Current status and perspectives in the treatment of Prader-Willi syndrome

Abstract

Introduction: Prader-Willi syndrome (PWS) is a neurometabolic genetic disorder with chromosomal 15q11-q13 deletions or uniparental disomy with absence of paternally expressed genes affecting 1/12,000 – 1/15,000 newborns. The syndrome is characterized by hypotonia, intellectual disability, behavioral problems, psychiatric phenotypes, short stature, central hypocorticism, pubertal insufficiency and hypogonadism leading to osteoporosis. The most life-threatening characteristic is excessive appetite, which leads to morbid obesity and diabetes and its related complications.Areas covered: In this paper, the authors review evidence-based papers that present the management of patients with PWS, involving aspects of reduced GH secretion, hypogonadotropic hypogonadism, abnormal appetite control and high pain threshold, all suggesting hypothalamic-pituitary dysfunction. The treatment of these homeostatic alterations is presented, and the consideration of a multidisciplinary approach and future perspectives are discussed. Finally, the authors briefly review the current status of treatment and perspectives specific for PWS.Expert opinion: Despite the detailed knowledge about obesity mechanisms regulated at the hypothalamic level, the pharmacological intervention is limited currently to substitution of proven endocrine deficiencies (growth hormone, thyroxine, sex steroids, glucocorticoids), prevention and treatment of metabolic complications (the most severe being diabetes) and osteoporosis. Treatment of mental disturbances and skin-picking, severe obesity and altered body composition often requires a team including a pediatrician, an endocrinologist, a psychiatrist, a bariatric surgeon and strong support from the family and caregivers.