Prader-Willi syndrome (PWS), a condition initially described by Prader, Labhard, and Willi in 1956, is a neurodevelopmental disorder with a clinical presentation that includes neonatal hypotonia, obesity, mental retardation, and behavioral abnormalities. After introduction of high-resolution chromosome analysis, PWS was the first abnormal phenotype found to be associated with a submicroscopic chromosomal deletion. The PWS-asso-ciated microdeletion spans about 4 Mbp in the chromosomal region 15q11q13 and always affects the paternally derived chromosome. In this chromosomal region several genes are imprinted—only their paternally derived alleles are functional. Among them, candidates for major gene contributors for the PWS phenotype are the unusual polycistronic gene SNURF-SNRPN, the gene NDN, and others. Four main molecular mechanisms may lead to deficiencies of genes located in the PWS area. In all PWS cases, with the exception of the rare cases of chromosomal balanced translocations, DNA methylation abnormalities can be detected and are used for diagnostic evaluations. Although in most cases the recurrence risk in the family is lower than 1%, complete diagnostic evaluation and determination of the particular PWS type is always appropriate because in some rare instances the recurrence risk is increased. The management of PWS is generally supportive. One useful recent development in PWS therapy is the use of growth hormone (GH) to counteract obesity and short stature.
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