Chapter

Prader-Willi Syndrome

Rachel Wevrick

in Genetics of Obesity Syndromes

Published on behalf of Oxford University Press

Published in print July 2009 | ISBN: 9780195300161
Published online October 2012 | e-ISBN: 9780199975198 | DOI: http://dx.doi.org/10.1093/med/9780195300161.003.0012

Series: Oxford Monographs on Medical Genetics

Prader-Willi Syndrome

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The year 2006 marked two important anniversaries in the history of Prader-Willi syndrome (PWS): 50 years since the description of PWS as a syndrome by Dr. Andrea Prader and colleagues was published in the Swiss Medical Weekly (Prader et al. 1956) and 25 years since the discovery of a genetic defect of chromosome 15 described by Dr. David Ledbetter and colleagues in the New England Journal of Medicine (Ledbetter et a. 1981). In the first description of PWS as a syndrome, three physicians at the Zurich Children's Hospital, Drs. Prader, Alexis Labhart, and Heinrich Willi, insightfully described similarities among a set of nine individuals seen at their clinic. These commonalities led them to the conclusion that this syndrome, later to be called “Prader-Willi syndrome,” was distinct from other clinically overlapping disorders. The constellation of symptoms they described included small stature, small hands and feet, obesity, mental retardation, infantile hypotonia, and cryptorchidism. Notably, they found no evidence for heritability of PWS, nor evidence of embryological insult as a cause of the disorder.

Additional reports soon followed that were largely descriptive in nature, but by the 1980s it was appreciated that nutritional management and appropriate psychological management could go a long way to avoiding the impact of uncontrolled obesity on health. Earlier diagnosis then improved opportunities for intervention in younger children. In the late 1960s and 1970s, reports of familial recurrences emerged that suggested a genetic component to this largely sporadic disorder. The involvement of chromosome 15in rare cases of PWS in which a cytogenetic abnormality was visible foretold the identification of a small de novo deletion on the long arm of chromosome 15in the majority of individuals with a clinical diagnosis of PWS. Soon after, the parental origin of the deletion was defined (Butler and Palmer 1983), and uniparental disomy was identified as a cause of nondeletion PWS (Nicholls et al. 1989). However, it is only within the last two decades that improved understanding of the genetic etiology and pathogenesis of PWS has provided some hope for changes in the outcomes associated with the natural history of this challenging developmental disorder.

Recent advances in genetics, endocrinology, and neurology have illuminated the causes of the findings in PWS and have given more hope that therapies targeted at underlying causes will be forthcoming. Nonetheless, challenges to the management of PWS remain: The genetic defect itself is not amenable to treatment, and PWS will not be a preventable disorder in the near future. Furthermore, PWS affects many systems and structures, and these symptoms manifest at different life stages in a variable fashion in each individual. While medical management is of paramount concern in infancy, education, social well-being, and growth are major issues facing affected individuals and their families during childhood and adolescence (Goldstone 2004). The coordination of efforts that provide comprehensive management to those affected by PWS has been successful in limiting morbidity and maximizing quality of life for families. Because of these efforts, the outcomes associated with a PWS diagnosis today are vastly different from the devastating future predicted by the physicians who delivered the news to new parents two decades ago.

Chapter.  12027 words.  Illustrated.

Subjects: Clinical Genetics ; Endocrinology and Diabetes

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