Prader-Willi Syndrome

Abstract

Abstract Prader-Willi syndrome (PWS) is a complex multisystem syndrome that occurs with a frequency of approximately 1/10,000 to 1/20,000 and has significant morbidity, including central hypotonia, mild mental retardation/developmental disabilities, a characteristic behavior disorder, growth deficiency, obesity compounded by a centrally driven excessive appetite (hyperphagia), growth hormone deficiency, and hypogonadism. It is the most commonly known genetic cause of obesity. Prader-Willi syndrome is one of the best examples of a pattern of inheritance called genomic imprinting. In contrast to Mendelian inheritance, the imprinted genes have differential expression, depending on the parental origin. In the 15q11–q13 chromosomal region, there are genes that are expressed only if they are paternally derived and others that are expressed only if maternally derived. Prader-Willi syndrome results from the loss of expression of paternally derived genes by a variety of mechanisms, which include large deletions (70%–75%), maternal uniparental disomy (UPD, 20%–30%), and imprinting defects (2%–5%).2,3 DNA methylation analysis will correctly diagnose more than 99% of cases and is the most sensitive genetic test available. It is also more sensitive than the clinical diagnostic criteria that were originally published in 1993 by Holm et al. Therefore, all patients suspected of having PWS should have definitive genetic testing since there is significant variability in the clinical phenotype (Table 16–1).