Tuberous sclerosis complex (TSC)

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.

Tuberous sclerosis complex (TSC) is a genetic disorder that can affect neurodevelopment, mental health, and multiple organ systems. It occurs as an autosomal dominant genetic condition, with most affected individuals having a de novo pathogenic variant and a substantial minority inheriting the condition from an affected parent; therefore, absence of a relevant family history does not exclude the diagnosis. A distinctive presentation may include the combination of seizures and characteristic cutaneous angiofibromas or other skin lesions.

It can present with psychiatric features such as autism-spectrum features, attention-deficit symptoms, anxiety, depression, obsessive-compulsive symptoms, behavioural dysregulation, impulsivity, aggression, self-injurious behaviours, and psychosis, as part of the broader Tuberous Sclerosis Complex–Associated Neuropsychiatric Disorders (TAND) phenotype. TAND manifestations may become apparent or clinically significant at any age, including during adolescence or adulthood.

Other characteristic features include seizures, often beginning in infancy or early childhood; developmental delay and intellectual disability of variable severity. Cortical tubers, subependymal nodules, and subependymal giant cell astrocytomas are characteristic brain lesions. Cardiac rhabdomyomas may occur in infancy, while retinal hamartomas are characteristic ocular findings.

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

  • Cardiovascular: cardiac rhabdomyomas, particularly in infancy, and cardiac arrhythmias may occur.

  • Respiratory: lymphangioleiomyomatosis and other cystic lung disease may occur, predominantly in adult females.

  • Renal/electrolytes: renal angiomyolipomas and renal cystic disease are common; renal impairment, hypertension, and, rarely, renal cell carcinoma may occur.

  • Musculoskeletal: bone cysts, sclerotic bone lesions, and other skeletal abnormalities may occur.

  • Dermatologic: hypomelanotic macules, facial angiofibromas, shagreen patches, ungual fibromas, and other characteristic skin lesions are common.

Early diagnosis is important to identify and treat seizures early, recognize potentially serious renal, cardiac, pulmonary, and neurologic complications, identify TSC-associated neuropsychiatric manifestations and provide appropriate developmental and psychiatric support, guide genotype- and manifestation-specific surveillance and treatment, and improve prognosis and quality of life.

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.