P rader-Willi syndrome (PWS) is a genetic disorder with an estimated prevalence of between approximately 1 in 10,000 and 1 in 25,000 live births. [1][2][3][4] PWS is characterized by hypotonia and developmental delay, short stature, small extremities and characteristic facies, hyperphagia leading to obesity, and other behavioral problems. 5,6 Symptoms of obstructive sleep apnea (OSA) may be difficult to elicit in patients with PWS, although caregivers often describe snoring, nocturnal breathing difficulties, and restless sleep in patients with PWS. 7 Excessive daytime sleepiness, arising from a variety of causes, is a cardinal feature of both OSA syndrome and PWS. 8,9 Patients with PWS may be at increased risk of OSA 10-12 due to obesity, facial dysmorphism, 11 and sticky secretions. 12 However, the associated hypothalamic disorders, including hypogonadism, hyperphagia, and hypotonia, 5 suggest that central neurologic developmental abnormalities may also directly affect sleep and breathing through unknown neurologic mechanisms. Although there have been advances in understanding of this disorder, particularly of the genetic abnormalities, including the linkage to chromosome 15q11-13, 14-19 a specific Prader-Willi gene has not yet been identified. There have been several genes and transcripts mapped within the PWS critical region and 2 identified protein products, and several of these are subject to genomic imprinting. These "controlling genes" are known to effect the expression of PWS. Clinical features are specific and some improve (e.g., hypotonia) with age (after about the first 12 months of age). 20 Some features may not be as severe to the same extent in all affected people. Understanding the genetic bases and putative central mechanisms that lead to the PWS phenotype may lead to molecular targets for OSA, hyperphagia, and obesity in PWS.
