporadic, chance events. However, in about one-third of cases, one parent is a carrier of a translocated chromosome. For this reason, the risk of recurrence for translocation is higher than that of nondisjunction. Genetic counseling can be sought to determine the origin of the translocation.

Source: National Down Syndrome Society