Abstract
Prader–Willi syndrome (PWS) is a genetic disorder caused by the lack of expression of genes on the paternally inherited chromosome 15q11.2-q13 region. The three main genetic subtypes are represented by paternal 15q11-q13 deletion, maternal uniparental disomy 15, and imprinting defect. Clinical picture of PWS changes across life stages. The main clinical characteristics are represented by short stature, developmental delay, cognitive disability and behavioral diseases. Hypotonia and poor suck resulting in failure to thrive are typical of infancy. As the subjects with PWS age, clinical manifestations such as hyperphagia, temperature instability, high pain threshold, hypersomnia and multiple endocrine abnormalities including growth hormone and thyroid-stimulating hormone deficiencies, hypogonadism and central adrenal insufficiency due to hypothalamic dysfunction occur. Obesity and its complications are the most common causes of morbidity and mortality in PWS. Several mechanisms for the aetiology of obesity in PWS have been hypothesized, which include aberration in hypothalamic pathways of satiety control resulting in hyperphagia, disruption in hormones regulating appetite and satiety and reduced energy expenditure. However, despite the advancement in the research field of the genetic basis of obesity in PWS, there are contradictory data on the management. Although it is mandatory to adopt obesity strategy prevention from infancy, there is promising evidence regarding the management of obesity in adulthood with current obesity drugs along with lifestyle interventions, although the data are limited. Therefore, the current manuscript provides a review of the current evidence on obesity and PWS, covering physiopathological aspects, obesity-related complications and conservative management.
Highlights
Prader–Willi syndrome (PWS) is a complex multisystem disorder that is caused by the lack of expression of paternally active genes in the PWS critical region on chromosome 15 (15q11.2-q13)
In a pilot study of 21 children and adolescents with PWS with insulin resistance and glucose intolerance on oral glucose tolerance test (OGTT) that started for this reason treatment with metformin, it has been observed an improvement of food-related distress and anxiety, evaluated by Hyperphagia Questionnaire (HQ) without a reduction in body weight [77]
Obesity represents one of the main complications of PWS. It predisposes to the risk of developing type 2 diabetes mellitus (T2DM), dyslipidemia and cardiovascular events, mostly at a young age
Summary
Prader–Willi syndrome (PWS) is a complex multisystem disorder that is caused by the lack of expression of paternally active genes in the PWS critical region on chromosome 15 (15q11.2-q13). A subsequent study found that circulating ghrelin levels were elevated in children and adult subjects with PWS compared to both lean and obese controls as a result of increased active AG, whereas UAG was relatively low.
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