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. International Journal of Obesity (2011) IntroductionWe review the present state of knowledge on the eating disorder and potential resultant life-threatening obesity that is associated with Prader-Willi Syndrome (PWS), a genetically determined neurodevelopmental disorder affecting 1 in 22-25 000 live births.1-3 The aims of the review are: first, to consider our understanding of the eating disorder associated with PWS primarily from a behavioural and neuroscience perspective; second, to speculate as to the possible mechanisms that might directly or indirectly link the PWS genotype to the 'eating' phenotype; and third, to reflect on the implications for future research and for treatment. We discuss the major theories that could account for eating behaviour and whether any of these adequately explain the complex array of characteristics that exist in PWS and fit with what we know about the pathophysiology and the genetics of the disorder. The main discussion items include considering PWS as a disorder of satiety, as well as theories of hyper-responsive rewards systems and over-sensitivity to food stimuli, as has been proposed in general obesity. Further, we consider the importance of the prenatal environment and examine the possibility that people with PWS have an altered inner physical awareness, as shown by abnormal pain responses, and how this may alter the eating behaviour. MethodThis review has been carried out through a search of relevant articles primarily on the PubMed search engine (www. pubmed.gov) using 'eating behaviour Prader-Willi syndrome OR Prader Willi syndrome' as the search term. As the eating behaviour is such a key feature of t...

Anomalous basal ganglia connectivity and obsessive–compulsive behaviour in patients with Prader Willi syndrome

“…Altered eating behaviour in patients with Prader Willi syndrome is considered to be a failure of satiety 51,52 potentially related to hypothalamic dysfunction. 53 Our results may provide direct evidence of the abnormal association between very basic limbic structures governing internal homeostasis (i.e., hypothalamus and amygdala) and the ventral frontostriatal system related to motivation, reward and satiety.…”

Can we modulate physical activity in children?

“…6 Thus, brain damage, 7 leptin deficiency 8 and other genetic conditions such as Prader-Willi syndrome 9 are all well-recognised disorders affecting appetite control, which result in obesity. Rowland 10 first used the term 'activitystat' to conceptualise a corresponding centre for the control of physical activity, and we and others have embraced the concept.…”

Treino parental para manejo comportamental de crianças com Síndrome de Prader-Willi: impacto sobre a saúde mental e práticas educativas do cuidador

“…In other cases occurrences of the imprinting phenomenon or other rearrangements of chromosome 15 are reported. The disease incidence is 1: 10,000 to 30,000 births 1.2. The cognitive and behavioral phenotype observed in people with PWS is characterized by frequent episodes of hyperphagia, stealing food, tantrums, lying behavior, mood swings, anxiety, sadness, aggression and auto aggression, stubbornness and repetitive speech, hypersomnia, compulsive behaviors, deficits in cognitive abilities such as attention and executive functions (especially inhibitory control, working memory and self-regulation) and deficits in visuospatial skills [3][4][5][6][7] . Of these described characteristic phenotypes, the problems most difficult to manage are hyperphagia; stubborn behavioral patterns; challenging, aggressive, oppositional and manipulative behaviours; food theft and lying, which become more frequent and severe with increasing age [8][9][10][11] .…”