This is the most common form of Down syndrome, accounting for about 95% of all cases. A person with Trisomy 21 has three copies of chromosome 21 (instead of the usual two copies) in every cell of his or her body.

This form of Down syndrome results when a person has an extra copy of chromosome 21 in only a portion of their body's cells. It occurs during cell division in one of two ways. In the first scenario, the original fertilized cell has three copies of chromosome 21, but as it begins to divide, a copy of the cell manages to repair itself. That results in a mixture of mutated cells dividing alongside normal cells to create the baby. In the second scenario, the original cell is a healthy cell, but as it begins to divide, the mutation occurs. Again, this results in a mixture of mutated cells dividing alongside healthy cells to create the baby. Although people with Mosaic Down syndrome do have healthy cells, the end result is basically the same – Down syndrome. They don't have a physical or mental advantage or disadvantage compared to other Down syndrome babies.

This form of Down syndrome occurs when part of chromosome 21 becomes attached (translocated) to another chromosome during the formation of egg and sperm cells, or very early in fetal development. Affected people have two copies of chromosome 21, plus extra material from chromosome 21 attached to another chromosome.