Management of Hyperphagia and Obesity in Prader-Willi Syndrome

Prader-Willi syndrome (PWS) is a neurodevelopmental disorder caused by the absence of paternally expressed imprinted genes on chromosome 15q11-13. Individuals with PWS characteristically have 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. 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, if they do not exercise aggressive external control over their eating behaviors. Moreover, the main causes of death for PWS are obesity-related comorbidities such renal failure, pulmonary embolism, and respiratory and heart failure. Clinical experience with different supplements, diets, and other methods has not been encouraging. Therapeutic options for patients with PWS may be supported by recent clinical trials for a number of medicines. This report reviews the causes and management of hyperphagia, as well as previous and recent clinical trials for treating hyperplasia in PWS. We hope that novel treatments currently in development will help alleviate the complex metabolic issues associated with PWS.