Prader-Willi syndrome

Prader-Willi syndrome is a complex genetic condition that affects many parts of the body. In infancy, this condition is characterized by weak muscle tone (hypotonia), feeding difficulties, poor growth, and delayed development. Beginning in childhood, affected individuals develop an insatiable appetite and chronic overeating (hyperphagia). As a result, most experience rapid weight gain leading to obesity. People with Prader-Willi syndrome typically have intellectual impairment or learning disabilities and behavioral problems. Many people with this disorder also have distinctive facial features and short stature. The genitals in both males and females are underdeveloped, and most affected individuals are unable to conceive children (infertile). Additionally, some people with Prader-Willi syndrome have unusually fair skin and light-colored hair.

Prader-Willi syndrome affects an estimated 1 in 10,000 to 25,000 people.

Prader-Willi syndrome is related to chromosome 15.

The OCA2 gene is associated with Prader-Willi syndrome.

Prader-Willi syndrome is caused by the loss of active genes in a specific region of chromosome 15. People normally inherit one copy of this chromosome from each parent. Some genes are active only on the copy that is inherited from a person's father (the paternal copy). This parent-specific gene activation is called genomic imprinting. Prader-Willi syndrome occurs when the region of the paternal chromosome 15 containing these genes is missing.

Researchers are working to identify genes on chromosome 15 that are responsible for the characteristic features of Prader-Willi syndrome. They have not definitively connected many genes with specific signs and symptoms. Researchers have determined, however, that a deletion of the OCA2 gene on chromosome 15 is associated with unusually fair skin and light-colored hair in some affected individuals. The protein produced from this gene helps determine the coloring (pigmentation) of the skin, hair, and eyes.

Most cases of Prader-Willi syndrome (about 70 percent) occur when a segment of the paternal chromosome 15 is deleted in each cell. In another 25 percent of cases, a person with Prader-Willi syndrome has two copies of chromosome 15 inherited from his or her mother (maternal copies) instead of one copy from each parent. This phenomenon is called maternal uniparental disomy. Rarely, Prader-Willi syndrome can also be caused by a chromosomal rearrangement called a translocation, or by a mutation or other defect that abnormally inactivates genes on the paternal chromosome 15. Each of these genetic changes results in a loss of gene function in a critical region of chromosome 15.

Read more about the OCA2 gene and chromosome 15.

Most cases of Prader-Willi syndrome are not inherited, particularly those caused by a deletion in the paternal chromosome 15 or by maternal uniparental disomy. These genetic changes occur as random events during the formation of reproductive cells or in early fetal development. Affected people typically have no history of the disorder in their family.

Rarely, a genetic change responsible for Prader-Willi syndrome can be inherited. For example, it is possible for a genetic defect that abnormally inactivates genes on the paternal chromosome 15 to be passed from one generation to the next.