Prader-Willi Syndrome

*Prader-Willi syndrome facts by John P. Cunha, DO, FACOEP

• Prader-Willi syndrome (also called Prader-Labhart-Willi syndrome, or PWS) is a complex genetic condition. Infants have weak muscle tone (hypotonia), feeding difficulties, poor growth, and delayed development. Beginning in childhood, individuals may develop an insatiable appetite, which leads to chronic overeating (hyperphagia), obesity, and type 2 diabetes mellitus.
• Prader-Willi syndrome is caused by the loss of genes in a specific region of chromosome 15, though it is not usually inherited.
• People with Prader-Willi syndrome typically have mild to moderate intellectual impairment and learning disabilities. Behavioral problems such as temper tantrums, stubbornness, and compulsive behavior are common. Many have sleep abnormalities.
• Individuals with PWS have distinctive facial features, short stature, and small hands and feet. Some have fair skin and light-colored hair. Both males and females have underdeveloped genitals. Puberty is delayed or incomplete, and most are infertile.

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, some affected individuals develop an insatiable appetite, which leads to chronic overeating (hyperphagia) and obesity. Some people with Prader-Willi syndrome, particularly those with obesity, also develop type 2 diabetes mellitus (the most common form of diabetes).

People with Prader-Willi syndrome typically have mild to moderate intellectual impairment and learning disabilities. Behavioral problems are common, including temper tantrums, stubbornness, and compulsive behavior. Many affected individuals also have sleep abnormalities.

Additional features of this condition include distinctive facial features, short stature, and small hands and feet. Some people with Prader-Willi syndrome have unusually fair skin and light-colored hair. Both affected males and affected females have underdeveloped genitals. Puberty is delayed or incomplete, and most affected individuals are unable to have children (infertile).

Prader-Willi syndrome is caused by the loss of genes in a specific region of chromosome 15. People normally inherit one copy of this chromosome from each parent. Some genes are turned on (active) only on the copy that is inherited from a person's father (the paternal copy). This parent-specific gene activation is caused by a phenomenon 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 determined 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. Researchers have not definitively connected any other genes with specific signs and symptoms of Prader-Willi syndrome.

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 turns off (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.

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 (eggs and sperm) or in early embryonic 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.

These resources address treatment or management of Prader-Willi syndrome or some of its symptoms.

• DNA Test
• Gene Review: Prader-Willi Syndrome
• MedTerms: Hypotonia
• MedlinePlus Encyclopedia: Prader-Willi syndrome

You might also find information on treatment of Prader-Willi syndrome in Educational resources and Patient support.

You may find the following resources about Prader-Willi syndrome helpful. These materials are written for the general public.

• NIH Publications - National Institutes of Health (2 links)
• MedlinePlus - Health information (4 links)
• Educational resources - Information pages (7 links)
• Patient support - For patients and families (4 links)

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

• ClinicalTrials.gov - Linking patients to medical research
• PubMed - Recent literature Online Books - Medical and science texts Scriver's

• Prader-Labhart-Willi syndrome
• PWS

• See How can I find a genetics professional in my area? 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 the number of chromosomes affect health and development?
• Are chromosomal disorders inherited?
• What are genomic imprinting and uniparental disomy?

These links provide additional genetics resources that may be useful.

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