Prader-Willi syndrome

Prader-Willi syndrome is a complex genetic condition that affects many parts of the body. The condition is characterized in infancy by weak muscle tone (hypotonia), feeding difficulties, poor growth, and delayed development. Beginning in childhood, features of the disorder include excessive eating (hyperphagia), obesity, short stature, mental retardation or learning disabilities, and behavioral problems. Some affected individuals also have unusually fair skin and light-colored hair.

Prader-Willi syndrome affects an estimated 1 in 10,000 to 22,000 people.

Prader-Willi syndrome is a chromosomal condition related to chromosome 15.

The OCA2 gene is associated with Prader-Willi syndrome.

This condition is caused by the loss of active genes in a specific region of chromosome 15. People normally have two copies of this chromosome in each cell, one copy from each parent. Some genes on this chromosome, however, are only active when they are inherited from a person's father (the paternal copies). Prader-Willi syndrome occurs when the region of paternal chromosome 15 containing these genes is missing.

Researchers are not yet certain which genes on chromosome 15 are responsible for Prader-Willi syndrome or why a lack of those genes leads to the characteristic features of the condition. They have determined, however, that a loss of the OCA2 gene is responsible for the unusually fair skin and light-colored hair in some affected individuals.

Most cases of Prader-Willi syndrome (about 70 percent) occur when a segment of paternal chromosome 15 is deleted. In about 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 change that abnormally inactivates genes on paternal chromosome 15. Each of these genetic changes results in a loss of gene function in a critical region of chromosome 15.

Most cases of Prader-Willi syndrome are not inherited, particularly those caused by a deletion in 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 mutation that abnormally inactivates genes on paternal chromosome 15 to be passed from one generation to the next.

You may find the following resources about Prader-Willi syndrome helpful.

• MedlinePlus - Health Information (2 links)
• Genes and Disease - Genetic disorder summaries
• Educational resources - Information pages (3 links)
• Patient support - For patients and families (5 links)

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

• Gene Reviews - Clinical summary
• Gene Tests - DNA tests ordered by healthcare professionals
• ClinicalTrials.gov - Linking patients to medical research
• PubMed - Recent literature

See How are genetic conditions and genes named? in the Handbook.

The Handbook provides basic information about genetics in clear language.

• What does it mean if a disorder seems to run in my family?
• What is a chromosome?
• Can changes in chromosomes cause disorders?
• Are chromosomal disorders inherited?

These links provide additional genetics resources that may be useful.

• Genetics and health
• Resources for Patients and Families
• Resources for Health Professionals

chromosome ; contiguous gene syndrome ; critical region ; deletion ; excessive eating ; gene ; hyperphagia ; imprinting ; learning disability ; maternal ; mental retardation ; muscle tone ; mutation ; rearrangement ; stature ; translocation ; uniparental disomy

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.