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.
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.
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.
Although most people with TSC have tubers and may develop other abnormal growths in the brain and other organs, fortunately many are mildly affected and lead full and productive lives. Early diagnosis, followed by careful monitoring of and intervention in the medical condition of individuals with TSC is key to a positive outcome. Recent advances in imaging technology have made it possible for physicians to track the progress of internal TSC-related lesions and to intervene before abnormalities can cause significant problems. Specialists also successfully treat a wide range of many of the disorder's symptoms, including seizures, behavioral disorders, and various skin abnormalities.
It's not known whether all of this research will ultimately produce a cure for TSC. However, it is certain that the tireless work of physicians and scientists who study TSC will lead to continued improvements in the lives of people with the disorder.
It is important to remember:
- TSC is a genetic disorder that causes benign tumors and other abnormalities to develop in all major organ systems
- Symptoms vary widely from one individual to the next and typically change over time
- TSC is seen in approximately 1 in every 6,000 individuals, regardless of race, ethnicity, or gender
- TSC is caused by a permanent change, or mutation, in one of two genes, TSC1 or TSC2, that may be passed from parent to offspring or arise spontaneously during development
- TSC mutations interfere with the ability of cells to regulate cell growth, proliferation, and differentiation
- The disorder was first described in detail in 1880, based on neurological findings and brain abnormalities called cortical tubers
- Cortical tubers are firm, tuber-shaped growths that are found in the cerebral cortex of most people with TSC and are thought to cause symptoms such as seizures, cognitive dysfunction, and behavioral disorders
- Despite a wide range of symptoms common to TSC, most people with the disorder experience normal life expectancy
- Early diagnosis and intervention is the best way to minimize and manage symptoms of TSC
- Researchers are exploring both new ways to treat and possibly cure TSC