Deletion in the paternally contributed chromosome 15
Seventy percent of the cases of PWS are caused when a piece of material is deleted, or erased, from the paternal chromosome 15. This deletion occurs in a specific region on the q arm of chromosome 15. The piece of chromosomal material that is deleted contains genes that must be present for normal development. These paternal genes must be working normally, because the same genes on the chromosome 15 inherited from the mother are imprinted. When these paternal genes are missing, the brain and other parts of the body do not develop as expected. This is what causes the symptoms associated with PWS.
In 99 percent of the cases of PWS, the deletion is sporadic. This means that it happens randomly, there is not an apparent cause, and the condition is not inherited. If a child has PWS due to a sporadic deletion in the paternal chromosome 15, the chance the parents could have another child with PWS is less than 1 percent. In fewer than 1 percent of the cases of PWS there is a chromosomal rearrangement in the family that causes the deletion. This chromosomal rearrangement is called translocation. If a parent has a translocation the risk of having a child with PWS is higher than 1 percent.
Maternal uniparental disomy
PWS can also develop if a child receives both chromosome 15s from his or her mother. This is seen in approximately 25 percent of the cases of PWS. Maternal uniparental disomy for chromosome 15 leads to PWS because the genes on chromosome 15 that should have been inherited from the father are missing, and the genes on both the chromosome 15s inherited from the mother are imprinted.
PWS caused by maternal uniparental is sporadic. This means that it occurs randomly and there is not an apparent cause. If a child has PWS due to maternal uniparental disomy, the chance the parents could have another child with PWS is less than 1 percent.
Error in imprinting process than renders paternal contribution non-functional
Approximately 2–5 percent of patients with PWS have a change (mutation) in a gene located on the q arm of chromosome 15. This mutation leads to incorrect imprinting. This mutation causes genes inherited from the father to be imprinted or silenced, which should not normally be imprinted. If a child has PWS due to a mutation that changes imprinting, the chance the parents could have another child with PWS is approximately 5 percent.