Genetics

TSC is inherited as an autosomal dominant trait with variable penetrance. This means that for each child born to a parent with TSC, there is a 50% chance that child will have TSC, and that the clinical manifestations present in that child can be highly variable and different from those observed in the parent.

Estimates of the rate of spontaneous mutation vary from 56% to 86% depending in part on the completeness of investigation of the extended family. The clinical findings may vary within the same family, where the child with tuberous sclerosis complex will be more severely affected than the parent with TSC. Occasionally, couples with two or more affected children have been seen who have no other evidence of TSC, even after a thorough clinical investigation.

Thus, clinical diagnosis of individuals with few clinical findings can be difficult.

Genetic linkage studies have shown that there are two tuberous sclerosis complex genes, one on chromosome 9 (TSCI gene) and one on chromosome 16 (TSC2 gene), with approximately one-half of the families used in genetic linkage studies having the TSC1 gene, and the other one-half with the TSC2 gene.

The disease can now be diagnosed by its clinical manifestations on the skin, eyes, brain, kidneys, or in other organs as well as through genetic testing.