Down syndrome is the most common birth defect. It was first described in 1866 and is named after John Langdon Down, the doctor who first identified the syndrome. The cause of Down syndrome, also known as trisomy 21, was discovered in 1959.

What causes Down Syndrome?

Down syndrome can be caused by one of three types of abnormal cell division involving chromosome 21. The three genetic variations include:

• Trisomy 21: More than 90 % of Down syndrome cases are caused by trisomy 21. An extra chromosome (chromosome 21) originates in the development of either the sperm or the egg. When the egg and the sperm unite to form the fertilized egg, three (rather than two) chromosomes 21 are present. As the cells divide the extra chromosome is repeated in every cell.
• Mosaic Trisomy 21: This is a rare form (less than 2% of cases) of Down syndrome. While similar to simple trisomy 21, the difference is that the extra chromosome 21 is present in some, but not all cells, of the individual. This type of Down syndrome is caused by abnormal cell division after fertilization. The name comes from a random order of normal and abnormal cells (a mosaic). In cellular mosaicism, the mixture can be seen in different cells of the same type; while with tissue mosaicism, one set of cells may have normal chromosomes and another type may have trisomy 21.
• Translocation Trisomy 21: Sometimes (in 3-4% of cases) part of chromosome 21 becomes attached (translocated) to another chromosome (usually the 13th, 14th or 15th chromosome) before or at conception. The carrier (the one having the translocated chromosome) will have 45 chromosomes instead of 46 but they will have all the genetic material of a person with 46 chromosomes. This is because the extra chromosome 21 material is located on a different chromosome (the translocated one). A carrier will have the extra material but will have only one chromosome 21. The carrier will not exhibit any of the symptoms of Down syndrome because they have the correct amount of genetic material.

For couples who have had one child with Down syndrome due to translocation trisomy 21, there may be an increased likelihood of Down syndrome in future pregnancies. This is because one of the parents may be a balanced carrier of the translocation. The chance of passing the translocation depends on the sex of the parent who carries the rearranged chromosome 21. If the father is the carrier, the risk is about 3 percent, with the mother as the carrier, the risk is about 12 percent.

In all cases of Down syndrome, but especially in cases with translocation trisomy 21, it is important for the parents to have genetic counseling in order to determine their risk.

There are no known behavioral or environmental causes of Down syndrome.