Tuberous sclerosis

Tuberous sclerosis is a genetic disorder characterized by the growth of numerous noncancerous tumors in many parts of the body. These tumors can occur in the skin, brain, kidneys, and other organs, in some cases leading to significant medical problems.

The signs and symptoms of tuberous sclerosis vary according to the location of tumor growth. Virtually all affected people have skin abnormalities, including patches of unusually light-colored skin, areas of raised and thickened skin, and growths under the nails. Tumors on the face (facial angiofibromas) are also common, beginning in childhood. Many people with tuberous sclerosis have noncancerous brain tumors. Neurologic symptoms can include seizures, behavioral problems such as hyperactivity and aggression, and intellectual disability or learning problems. Some affected children have the characteristic features of autism, a developmental disorder that affects communication and social interaction. Kidney tumors are also common in people with tuberous sclerosis; these growths can cause serious problems with kidney function and may be life-threatening in some cases. Additionally, tumors can develop in the heart, lungs, and the light-sensitive tissue at the back of the eye (the retina).

Tuberous sclerosis affects about 1 in 6,000 people.

Mutations in the TSC1 and TSC2 genes cause tuberous sclerosis. The TSC1 and TSC2 genes provide instructions for making the proteins hamartin and tuberin, respectively. Within cells, these two proteins likely function together as a protein complex that helps regulate cell growth and size. The proteins act as tumor suppressors, which normally prevent cells from growing and dividing too fast or in an uncontrolled way. Mutations in either the TSC1 or TSC2 gene lead to the production of a nonfunctional version of hamartin or tuberin. As a result, cells can divide excessively to form the numerous tumors associated with tuberous sclerosis.

Read more about the TSC1 and TSC2 genes.

Tuberous sclerosis is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. About two thirds of cases result from new mutations in the TSC1 or TSC2 gene. These cases occur in people with no history of tuberous sclerosis in their family. In the remaining cases, an affected person inherits an altered TSC1 or TSC2 gene from a parent who has the disorder. TSC1 mutations appear to be more common in familial cases of tuberous sclerosis, while mutations in the TSC2 gene tend to occur more frequently in affected individuals with no family history of the disorder.