Tuberous Sclerosis

Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder caused by mutations in TSC1 or TSC2 genes, which encode proteins forming the TSC complex that negatively regulates mTOR signaling. Loss of TSC1/TSC2 function leads to uncontrolled mTOR activation, resulting in widespread development of benign tumors (hamartomas) in multiple organs. Brain involvement occurs in 80-90%, manifesting as cortical tubers (benign focal malformations), subependymal nodules, and subependymal giant cell astrocytomas (SEGAs), which frequently cause seizures and increased intracranial pressure. Kidney involvement occurs in 50%, ranging from benign cysts to angiomyolipomas and renal cell carcinomas. Skin manifestations are nearly universal and include facial angiofibromas, ash-leaf spots (hypopigmented macules), shagreen patches, and ungual fibromas. Cardiac rhabdomyomas occur in infants and usually regress over time. Pulmonary LAM (lymphangioleiomyomatosis) affects approximately 30% of women, causing progressive lung disease and respiratory complications.