What is TSC?
First described in the 1880s by French neurologist Désiré-Magloire Bourneville, tuberous sclerosis complex (TSC) is a genetic disorder that causes tumors to form in many different organs, primarily in the brain, eyes, heart, kidney, skin and lungs. The aspects of TSC that most strongly impact quality of life are generally associated with the brain: seizures, developmental delay, intellectual disability and autism. However, many people with TSC are living independent, healthy lives and enjoying challenging professions such as doctors, lawyers, educators and researchers. The incidence and severity of the various aspects of TSC can vary widely between individuals—even between identical twins.
How Many People Have TSC?
At least two children born each day will have tuberous sclerosis complex. Current estimates place tuberous sclerosis complex-affected births at one in 6,000. Nearly 1 million people worldwide are estimated to have TSC, with approximately 50,000 in the United States. Many cases may remain undiagnosed for years or decades due to the relative obscurity of the disease and the mild form symptoms may take in some people.
How Does a Person Develop TSC?
Tuberous sclerosis complex is a genetic disease that can be inherited from one parent with TSC or can result from a spontaneous genetic mutation. Children have a 50 percent chance of inheriting TSC if one of their parents has this condition. At this point, only one-third of TSC cases are known to be inherited. The other two-thirds result from a spontaneous and unpredictable mutation occurring during conception or very early development of the human embryo.
What Genes are Responsible for TSC?
Two genes have been identified that can cause tuberous sclerosis complex. Only one of the genes needs to be affected for TSC to be present. The TSC1 gene is located on chromosome 9 and directs production of the protein called hamartin. The other gene, TSC2, is located on chromosome 16 and directs production of the protein called tuberin. Laboratory research on the function of these genes over the past decade has led to a new drug therapy for two types of tumors in TSC.
How Can So Many Different Organs Be Affected by TSC?
Both the TSC1 and TSC2 genes suppress tumor growth in the body by carefully regulating cell growth through inhibition of a protein called mechanistic target of rapamycin, or mTOR for short. When either the TSC1 or TSC2 gene is defective, cell growth is not adequately controlled and tuberous sclerosis complex results. Hamartin, tuberin, and mTOR are expressed in many different organs throughout the body, which explains why so many organs can be affected by TSC. However, researchers are still working diligently to figure out why TSC is manifested so differently between different people.
Are the Tumors Cancerous?
The growth of tumors resulting from tuberous sclerosis complex is not as severely unregulated as in cancer, but these tumors may still cause serious problems. Certain tumors, called subependymal giant cell astrocytomas, or SEGAs, can grow in the brain of people with TSC and may block the flow of cerebrospinal fluid in the spaces (ventricles) in the brain. This blockage can lead to behavioral changes, nausea, headaches or a number of other symptoms. In the heart, the tumors are usually at their largest at birth and then decrease in size as the individual gets older. These heart tumors, called cardiac rhabdomyomas, can cause problems at birth if they are blocking the flow of blood or causing severe abnormalities in the heart’s rhythm. Tumors in the eyes are not common but can present problems if they grow and block too much of the retina. The tumors in the kidney (renal angiomyolipomas) can become so large they eventually disrupt normal kidney function or begin to bleed internally. In the past, kidney failure was almost inevitable. Today, doctors can use drug therapy to shrink angiomyolipomas or can destroy individual tumors by embolization before they get too large and compromise healthy kidney tissue. In cases of severe pain or bleeding, angiomyolipomas can be removed by surgery. Renal cell carcinoma is very rare in TSC.
What Is the Normal Life Expectancy of an Individual with TSC?
Most people with TSC will live a normal life span. There can be complications in some organs such as the kidneys, lungs, and brain that can lead to severe difficulties and even death if left untreated. Uncontrolled epilepsy can also be life-threatening. To reduce these dangers, people with TSC should be monitored throughout their life by their physician for potential risks and complications. Thanks to research findings and improved medical therapies, people with tuberous sclerosis complex are experiencing better health care than ever before. But more research is needed until we find a cure.
Since There Is No Cure, What Can Be Done?
Early diagnosis and intervention can help overcome developmental delays. Data show that early seizure control in children can improve learning as compared to children without good seizure control. Advancements in research continue to bring new and improved therapeutic options. Some anti-seizure drugs can be effective in individuals with TSC. When drug treatment fails to adequately control seizures, technology can help identify the exact portions of the brain stimulating seizures to help decide if surgery may be a good approach in an individual.
For tumors in the brain, surgery is sometimes used to permanently remove tumors that are relatively few in number and easily accessible by the surgeon. In other cases, drug treatment may be used to shrink brain tumors. In the fall of 2010, the FDA approved the first drug with an indication specifically for TSC to treat a type of brain tumor known as subependymal giant cell astrocytomas (SEGAs). In 2012, the same drug was approved to treat growing angiomyolipomas, a type of kidney tumor in TSC, and in 2016, the same drug was approved as an add-on therapy to treat certain types of seizures associated with TSC.
Major advancements in treatments such as these require clinical studies to test the effectiveness of experimental drugs, surgery, or other interventions in people with TSC. Because the TSC community is in vital need of new treatments, individuals with TSC frequently volunteer to participate in cutting-edge clinical studies. Some ongoing clinical studies in TSC include testing the effects of very early drug treatment to fully or partially prevent epilepsy in infants with TSC, testing a new combination drug treatment for LAM, finding biomarkers to identify infants at high risk of developing autism or infantile spasms, and testing a topical drug treatment of facial angiofibromas. Thanks to volunteers in these and other studies, every new day brings us one step closer to finding improved treatments for TSC.