XXYY 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.

XXYY syndrome is a genetic disorder that can affect neurodevelopment, mental health, and multiple organ systems. It typically occurs as a sporadic chromosomal abnormality rather than as an inherited disorder, so a relevant family history would be unexpected. It occurs in males.

It can present with psychiatric features such as anxiety, depression, attention-deficit symptoms, autism-spectrum features, social difficulties, behavioural dysregulation, impulsivity, and, rarely, psychosis. Psychiatric manifestations may become apparent during adolescence or adulthood, and psychotic disorders have been reported in adults with XXYY syndrome.

Other characteristic features include developmental delay, intellectual disability of variable severity, speech and language difficulties, learning difficulties, motor-coordination difficulties, hypotonia, intention tremor, tics, and seizures in some individuals. Characteristic facial features may include hypertelorism, epicanthal folds, narrow or upslanting palpebral fissures, full lips, a prominent brow, and a relatively long face. Tall stature and hypogonadism with small testes and infertility are also characteristic.

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

  • Cardiovascular: congenital heart disease and other cardiovascular abnormalities may occur; deep vein thrombosis and peripheral vascular disease have also been reported.

  • Respiratory: asthma and recurrent respiratory problems may occur.

  • Renal/electrolytes: renal and urinary tract abnormalities may occur.

  • Endocrine: hypergonadotropic hypogonadism with low testosterone, small testes, infertility, reduced facial and body hair, and gynecomastia; type 2 diabetes may also occur.

  • Musculoskeletal: joint laxity, pes planus, radioulnar synostosis, scoliosis, and other skeletal abnormalities may occur.

  • Dermatologic: acne and sparse body hair may occur.

Early diagnosis is important to identify potentially treatable medical contributors to psychiatric, developmental, and cognitive presentations, recognize hypogonadism and other multisystemic complications, guide appropriate endocrine and medical surveillance, and enable timely treatment of psychiatric illness and other comorbidities.

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.