Trisomy 17 mosaicism occurs due to a random event during the formation of the reproductive cells (egg and sperm) or after fertilization has taken place. An error in cell division (called nondisjunction) may cause some eggs or sperm to have an abnormal number of chromosomes. If an egg or sperm with an extra chromosome 17 contributes to the genetic makeup of an embryo, the embryo will have an extra copy of chromosome 17 in each cell. As the embryo grows and divides, an attempt may be made to correct the mistake by eliminating one extra chromosome 17. In individuals with trisomy 17 mosaicism, this attempt may be partly successful, leaving some cells with an extra chromosome 17 and some cells with the extra chromosome deleted (the usual chromosome number). This correction process is called trisomy rescue.

In other cases, the egg and sperm may have a normal number of chromosomes, but an error of cell division (nondisjunction) occurs when the fertilized egg is growing and dividing. If an error occurs during one of the divisions, it can cause some cells to have an abnormal number of chromosomes. In people affected by trisomy 17 mosaicism, some of the body's cells have the usual two copies of chromosome 17, and other cells have three copies of this chromosome (trisomy). The percentage of cells with trisomy 17 and which parts of the body are affected vary from person to person. This leads to variability in the range and severity of symptoms.