Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two distinct disorders caused by imprinting defects in the chromosome 15q11.2-q13 region. Unaffected individuals have one methylated allele (maternal) and one unmethylated allele (paternal).

Prader-Willi syndrome (PWS) is caused by absence of the paternal (unmethylated) allele at chromosome locus 15q11.2-q13, which causes a constellation of physical and cognitive findings. The absence of the paternal allele can be caused by a number of genetic mechanisms.

Prader-Willi syndrome occurs with a frequency of 1 in 10,000 to 1 in 30,00 births and is characterized by specific facial features (almond shaped palpebral fissures, narrowed bi-frontal diameter), significant hypotonia during infancy, and hypogonadism. Hypotonia in affected children typically improves by 2 to 3 years of age, however by early childhood most affected individuals exhibit central obesity due to hyperphagia and global developmental delay.

Angelman syndrome (AS) is a genetic neurologic disorder caused by the absence of the maternal (methylated) allele at chromosome locus 15q11.2-q13. The absence of the maternal allele can be caused by a number of genetic mechanisms as well.

Angelman syndrome occurs with a frequency of 1 in 20,000 births and is characterized by happy demeanor, characteristic facial features, seizures, ataxia, episodes of paroxysmal laughter, and lack of speech development. Individuals with Angelman syndrome exhibit cognitive and developmental delay without evidence of regression, minimal language skills, ataxia, tremors and seizures.

Methylation study of the 15q11.2-q13 region is considered a first-tier diagnostic test in the work-up of either of these imprinting conditions. If methylation studies are positive, further evaluation, such as FISH analysis to evaluate for chromosome 15 imprinting center deletion, may be performed to determine the underlying genetic mechanism, which has implications with respect to recurrence risk. FISH analysis for the PWS/AS critical region is available in our laboratory upon request.