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Genetics Home Reference: your guide to understanding genetic conditions
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Prader-Willi syndrome

Reviewed June 2014

What is 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, 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 outbursts, stubbornness, and compulsive behavior such as picking at the skin. Sleep abnormalities can also occur. Additional features of this condition include distinctive facial features such as a narrow forehead, almond-shaped eyes, and a triangular mouth; 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).

How common is Prader-Willi syndrome?

Prader-Willi syndrome affects an estimated 1 in 10,000 to 30,000 people worldwide.

What are the genetic changes related to Prader-Willi syndrome?

Prader-Willi syndrome is caused by the loss of function of genes in a particular 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.

Most cases of Prader-Willi syndrome (about 70 percent) occur when a segment of the paternal chromosome 15 is deleted in each cell. People with this chromosomal change are missing certain critical genes in this region because the genes on the paternal copy have been deleted, and the genes on the maternal copy are turned off (inactive). 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.

It appears likely that the characteristic features of Prader-Willi syndrome result from the loss of function of several genes on chromosome 15. Among these are genes that provide instructions for making molecules called small nucleolar RNAs (snoRNAs). These molecules have a variety of functions, including helping to regulate other types of RNA molecules. (RNA molecules play essential roles in producing proteins and in other cell activities.) Studies suggest that the loss of a particular group of snoRNA genes, known as the SNORD116 cluster, may play a major role in causing the signs and symptoms of Prader-Willi syndrome. However, it is unknown how a missing SNORD116 cluster could contribute to intellectual disability, behavioral problems, and the physical features of the disorder.

In some people with Prader-Willi syndrome, the loss of a gene called OCA2 is associated with unusually fair skin and light-colored hair. The OCA2 gene is located on the segment of chromosome 15 that is often deleted in people with this disorder. However, loss of the OCA2 gene does not cause the other signs and symptoms of Prader-Willi syndrome. The protein produced from this gene helps determine the coloring (pigmentation) of the skin, hair, and eyes.

Researchers are studying other genes on chromosome 15 that may also be related to the major signs and symptoms of this condition.

Related Chromosome(s)

Changes involving this chromosome are associated with Prader-Willi syndrome.

  • chromosome 15

Related Gene(s)

Changes in this gene are associated with Prader-Willi syndrome.

  • OCA2

Can Prader-Willi syndrome be inherited?

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 change that abnormally inactivates genes on the paternal chromosome 15 to be passed from one generation to the next.

Where can I find information about diagnosis or management of Prader-Willi syndrome?

These resources address the diagnosis or management of Prader-Willi syndrome and may include treatment providers.

  • Gene Review: Prader-Willi Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1330)
  • Genetic Testing Registry: Prader-Willi syndrome (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0032897)
  • MedlinePlus Encyclopedia: Hypotonia (http://www.nlm.nih.gov/medlineplus/ency/article/003298.htm)
  • MedlinePlus Encyclopedia: Prader-Willi Syndrome (http://www.nlm.nih.gov/medlineplus/ency/article/001605.htm)

You might also find information on the diagnosis or management of Prader-Willi syndrome in Educational resources (http://www.ghr.nlm.nih.gov/condition/prader-willi-syndrome/show/Educational+resources) and Patient support (http://www.ghr.nlm.nih.gov/condition/prader-willi-syndrome/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Prader-Willi syndrome?

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

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

What other names do people use for Prader-Willi syndrome?

  • Prader-Labhart-Willi syndrome
  • PWS
  • Willi-Prader syndrome

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Prader-Willi syndrome?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/GARD/).

What glossary definitions help with understanding Prader-Willi syndrome?

cell ; chromosome ; chronic ; contiguous ; contiguous gene syndrome ; deletion ; diabetes ; diabetes mellitus ; disabilities ; disability ; embryonic ; gene ; genitals ; His ; hyperphagia ; hypogonadism ; hypotonia ; imprinting ; infertile ; inherit ; inherited ; maternal ; muscle tone ; mutation ; overeating ; pigmentation ; protein ; puberty ; rearrangement ; reproductive cells ; RNA ; short stature ; sperm ; stature ; syndrome ; translocation ; uniparental disomy

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.ghr.nlm.nih.gov/glossary).

References

  • Bittel DC, Butler MG. Prader-Willi syndrome: clinical genetics, cytogenetics and molecular biology. Expert Rev Mol Med. 2005 Jul 25;7(14):1-20. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16038620?dopt=Abstract)
  • Cassidy SB, Driscoll DJ. Prader-Willi syndrome. Eur J Hum Genet. 2009 Jan;17(1):3-13. doi: 10.1038/ejhg.2008.165. Epub 2008 Sep 10. (http://www.ncbi.nlm.nih.gov/pubmed/18781185?dopt=Abstract)
  • Cassidy SB, Schwartz S, Miller JL, Driscoll DJ. Prader-Willi syndrome. Genet Med. 2012 Jan;14(1):10-26. doi: 10.1038/gim.0b013e31822bead0. Epub 2011 Sep 26. Review. (http://www.ncbi.nlm.nih.gov/pubmed/22237428?dopt=Abstract)
  • Chen C, Visootsak J, Dills S, Graham JM Jr. Prader-Willi syndrome: an update and review for the primary pediatrician. Clin Pediatr (Phila). 2007 Sep;46(7):580-91. Epub 2007 May 23. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17522286?dopt=Abstract)
  • Gene Review: Prader-Willi Syndrome (http://www.ncbi.nlm.nih.gov/books/NBK1330)
  • Goldstone AP, Holland AJ, Hauffa BP, Hokken-Koelega AC, Tauber M; speakers contributors at the Second Expert Meeting of the Comprehensive Care of Patients with PWS. Recommendations for the diagnosis and management of Prader-Willi syndrome. J Clin Endocrinol Metab. 2008 Nov;93(11):4183-97. doi: 10.1210/jc.2008-0649. Epub 2008 Aug 12. Erratum in: J Clin Endocrinol Metab. 2010 Dec;95(12):5465. (http://www.ncbi.nlm.nih.gov/pubmed/18697869?dopt=Abstract)
  • Gunay-Aygun M, Schwartz S, Heeger S, O'Riordan MA, Cassidy SB. The changing purpose of Prader-Willi syndrome clinical diagnostic criteria and proposed revised criteria. Pediatrics. 2001 Nov;108(5):E92. (http://www.ncbi.nlm.nih.gov/pubmed/11694676?dopt=Abstract)
  • Lee S, Wevrick R. Identification of novel imprinted transcripts in the Prader-Willi syndrome and Angelman syndrome deletion region: further evidence for regional imprinting control. Am J Hum Genet. 2000 Mar;66(3):848-58. (http://www.ncbi.nlm.nih.gov/pubmed/10712201?dopt=Abstract)
  • Oiglane-Shlik E, Zordania R, Varendi H, Antson A, Mägi ML, Tasa G, Bartsch O, Talvik T, Ounap K. The neonatal phenotype of Prader-Willi syndrome. Am J Med Genet A. 2006 Jun 1;140(11):1241-4. (http://www.ncbi.nlm.nih.gov/pubmed/16642508?dopt=Abstract)
  • Wattendorf DJ, Muenke M. Prader-Willi syndrome. Am Fam Physician. 2005 Sep 1;72(5):827-30. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16156341?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: June 2014
Published: November 24, 2014