TSC affects multiple organs throughout the lifetime. Both the TSC1 and TSC2 genes hold the instructions for creating proteins called hamartin and tuberin, respectively. These proteins form a complex (essentially a protein sandwich) that works in a delicate biochemical pathway. This pathway is called the mTOR pathway, where mTOR stands for “mechanistic target of rapamycin.” The pathway carefully regulates cell growth in almost every cell type in the body. The TSC1 and TSC2 proteins, when functioning together properly, regulate a key step in this pathway and suppress tumor growth.
When either the TSC1 or TSC2 gene mutates, cell growth cannot be adequately controlled, which leads to TSC. Hamartin, tuberin, and mTOR are expressed in many different cells 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 manifests so differently between different people.
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. Researchers estimate that 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. To learn more about the mTOR pathway and genetics click here for the Primer course available in TSC Academy.