Endocrine disorders in Prader-Willi syndrome: a model to understand and treat hypothalamic dysfunction

Lancet Diabetes Endocrinol. 2021 Apr;9(4):235-246. doi: 10.1016/S2213-8587(21)00002-4. Epub 2021 Feb 26.


Prader-Willi syndrome is a rare genetic neurodevelopmental disorder resulting from the loss of expression of maternally imprinted genes located in the paternal chromosomal region, 15q11-13. Impaired hypothalamic development and function is the cause of most of the phenotypes comprising the developmental trajectory of Prader-Willi syndrome: from anorexia at birth to excessive weight gain preceding hyperphagia, and early severe obesity with hormonal deficiencies, behavioural problems, and dysautonomia. Growth hormone deficiency, hypogonadism, hypothyroidism, premature adrenarche, corticotropin deficiency, precocious puberty, and glucose metabolism disorders are the main endocrine dysfunctions observed. Additionally, as a result of hypothalamic dysfunction, oxytocin and ghrelin systems are impaired in most patients. Standard pituitary and gonadal hormone replacement therapies are required. In this Review, we discuss Prader-Willi syndrome as a model of hypothalamic dysfunction, and provide a comprehensive description of the accumulated knowledge on genetics, pathophysiology, and treatment approaches of this rare disorder.

Publication types

  • Review

MeSH terms

  • Animals
  • Endocrine System Diseases / genetics
  • Endocrine System Diseases / physiopathology*
  • Endocrine System Diseases / therapy
  • Humans
  • Hypothalamus / physiopathology*
  • Prader-Willi Syndrome / genetics
  • Prader-Willi Syndrome / physiopathology*
  • Prader-Willi Syndrome / therapy
  • Proteins / genetics


  • MAGEL2 protein, human
  • Proteins