The Three Genetic Forms of PWS

Although every case of Prader-Willi syndrome is due to the baby failing to receive active genes from a specific section of the father's chromosome 15, there are three different ways that this can happen:

Paternal deletion - about 70 percent of all cases of PWS;

In the most common form of PWS, part of the chromosome 15 inherited from the child's father-the part containing the PWS imprinted genes-is missing. In some cases, the section that has disappeared (called a "deletion") is large enough to be identified in chromosome studies done with a microscope; in other cases, it is too small but it can be detected with another test called FISH (Fluorescence In Situ Hybridization). Usually a deletion happens for no known reason, and it is not likely to happen again in another pregnancy. There is nothing the father did (or did not do) to cause it and no way to prevent it. In rare cases of extremely tiny (micro) deletions, or when a chromosome change such as a "translocation" caused the PWS genes to be lost, the family could have another child with the same condition. (In a translocation, part of one chromosome is broken off and attached to a different chromosome.) It's especially important for these families to have further testing and genetic counseling.

Maternal uniparental disomy (UPD) - about 25 percent of cases

In this less common form of PWS, the baby inherits both copies of chromosome 15 from one parent-the mother. (Maternal means mother; uniparental means one parent; and disomy means two chromosome bodies). In these cases, the developing baby usually starts out with three copies of chromosome 15 (a condition called trisomy 15) because somehow there was an extra number 15 in the mother's egg. Later, one of the three is lost-the chromosome 15 that came from the father's sperm. The result has the same effect as a deletion: The child does not have the two or more active imprinted genes that must come from the father in order to be "expressed" (to function). Even though there are two complete copies of the mother's chromosome 15, the key genes in the PWS region are imprinted to be turned "off" in the mother's copies. Because the error in this form of PWS starts with an extra chromosome in the mother's egg, and older eggs are more likely to have errors of this type, older mothers are more likely than younger mothers to have a baby with this form of PWS. Even so, it is not likely to happen to a second child in the same family. When a baby inherits two identical chromosome 15s from the mother (two copies of the same one rather than one of each of the mother's own chromosomes), there is a chance of having some additional genetic problems.

Imprinting mutation - less than 5 percent of cases

In very rare cases, the PWS genes on the father's chromosome are present but do not work because the imprinting process that normally switches them to "on" did not do its job. The imprinting process is controlled by a tiny imprinting center on chromosome 15 in the same area as the important genes. When there is a mutation (a change) that affects this tiny control center, imprinting doesn't happen and the PWS genes from the father will not work as they should. A mutation can appear suddenly, or it can be present in the father's chromosome that he got from his mother. If he received the mutation from his mother, the father would not have PWS himself (because it's on his maternal chromosome 15), but he could pass it on to his child. In this case, there is a 50-50 chance that any child he has will receive the chromosome with the mutation instead of the one that's working correctly. Likewise, the father's siblings could carry and pass on the mutation to their children. Further testing and genetic counseling are especially important for families who have a child with this form of PWS.