Prader-Willi syndrome

Prader-Willi syndrome is a genetic disorderin which seven genes (or some subset thereof) on chromosome15 are missing or unexpressed (chromosome 15q partial deletion). It was identified in 1956by Andrea Prader, Heinrich Willi, Alexis Labhart, and Guido Fanconi of Switzerland.

Symptoms

Prader-Willi syndrome (PWS) is characterized by:

• Severe hypotoniaand feeding difficulties in early infancy.
• Excessive eating and gradual development of morbid obesityin later infancy or early childhood, unless externally controlled.
• Mental retardationand distinctive behavioral problemsin all patients.
• Hypogonadismis present in both males and females.
• Short statureis common.

Diagnosis/testing

Accurate consensus clinical diagnostic criteria exist, but the mainstay of diagnosis is genetic testing, specifically DNA-based methylation testing to detect the absence of the paternally contributed Prader-Willi syndrome/Angelman syndrome (PWS/AS) region on chromosome15q11.2-q13. Such testing detects over 99% of patients. Methylation-specific testing is important to confirm the diagnosis of PWS in all individuals, but especially those who are too young to manifest sufficient features to make the diagnosis on clinical grounds or in those individuals who have atypical findings.

Treatment

In 2000, the US FDAapproved the use of growth hormone treatmentfor treating symptoms related to PWS. It appears that HGH has some positive effects in reducing both the hypotonia and hyperphagia (excessive eating) aspects of the disease.

Genetics

PWS is caused by absence of the paternally derived PWS/AS region of chromosome 15 by one of several genetic mechanisms, including uniparental disomy, imprintingmutations, chromosome translocations, and gene deletions. The genesresponsible for Prader-Willi syndrome are expressed only on the paternal chromosome. (Interestingly, a deletion on the maternal chromosome causes Angelman syndrome.) This is the first known instance of imprintingin humans.

The risk to the sibling of an affected child of having PWS depends upon the genetic mechanism which caused the disorder. The risk to siblings is <1% if the affected child has a gene deletion or uniparental disomy, up to 50% if the affected child has a mutation of the imprinting control center, and up to 25% if a parental chromosomal translocation is present. Prenatal testingis possible for any of the known genetic mechanisms.

References

• Prader A, Labhart A, Willi H. Ein Syndrom von Adipositas, Kleinwuchs, Kryptorchismus und Oligophrenie nach Myatonieartigem Zustand im Neugeborenenalter (German: a syndrome of obesity, short stature, cryptorchism and oligophrenia after decreased muscle tone in an infant). Schweiz Med Wschr 1956;86:1260-1.

External links

• OMIM176270
• AAFP OverviewA clear and concise overview of PWS.
• Prader-Willi Syndrome Associations:

UK

USA

NZ

South Africa

International Prader-Willi Syndrome Organization

• PWS Notes A wiki designed to provide useful background on Prader-Willi Syndrome (PWS) for parents and to organize medical information that may be helpful for future research directions

Parts of this page were taken directly from genetests.org, copyright University of Washington1993-2006de:Prader-Willi-Syndrom es:Síndrome de Prader-Willi fr:Syndrome de Prader-Willi he:?????? ???? ???? nn:Prader-Willi syndrom zh:????????

This article is licensed under the GNU Free Documentation License.
It uses material from the http://en.wikipedia.org/wiki/Prader-Willi+syndrome Wikipedia article Prader-Willi syndrome.