Tuberous sclerosis complex (TSC) is an autosomal dominant condition characterized by tumors in the brain, eye, and kidney. Dermatologic manifestations include both ash leaf and shagreen patches. Neurologic conditions are quite common and include epilepsy and mental retardation. Germline mutations can be found in two tumor suppressor genes, TSC1 (hamartin) and TSC2 (tuberin). Renal manifestations are highly penetrant and include angiomyolipomas, cysts, and clear cell RCC (Fig.). Chronic kidney disease is also common in these patients, but the etiology is unknown. Clear cell RCC is not common, but when it occurs, it can behave aggressively. Angiomyolipomas can become quite large and cause local symptoms. The risk of hemorrhage increases with size and can be lifethreatening. Loss of TSC2 in animal models has demonstrated upregulation of HIF and mTORC1, similar to VHL-related clear cell RCC.
Fig. 1 Bilateral, multifocal angiomyolipoma in a patient with TSC