Overview
Clinical Meaning
Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by the growth of benign tumors (hamartomas) in multiple organ systems including the brai...
Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by the growth of benign tumors (hamartomas) in multiple organ systems including the brain, skin, kidneys, heart, lungs, and eyes. It results from mutations in the TSC1 gene (encoding hamartin) or TSC2 gene (encoding tuberin), which normally form a complex that inhibits the mTOR (mechanistic target of rapamycin) pathway. When this regulation is lost, cells grow and proliferate abnormally, forming characteristic hamartomatous lesions throughout the body. In the brain, cortical tubers (disorganized areas of glioneuronal tissue) disrupt normal neural circuitry and are the primary cause of epilepsy, which occurs in approximately 85% of patients. Subependymal giant cell astrocytomas (SEGAs) can grow at the foramen of Monro and cause life-threatening obstructive hydrocephalus. Skin manifestations include hypomelanotic macules (ash-leaf spots — often the earliest visible sign), facial angiofibromas (red papules on the face appearing around age 3-5), shagreen patches (rough, raised patches on the lower back), and periungual fibromas. Renal angiomyolipomas (benign tumors containing abnormal blood vessels, smooth muscle, and fat) affect approximately 80% of patients and can hemorrhage when >4...