Causes of Down Syndrome

Down syndrome results from cell division errors, either prior to or at conception. Trisomy 21 is caused by nondisjunction during cell division (condition in which a pair of chromosomes does not properly separate).

Normally, all cells have 23 pairs of matching chromosomes, 46 chromosomes in all. When egg and sperm cells divide in two, they distribute their 46 chromosomes equally—one chromosome from each pair moves to one of the resulting cells, forming two cells with 23 single chromosomes each. At fertilization, the resulting embryo receives 23 chromosomes each from the egg and sperm cells, bringing the total to 46 (23 pairs).

When nondisjunction occurs, chromosome 21 is not equally distributed when the egg or sperm cell divides, leaving one of the resulting cells with two copies of chromosome 21, instead of one. If this is the egg or sperm cell that gets fertilized, the abnormal cell contributes two copies of chromosome 21 to the embryo, which then has three copies (also including one copy from the normal egg or sperm cell). As the embryo grows, the extra copy becomes part of every cell thereafter.

Mosaic Down syndrome develops in a similar way, but nondisjunction occurs after fertilization, when the embryo is undergoing its own first series of cell divisions. This is why a person with mosaic Down syndrome has the correct number of chromosomes in some cells and the extra chromosome 21 in others.

Translocation Down syndrome is caused by abnormal cell division as well. In this case, when the cell divides, a piece of chromosome 21 breaks off and attaches itself to another chromosome. Even though the resulting cells have the correct number of chromosomes, the extra genetic material from chromosome 21 causes symptoms of Down syndrome.

Medical professionals know Down syndrome occurs because of the duplicated genetic material from chromosome 21, but they do not know why abnormal cell divisions occur.

Down Syndrome Risk Factors

The age of the mother is an important consideration in assessing Down syndrome risk. As a woman gets older, her eggs are more likely to divide abnormally. At age 25, the risk for Down syndrome is 1 in 1,250 births. This risk increases to 1 in 385 at age 35 and jumps to 1 in 30 at age 45. However, 80 percent of babies with Down syndrome are born to mothers who are younger than age 35. The reason for this is that women under the age of 35 have a higher rate of giving birth.

Women who have a child with Down syndrome are more likely to have another baby affected with the condition. Also, mothers who have Down syndrome themselves are 50 percent more likely to give birth to a child with Down syndrome.

Parents can pass down a chromosomal abnormality called balanced translocation, which contributes to Translocation Down syndrome. In this instance, the parent does not have signs of Down syndrome, but has genetic material "balanced" between chromosome 21 and another chromosome, posing an increased risk for the child if that material attaches to the other chromosome when the cell divides. Not all cases of Translocation Down syndrome occur this way, however.

Publication Review By: Stanley J. Swierzewski, III, M.D.

Published: 27 Aug 2008

Last Modified: 14 Sep 2015