A syndrome may have multiple causes. What causes Down syndrome is well-known, having been discovered by Dr Jerome Lejeune in 1959. He first discovered that the cause is related to the 21st chromosome and the existence of some level of extra genetic material from that chromosome. It is important to note that, while we know the cause, we do not know "why".
There are currently 3 known scenarios related to the 21st chromosome which lead to Down syndrome.
This the most common cause of Down syndrome. Trisomy 21, or T21, is the existence of an extra, complete or partial, copy of the 21st chromosome in every cell of the body. Instead of the usual 46 chromosomes, a person with Trisomy 21 has 47 chromosomes. Trisomy 21 is completely spontaneous, although there are risk factors, including maternal and paternal age. It accounts for 95% of Down syndrome cases.
A translocation involves the long arm of the 21st chromosome attaching to the long arm of another chromosome, usually 13,14,15,21, or 22. Typically, this results in the loss of genetic material, leaving 45 chromosomes. Translocation is typically familial and accounts for 2%-3% of Down syndrome cases.
Mosaic is similar to Trisomy 21, except the extra chromosome is not present in all cells. Depending on which cells are affected, a person with mosaic trisomy 21 may not have Down syndrome. In fact, there are many people with mosaic trisomy 21 and have no idea. It accounts for 1%-2% of Down syndrome cases.