Tuberous Sclerosis

Tuberous sclerosis, also called tuberous sclerosis complex (TSC), is a disease marked by the formation of widespread benign tumors throughout the body. This disease has a well-established molecular link, which stems from defects or mutations in either of two genes TSC1 and TSC2. Widespread consequences of these mutations lead to a triad of multiple organ system disorders. Eighty percent of patients present with benign tumors in the brain that cause disabling neurological abnormalities including epilepsy, mental retardation, and autism. TSC is also associated with multiple benign tumors of other vital organs, which include the heart, kidneys, skin, lungs, and eyes.

Individuals with TSC may experience none or all of the symptoms with varying degrees of severity. The name tuberous sclerosis comes from the characteristic tuber or root-like growths in the brain. TSC affects as many as 25,000 to 40,000 individuals in the United States and about 1 to 2 million individuals worldwide, with an estimated prevalence of one in 5,000 to 10,000 newborns. TSC occurs in all races, ethnic groups, and in both genders. There is no cure for TSC, although treatment is available for a number of the symptoms.

TSC is an autosomal-dominant disorder, with full penetrance, which means that the disease is carried by a dominant gene, and if a parent has a mutation in the TSC1 or TSC2 gene, each offspring has a 50 percent chance of developing the disorder.

The TSC1 gene, on chromosome 9, and the TSC2 gene, on chromosome 16, produces two proteins, hamartin and tuberin, in a normal individual. These proteins help orchestrate a signaling cascade within the cell that controls growth and proliferation. Defects or mutations in TSC1 or TSC2 causes disruption of the signaling cascade, causing the affected cell to grow uncontrolled. Scientists are currently studying this signaling cascade and are developing drugs to prevent the growth of established tumors. Rapamycin, also known as sirolimus, has been shown in preliminary clinical studies to induce tumor regression in patients with TSC.

The major clinical features of TSC are the cortical tubers and neurologic abnormalities. Cognitive deficits, including learning disabilities, and seizures begin in infants before 2 years of age in over 70 percent of cases. Antiepileptic drugs may be used to control seizures, and medications may be prescribed for behavior problems. Intervention programs including special schooling and occupational therapy may benefit individuals with special needs and developmental issues.

Individuals with TSC may gain further information from a TSC clinic that specializes in diagnosis, primary care, and treatment of the disorder. Physicians and patients are referred to the Tuberous Sclerosis Alliance Web site (http://www.tsalliance.org) to gain any further useful information, which includes current research, therapeutic developments, clinical trials, counseling, and general support, and TSC clinic locations.