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

Reviewed October 2011

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. Many affected individuals also have sleep abnormalities. 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.

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/bookshelf/br.fcgi?book=gene&part=pws)
  • Gene Tests: Prader-Willi Syndrome (http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/2149)
  • 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://ghr.nlm.nih.gov/condition/prader-willi-syndrome/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/prader-willi-syndrome/show/Patient+support).

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.

  • MedlinePlus - Health information

    • Encyclopedia: Hypotonia (http://www.nlm.nih.gov/medlineplus/ency/article/003298.htm)
    • Encyclopedia: Prader-Willi syndrome (http://www.nlm.nih.gov/medlineplus/ency/article/001605.htm)
    • Health Topic: Prader-Willi Syndrome (http://www.nlm.nih.gov/medlineplus/praderwillisyndrome.html)
  • Genetic and Rare Diseases Information Center - Information about genetic conditions and rare diseases (http://rarediseases.info.nih.gov/GARD/Disease.aspx?PageID=4&DiseaseID=5575)

  • Additional NIH Resources - National Institutes of Health

    • Eunice Kennedy Shriver National Institute of Child Health and Human Development (http://www.nichd.nih.gov/health/topics/Prader_Willi_Syndrome.cfm)
    • National Center for Biotechnology Information: Genes and Disease (http://www.ncbi.nlm.nih.gov/books/bv.fcgi?call=bv.View..ShowSection&rid=gnd.section.182)

  • Educational resources - Information pages

    • Madisons Foundation (http://www.madisonsfoundation.org/index.php?option=com_mpower&task=disease&diseaseID=80)
    • Orphanet (http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=739)
    • Swedish Information Center for Rare Diseases (http://www.socialstyrelsen.se/rarediseases/prader-willisyndrome)

  • Patient support - For patients and families

    • Angelman, Rett, and Prader-Willi Syndromes Consortium (http://rarediseasesnetwork.epi.usf.edu/arpwsc/)
    • Family Village (http://www.familyvillage.wisc.edu/lib_pws.htm)
    • International Prader-Willi Syndrome Organization (http://www.ipwso.org/)
    • National Organization for Rare Disorders (http://www.rarediseases.org/rare-disease-information/rare-diseases/byID/14/viewAbstract)
    • Prader-Willi Syndrome Association (USA) (http://www.pwsausa.org/)
    • Resource list from the University of Kansas Medical Center (http://www.kumc.edu/gec/support/prader.html)
    • The Foundation for Prader-Willi Research (http://fpwr.org/)

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

  • Gene Reviews - Clinical summary (http://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=pws)
  • Gene Tests - DNA tests ordered by healthcare professionals (http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/clinical_disease_id/2149)
  • ClinicalTrials.gov - Linking patients to medical research (http://clinicaltrials.gov/ct2/results?cond=%22Prader-Willi%20syndrome%22)
  • PubMed - Recent literature (http://www.ncbi.nlm.nih.gov/pubmed?term=(Prader-Willi%20Syndrome%5BMAJR%5D)%20AND%20(Prader-Willi%20syndrome%5BTI%5D)%20AND%20english%5Bla%5D%20AND%20human%5Bmh%5D%20AND%20%22last%20360%20days%22%5Bdp%5D)
  • Online Books - Medical and science texts
    Scriver's Online Metabolic and Molecular Bases of Inherited Disease (OMMBID): Molecular Cytogenetics of Contiguous Gene Syndromes: Mechanisms and Consequences of Gene Dosage Imbalance (http://books.mcgraw-hill.com/getommbid.php?isbn=0071459960&template=ommbid&c=65)
  • OMIM - Genetic disorder catalog (http://omim.org/entry/176270)

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 ; egg ; embryonic ; gene ; genitals ; hyperphagia ; hypogonadism ; hypotonia ; imprinting ; infertile ; learning disability ; maternal ; molecule ; muscle tone ; mutation ; overeating ; pigmentation ; protein ; puberty ; rearrangement ; reproductive cells ; RNA ; short stature ; sign ; sperm ; stature ; symptom ; syndrome ; translocation ; uniparental disomy

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://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)
  • Bittel DC, Kibiryeva N, Talebizadeh Z, Butler MG. Microarray analysis of gene/transcript expression in Prader-Willi syndrome: deletion versus UPD. J Med Genet. 2003 Aug;40(8):568-74. (http://www.ncbi.nlm.nih.gov/pubmed/12920063?dopt=Abstract)
  • Butler MG. Prader-Willi syndrome: current understanding of cause and diagnosis. Am J Med Genet. 1990 Mar;35(3):319-32. (http://www.ncbi.nlm.nih.gov/pubmed/2309779?dopt=Abstract)
  • Cassidy SB, Driscoll DJ. Prader-Willi syndrome. Eur J Hum Genet. 2009 Jan;17(1):3-13. Epub 2008 Sep 10. (http://www.ncbi.nlm.nih.gov/pubmed/18781185?dopt=Abstract)
  • Cassidy SB, Dykens E, Williams CA. Prader-Willi and Angelman syndromes: sister imprinted disorders. Am J Med Genet. 2000 Summer;97(2):136-46. Review. (http://www.ncbi.nlm.nih.gov/pubmed/11180221?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/bookshelf/br.fcgi?book=gene&part=pws)
  • 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. 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)
  • Goldstone AP. Prader-Willi syndrome: advances in genetics, pathophysiology and treatment. Trends Endocrinol Metab. 2004 Jan-Feb;15(1):12-20. Review. (http://www.ncbi.nlm.nih.gov/pubmed/14693421?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)
  • Nativio DG. The genetics, diagnosis, and management of Prader-Willi syndrome. J Pediatr Health Care. 2002 Nov-Dec;16(6):298-303. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12436099?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: October 2011
Published: May 21, 2012