Down syndrome is usually caused by an error in cell division called nondisjunction. 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 a person may have, all people with Down syndrome have an extra, critical portion of chromosome 21 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.
TRISOMY 21 KARYOTYPE (FEMALE)
CHROMOSOME 21 MAP
The indicated region of chromosome 21 appears to be associated with many of the characteristics linked to Down syndrome.
Nondisjunction
Nondisjunction is a faulty cell division that results in an embryo with three copies of chromosome 21 instead of the usual two. Prior to or at conception, a pair of 21st chromosomes in either the sperm or the egg fails to separate. As the embryo develops, the extra chromosome is replicated in every cell of the body.This error in cell division is responsible for 95 percent of all cases of Down syndrome.
NORMAL CELL DIVISION
During fertilization, the 23 chromosomes from the egg and sperm combine. The resulting fertilized egg has 46 chromosomes. During mitosis, the cell replicates itself and divides into two cells with 46
chromosomes in each.
NONDISJUNCTION
Nondisjunction is the failure of the pair of chromosomes to separate during meiosis, which is the process by which egg and sperm cells replicate themselves and divide. Nondisjunction results in both 21st chromosomes being carried to one cell and none to the other.
Why nondisjunction occurs is currently unknown, although research has shown that it increases in frequency as a woman ages. However, 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 occurs because younger women have higher birth rates. It does not contradict the fact that the incidence of births of children with Down syndrome dramatically increases with the age of the mother. Once a woman has given birth to a baby with Down syndrome, it is estimated that the risk of having a second child with Down syndrome is about one in 100. However, the age of the mother may also be a risk factor.
INCIDENCE OF DOWN SYNDROME AND MATERNAL AGE
Maternal Age = Incidence of Down Syndrome
20 = 1 in 2000
24 = 1 in 1300
27 = 1 in 1050
30 = 1 in 900
33 = 1 in 600
36 = 1 in 300
40 = 1 in 100
42 = 1 in 70
45 = 1 in 30
47 = 1 in 20
48 = 1 in 15
49 = 1 in 10
Although nondisjunction can be of paternal origin, it is much less common. It has been suggested that environmental factors may cause nondisjunction. However, despite years of research, the cause (or causes) of nondisjunction is still unknown. There is no scientific evidence that environmental factors or the parents’ activities before or during pregnancy have an effect on any of the three types of Down syndrome.
Mosaicism
Mosaicism occurs when nondisjunction of chromosome 21 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 chromosome 21. Because of the “mosaic” pattern of the cells, the term mosaicism is used. Mosaicism is rare, responsible for only one to two percent of all cases of Down syndrome.
Research has indicated that individuals with mosaic Down syndrome may be less affected by the physical and mental characteristics of Down syndrome than those with nondisjunction or translocation; however, broad generalizations are not possible due to the wide range of abilities that people with Down syndrome possess.
Mosaicism occurs after the fertilized egg begins to divide normally.
Nondisjunction occurs in one cell line resulting in an individual with a combination of both typical and Trisomy 21 cell lines.
Translocation
Translocation accounts for only three to four percent of cases of Down syndrome. In translocation, part of chromosome 21 breaks off during cell division and attaches to another chromosome. While the total number of chromosomes in the cells remain 46, the presence of an extra part of chromosome 21 causes the characteristics of Down syndrome. As with nondisjunction, translocation occurs either prior to or at conception. But, unlike nondisjunction,
maternal age is not linked to the risk of translocation. Most cases are sporadic, chance events. However, in about one third of translocation incidents, one parent is a carrier of a translocated chromosome. For this reason, the risk of recurrence of translocation in a subsequent child is higher than that of nondisjunction. Genetic counseling can determine the origin of translocation.
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