, Ji Eun Moon, Yeo Jin Jung, Young Ae Yu Prader-Willi syndrome (PWS), which is considered the most common genetic form of obesity, results from the absence of imprinted genes in the paternally derived PWS critical region located on chromosome 15q11.2−13. Infants with PWS exhibit poor sucking, neonatal hypotonia, and delayed motor milestones. These patients begin to experience hyperphagia and obesity from 2 to 3 years of age. PWS is a multisystemic disorder, and its clinical manifestations include developmental delay/intellectual disability, behavioral problems, dysmorphic facial features, short stature, scoliosis, and endocrine abnormalities such as hypogonadism, growth hormone deficiency, hypothyroidism, and central adrenal insufficiency. Although the underlying mechanism of hyperphagia is not completely understood, hypothalamic and endocrine dysregulation is believed to be responsible for the lack of satiety and abnormal food-seeking behaviors that lead to severe obesity. The management of PWS requires a multidisciplinary team approach. Early diagnosis and comprehensive early intervention are essential to prevent the development of obesity-related morbidities, including metabolic syndrome, diabetes mellitus, obstructive sleep apnea, respiratory failure, pulmonary hypertension, and cardiovascular complications. Although several clinical trials have been conducted on the pharmacologic treatment of obesity in PWS, no drugs have demonstrated a consistently beneficial effect to date. Nevertheless, ongoing research efforts should be directed toward understanding the mechanism of the unique obesity phenotype of PWS and developing pharmacological therapies.
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, Sung Yoon Cho Prader-Willi syndrome (PWS) is a neurodevelopmental disorder caused by the absence of paternally expressed imprinted genes on chromosome 15q11–13. Individuals with PWS typically experience feeding difficulties and a lack of appetite in infancy, followed by weight gain, uncontrolled appetite, and a lack of satiety. Hyperphagia in PWS is exacerbated by impaired satiety, low energy expenditure, and intellectual difficulties, including obsessive-compulsive disorder and/or autistic behaviors. Without rigorous external management of their eating behaviors, patients with PWS become severely obese and are at a higher risk of obesity-related morbidities, such as type 2 diabetes, obstructive sleep apnea, and hypertension. Moreover, the main causes of death for PWS are obesity-related comorbidities, such as renal failure, pulmonary embolism, and respiratory and heart failure. Clinical experiences with different supplements, diets, and other methods have not been encouraging. However, therapeutic options for patients with PWS may be improving, based on recent clinical trials for a number of medications. This report reviews the causes and management of hyperphagia, as well as previous and recent clinical trials aimed at treating hyperplasia in PWS. We are optimistic that the novel treatments currently in development will help alleviate the complex metabolic issues associated with PWS.
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