Tuberous sclerosis: A genetic disorder characterized by abnormalities of the skin, brain, kidney, and heart. The skin abnormalities are present in all cases and may include tiny benign tumors (angiofibroma) on the face and depigmented areas anywhere on the body. The brain abnormalities are mainly benign cortical tumors (tubers) which cause seizures, developmental delay, and mental retardation. The kidneys often contain multiple cysts and benign tumors (angiomyolipomas). The heart problems include arrhythmias and benign heart muscle tumors (rhabdomyomas).
The diagnosis of tuberous sclerosis is usually made by the medical history and clinical observation. For example, a child with a known seizure disorder is seen to have white spots on the skin visible under ultraviolet light.
Tuberous sclerosis is inherited in an autosomal dominant manner and results from mutation of either one of two genes: the TSC1 gene on chromosome 9 or the TSC2 gene on chromosome 16. The TSC1 gene makes a protein called tuberin. These two proteins function together in cells to regulate and prevent the overgrowth of cells into tumors. When either the TSC1 or TSC2 gene is mutated, nonfunctional versions of hamartin or tuberin are made in the cell. As a result, the hamartin-tuberin protein complex does not form and cells divide too frequently, leading to the formation of noncancerous tumors. Two-thirds of cases of tuberous sclerosis are due to new mutations and the other third are inherited from a parent.