Prader–Willi syndrome

Page most recently updated 7 September 2026

This page focuses on the reported psychiatric associations, which may be the initial presenting manifestation, and on other clinical features that may assist the psychiatrist or primary care physician in identifying the underlying diagnosis, considered through the lenses of the diagnostic lenses framework.

Prader–Willi syndrome is a genetic disorder that can affect neurodevelopment, mental health, endocrine function, and multiple organ systems. It typically occurs as a sporadic genetic or epigenetic abnormality, although the specific molecular mechanism has implications for recurrence risk and genetic counselling; familial cases can occur. A distinctive presentation may include the combination of hypotonia, obesity, and small hands and feet.

It can present with psychiatric features such as anxiety, obsessive-compulsive symptoms, behavioural rigidity, temper outbursts, irritability, aggression, impulsivity, attention-deficit symptoms, autism-spectrum features, skin-picking behaviour, and psychosis. Psychiatric manifestations may become apparent or clinically significant during adolescence or adulthood; psychotic disorders are particularly associated with the maternal uniparental disomy subtype.

From a morphologic lens perspective, other features include (but are not limited to):

  • Round face

  • Almond-shaped palpebral fissures

Other characteristic features include neonatal hypotonia with poor feeding, followed by developmental delay, intellectual disability or learning difficulties, and childhood-onset hyperphagia with an intense preoccupation with food and risk of severe obesity if food intake is not strictly controlled. Hypothalamic dysfunction contributes to hypogonadism, growth hormone deficiency, abnormal pubertal development, altered pain perception, and sleep disturbances. Characteristic facial features may include a narrow bifrontal diameter, almond-shaped palpebral fissures, a narrow nasal bridge, and a thin upper lip with downturned corners of the mouth. Scoliosis, small hands and feet, and skin picking are also characteristic.

From a multisystemic lens perspective, clinical features in other body systems include (but are not limited to):

  • Respiratory: central and obstructive sleep apnea, sleep-disordered breathing, and excessive daytime sleepiness may occur.

  • Gastrointestinal: dysphagia, gastrointestinal dysmotility, gastroesophageal reflux, and potentially serious gastric distension or other gastrointestinal complications may occur; reduced pain sensitivity may obscure acute abdominal illness.

  • Endocrine: hypogonadism with genital hypoplasia, delayed or incomplete puberty and infertility; growth hormone deficiency with short stature; hypothyroidism, impaired glucose tolerance or type 2 diabetes, and other hypothalamic endocrine abnormalities may occur.

  • Musculoskeletal: scoliosis or kyphosis, reduced muscle mass, small hands and feet, osteoporosis or reduced bone mineral density, and other skeletal abnormalities may occur.

  • Dermatologic: skin picking, which may result in chronic wounds, scarring, pigmentary changes, and secondary infection, is common.

Early diagnosis is important to recognize the characteristic transition from infantile feeding difficulties to hyperphagia, prevent severe obesity and its complications through early food-access management, identify potentially treatable endocrine and sleep abnormalities, recognize psychiatric and behavioural manifestations including psychosis, guide appropriate developmental and educational support and lifelong multisystemic surveillance, and improve prognosis and quality of life.

Selected references and further reading — Morphologic lens

Jones KL, Jones MC, del Campo M. Smith's recognizable patterns of human malformation. 8th ed. Philadelphia: Elsevier; 2021.

Reardon W. The bedside dysmorphologist: a guide to identifying and assessing congenital malformations. 2nd ed. Oxford: Oxford University Press; 2016.

Allanson JE, Biesecker LG, Carey JC, Hennekam RCM. Elements of morphology: introduction. Am J Med Genet A. 2009;149A(1):2-5. doi:10.1002/ajmg.a.32601.

Hennekam RCM, Biesecker LG, Allanson JE, Hall JG, Opitz JM, Temple IK, Carey JC; Elements of Morphology Consortium. Elements of morphology: general terms for congenital anomalies. Am J Med Genet A. 2013;161A(11):2726-2733. doi:10.1002/ajmg.a.36249.

Selected references and further reading — Multisystemic lens

Cardinal RN, Bullmore ET. The diagnosis of psychosis. Cambridge: Cambridge University Press; 2011.

Sachdev PS, Keshavan MS, editors. Secondary schizophrenia. Cambridge: Cambridge University Press; 2010.

Levenson JL, editor. The American Psychiatric Association Publishing textbook of psychosomatic medicine and consultation-liaison psychiatry. 3rd ed. Washington (DC): American Psychiatric Association Publishing; 2019.

Stern TA, Beach SR, Smith FA, Freudenreich O, Vranceau AM, Fava M, editors. Massachusetts General Hospital handbook of general hospital psychiatry. 8th ed. Philadelphia: Elsevier; 2025.

Arciniegas DB, Yudofsky SC, Hales RE, editors. The American Psychiatric Association Publishing textbook of neuropsychiatry and clinical neurosciences. 6th ed. Washington (DC): American Psychiatric Association Publishing; 2018.

Agrawal N, Faruqui R, Bodani M, editors. Oxford textbook of neuropsychiatry. Oxford: Oxford University Press; 2020.

Boland R, Verduin M, editors. Kaplan and Sadock's comprehensive textbook of psychiatry. 11th ed. Philadelphia: Wolters Kluwer; 2024.

Loscalzo J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, editors. Harrison's principles of internal medicine. 22nd ed. New York: McGraw Hill; 2025.