Today, families who want to identify which mutation caused tuberous sclerosis complex (TSC) in their child or other family member can pursue DNA testing of the two known TSC genes. These genes (TSC1 and TSC2) are involved in approximately 70 percent of TSC diagnoses. This means that when we look at the TSC1 and TSC2 genes in persons with a clear diagnosis of TSC, we find a mutation in one gene or the other (not in both) about 70 percent of the time. It is still unclear where the mutation lies in the remaining 30 percent of people tested.
DNA testing is conducted on a blood sample.
Because people can have TSC and not have an identifiable mutation, the DNA test for TSC is not diagnostic, meaning it cannot be used to make the diagnosis in a person with questionable physical findings. However, it can be used to test other family members with questionable symptoms of TSC, or for prenatal diagnosis in persons who have TSC or who are concerned about recurrence due to germline mosaicism. Such testing can be performed only after the mutation has been found in the family member with a definite diagnosis of TSC.
Despite advancing knowledge about TSC mutations, we still cannot predict the severity of physical symptoms in a person with a new diagnosis of TSC. A person can have TSC and have very few or mild symptoms, while a family member with TSC can have more severe or extensive symptoms. It is thought, however, that most people who have a TSC mutation (excluding persons with germline mosaicism) will have some signs or symptoms if examined carefully by a physician familiar with the diagnosis of TSC. The distinction between sporadic TSC and familial (or inherited) TSC is important, as it affects the chance for other people in the family to be affected. Therefore, immediate family members of a person newly diagnosed with TSC should be thoroughly examined.