Genetics of Childhood Disorders: XV. Prader-Willi Syndrome: Genes, Brain, and Behavior

Abstract

Prader-Wdli syndrome (PWS) is a developmental disorder characterized by mental retardation or learning disability, infantile hypotonia and poor suck reflex, growth retardation, delayed sexual development, and the childhood onset of pronounced hyperphagia Food-related difficulties are the most striking and widely recognized sequelae of this syndrome. Without appropriate dietary and behavioral intervention, almost everyone with PWS will become dangerously obese. However, in addition to these well-known problems with food, those with PWS also suffer from a range of psychiatric and behavioral difficulties, including high rates of depression, obsessions, and compulsions. PWS is a relatively rare disorder, with an incidence of approximately 1 in 10,OOO to 15,000 live births. Nonetheless, it has figured prominently in the recent history of genetics. This is due in large part to its surprising relationship with Angelman syndrome (AS) and the resulting identification of genomic imprinting in humans. Moreover, as research into the various aspects of this disorder has progressed, it has become increasingly evident that PWS may provide neuroscientists a valuable window into the complex interplay of genes, brain, and behavior. At first glance, the genetics of PWS appear to be rather straightforward. For most affected individuals, a sporadic (as