Tuberous sclerosis complex (TSC) is a genetic disorder that causes benign tumors to grow in all major organ systems, including the brain, skin, heart, kidney, lung, and eye. Individuals with TSC may experience complications in any or all of these organs. Symptoms vary widely from one person to the next, with some experiencing only minor skin abnormalities and asymptomatic brain lesions, and others suffering severe epileptic seizures, cognitive disabilities, and behavioral disorders. Symptoms of TSC also typically change over time within the same individual. This variability and unpredictability is a hallmark of TSC and can make accurate diagnosis difficult. It also presents challenges to those who have been diagnosed, as well as their family members and professionals who care for them.
TSC currently affects approximately 50,000 people in the United States, and 1 to 2 million individuals worldwide. Experts estimate that the incidence of TSC is 1 in every 6,000 births, with all races and ethnic groups and both genders affected equally.
For a brief overview of the clinical features of TSC, see the Interactive Timeline.
For in-depth information about TSC's effects on particular organ systems, see How TSC Affects the Body.
TSC results from a permanent change, or mutation, in one of two genes. Such a mutation can be passed from parent to offspring or can arise spontaneously during development. The two genes associated with TSC are the TSC1 gene, which is on chromosome 9, and the TSC2 gene, found on chromosome 16. These genes code for the proteins hamartin and tuberin, which together help to regulate cell growth, proliferation, and differentiation. In people with TSC, a mutation in one of the two TSC genes interferes with the ability of cells to regulate these processes, allowing tumors and other abnormalities to develop in multiple organ systems.
To learn more about how TSC mutations cause the disorder and about how they can arise spontaneously or be passed from parent to offspring, see Cause.
Physicians practicing in the early nineteenth century described symptoms that are commonly associated with TSC today, but they didn't yet know what caused those symptoms. A French physician named Désiré-Magloire Bourneville was the first to connect symptoms such as seizures and cognitive disabilities with the abnormal brain anatomy now considered characteristic of TSC. In his research, first published in 1880, Bourneville examined the brain anatomy of three patients following their deaths. In life, all had suffered both seizures and severe cognitive impairment. In one patient in particular, Bourneville found a striking abnormality for which he coined the term tuberous sclerosis of the cerebral convolutions. This term described the firm, tuber-shaped growths, now called cortical tubers, that Bourneville found throughout the cerebral cortex of this individual. This discovery led to the first diagnosis of TSC.
It is no mistake that more than 125 years after Bourneville first described tuberous sclerosis, the name is still used to describe the disorder. Cortical tubers are found in most people with TSC. These abnormal growths arise early in brain development and become calcified and hardened, or sclerotic, over time. Of all the signs of TSC, tubers and other brain abnormalities are the disorder's most common manifestations. They are also some of the most serious clinical features of TSC, given that their presence is the likely cause of seizures, cognitive disabilities, and behavioral disorders.
To learn more about TSC diagnosis, see Diagnosis.