Three genetic variations can cause Down syndrome. In most cases, approximately 92% of the time, Down syndrome is caused by the presence of an extra chromosome 21 in all cells of the individual. In such cases, the extra chromosome originates in the development of either the egg or the sperm. Consequently, when the egg and sperm unite to form the fertilized egg, three--rather than two--chromosomes 21 are present. As the embryo develops, the extra chromosome is repeated in every cell. This condition, in which three copies of chromosome 21 are present in all cells of the individual, is called trisomy 21.
In approximately 2-4% of cases, Down syndrome is due to mosaic trisomy 21. This situation is similar to simple trisomy 21, but, in this instance, the extra chromosome 21 is present in some, but not all, cells of the individual. For example, the fertilized egg may have the right number of chromosomes, but, due to an error in chromosome division early in embryonic development, some cells acquire an extra chromosome 21. Thus, an individual with Down syndrome due to mosaic trisomy 21 will typically have 46 chromosomes in some cells, but will have 47 chromosomes (including an extra chromosome 21) in others. In this situation, the range of the physical problems may vary, depending on the proportion of cells that carry the additional chromosome 21.
In trisomy 21 and mosaic trisomy 21, Down syndrome occurs because some or all of the cells have 47 chromosomes, including three chromosomes 21. However, approximately 3-4% of individuals with Down syndrome have cells containing 46 chromosomes, but still have the features associated with Down syndrome. How can this be? In such cases, material from one chromosome 21 gets stuck or translocated onto another chromosome, either prior to or at conception. In such situations, cells from individuals with Down syndrome have two normal chromosomes 21, but also have additional chromosome 21 material on the translocated chromosome. Thus, there is still too much material from chromosome 21, resulting in the features associated with Down syndrome. In such situations, the individual with Down syndrome is said to have translocation trisomy 21.