Prader-Willi syndrome is a genetic disorder in which seven genes (or some subset thereof) on chromosome 15 are missing or unexpressed (chromosome 15q partial deletion). It was identified in 1956 by Andrea Prader, Heinrich Willi, Alexis Labhart, and Guido Fanconi of Switzerland. more...
Prader-Willi syndrome (PWS) is characterized by:
- Severe hypotonia and feeding difficulties in early infancy.
- Excessive eating and gradual development of morbid obesity in later infancy or early childhood, unless externally controlled.
- Mental retardation and distinctive behavioral problems in all patients.
- Hypogonadism is present in both males and females.
- Short stature is common.
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 chromosome 15q11.2-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.
PWS is caused by absence of the paternally derived PWS/AS region of chromosome 15 by one of several genetic mechanisms, including uniparental disomy, imprinting mutations, chromosome translocations, and gene deletions. The genes responsible 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 imprinting in 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 testing is possible for any of the known genetic mechanisms.
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