Prader-Willi Syndrome

Uniparental Disomy 15 (UPD15mat)

Klinische Symptomatik

Infants with Prader-Willi syndrome usually exhibit pronounced muscular hypotonia and feeding difficulties. During childhood excessive overweight develops due to uncontrollable hyperphagia. Additional signs are small stature, hypogonadism, characteristic facial features (bifrontal diameter, almond-shaped eyes) as well as learning disability and in some cases diabetes mellitus.

Genetik

The Prader-Willi syndrome may be caused by several genetic mechanisms:

1. Deletion of the paternally derived Prader-Willi syndrome/Angelman syndrome (PWS/AS) region on chromosome 15q11.2-q13
   The most common cause for PWS in 70% of cases. A deletion on the paternal chromosome can arise de novo or can result from a balanced translocation in the father.
2. Maternal uniparental disomy 15
   About 30% of children with PWS exhibit two chromosomes 15 both deriving from the mother. A paternally contributed chromosome 15 is missing.
3. Imprinting defect
   An imprinting defect is present in about 1% of PWS cases. This means that the corresponding genes on the paternal chromosome are switched of. The genetic mechanisms listed above all result in a methylation abnormality. They can be detected by a methylation-sensitive PCR (DNA methylation testing). To characterize the underlying genetic mechanism, further genetic studies which may include parental blood samples (linkage analysis) are necessary.
4. Unknown origin
   In only 1% the genetic origin of PWS can not be elucidated.
   The recurrence risk of a PWS, especially for siblings of an affected child, depends on the underlying genetic mechanism.

Häufigkeit

Approx. 1 : 10 000

 

Diagnostik