Obesity in Prader–Willi syndrome: physiopathological mechanisms, nutritional and pharmacological approaches

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.

Craniopharyngioma, Chronotypes and Metabolic Risk Profile

“…Lifestyle modification, which involves altering and maintaining long-term habits that include being physically active and healthy eating, remains the treatment of choice [39], although with poor and short-term results in any case [40]. This is especially true in patients with CP and other hypothalamic obesity syndromes, as they are poor responders to dietary and lifestyle modifications [8,[41][42][43] and often show marked weight gain even after forced caloric restriction, suggesting that hyperphagia is not the central problem. Chronotype and circadian rhythms are emerging risk factors of obesity and cardiometabolic diseases [21,22].…”

“…The scores ranged from 16 to 86. Individuals, based on their scores, were categorised as being a morning (59-86), neither or intermediate (42)(43)(44)(45)(46)(47)(48)(49)(50)(51)(52)(53)(54)(55)(56)(57)(58), or evening (16-41) chronotype.…”

Anti-Obesity Medication Use in Children and Adolescents with Prader–Willi Syndrome: Case Review and Literature Search

“…It is imperative that we find improved treatments for the obesity associated with PWS. Obesity is a leading cause of mortality and high morbidity rates among individuals with PWS, with a 3% annual death rate across all ages [ 47 , 48 , 49 ]. This contemporary review and case series details 10 cases of youth with PWS on AOMs for weight management and describes how AOMs can be effective at decreasing appetite and reducing BMI for certain patients with PWS.…”

Case Report: Hepatic Adenomatosis in a Patient With Prader–Willi Syndrome

“…In the neonatal period, there is severe hypotonia with poor suck and feeding difficulties followed in infancy or early childhood by excessive eating and gradual development of morbid obesity. The syndrome is considered the most common genetic cause of obesity, occurring in 1:10,000–1:30,000 live births ( 1 ). Obesity and its related complications are the most common causes of morbidity and mortality in PWS.…”