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The paradox of Prader–Willi syndrome: a genetic model of starvation
Author(s) -
Cundall David
Publication year - 2004
Publication title -
child: care, health and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.832
H-Index - 82
eISSN - 1365-2214
pISSN - 0305-1862
DOI - 10.1111/j.1365-2214.2004.t01-8-00388.x
Subject(s) - starvation , angelman syndrome , failure to thrive , psychology , argument (complex analysis) , genomic imprinting , obesity , phenotype , assertion , developmental psychology , endocrinology , biology , genetics , gene , dna methylation , gene expression , computer science , programming language
People with Prader–Willi syndrome have many other problems in addition to their insatiable appetites, and Tony Holland and his colleagues from Cambridge have done much to advance our understanding of this condition. In this article, which appears under the ‘Hypothesis’ banner in the Lancet, he makes the striking assertion that all of the many problems experienced by people with Prader–Willi syndrome can be explained by considering the syndrome as a syndrome of starvation, which manifests as obesity in a food‐rich environment. They postulate that, in this syndrome, the body incorrectly interprets the absence of satiation as starvation. It had been assumed that other aspects of the phenotype, like growth hormone deficiency, central hypogonadism, low metabolic rate, lower IQ, ritualistic behaviours were all somehow related to genes on the long arm of chromosome 15. However, the authors assert that all the various aspects of the phenotype can be attributed to their starvation hypothesis and put forward two main supporting arguments. The first is all about energy balance and they present some strong evidence that the low metabolic rate and hypogonadism is centrally mediated and what one might expect with abnormal hypothalamic responsiveness. The second is about imprinted genes in the placenta. This might explain the neonatal hypotonia, failure to thrive and arrested brain development. There is little experimental evidence to support this part of the argument yet, but like all good hypotheses, it should be a stimulus to more research.