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Prader-Willi Syndrome

Uniparental Disomy 15 (UPD15mat)

Clinical Features

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.

Genetic Information

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.

Prevalence

Approx. 1 : 10 000

 

Diagnostic

 

Indication

Clinically suspected PWS,

infants with pronounced muscular hypotonia,

infants with hyperphagia, obesity and small stature in association with corresponding dysmorphic features and hypogonadism.

Method

Methylation-sensitive PCR,

in case of abnormal methylation pattern the genetic defect is elucidated via chromsomal analyses also involving the parental blood samples.

Sample Requirement

2 to 4 ml of EDTA blood

2 to 5 ml of heparinized blood for chromosomal analysis

Prenatal diagnostics upon request

Duration

2 weeks

OMIM

176270 PWS



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