Development of the eating behaviour in Prader-Willi Syndrome: advances in our understanding

Abstract

Prader-Willi Syndrome (PWS) is a genetically determined neurodevelopmental disorder associated with mild to moderate intellectual disability, growth and sex-hormone deficiencies and a propensity to overeat that leads to severe obesity. The PWS phenotype changes from an early disinterest in food to an increasing pre-occupation with eating and a failure of the normal satiety response to food intake. The prevention of severe obesity is primarily through strict control of access to food and it is this aspect that most limits the independence of those with PWS. This review considers the eating disorder in PWS, specifically how the as yet uncertain genetics of the syndrome and the transition from the early to the later phenotype might account for the later hyperphagia. On the basis of behavioural and imaging studies, a failure of satiety and excessive activation of neural reward pathways have both been suggested. We speculate that the overeating behaviour, consequent upon one or other of the above, could either be due to a direct effect of the PWS genotype on the feeding pathways of the hypothalamus or a consequence of prenatal changes in the regulation of genes responsible for energy balance that sets a high satiation threshold. Understanding the overeating in PWS will lead to more focused and successful management and ultimately, treatment of this life-threatening behaviour.