TSC exhibits an autosomal dominant inheritance pattern with a high spontaneous mutation rate. About two thirds of TSC cases are sporadic, the other one third is familial.
Two distinct genes for TSC have been identified: one on chromosome 9q34 (TSC1) and another on chromosome 16p13 (TSC2). TSC2 gene (also known as tuberin) was identified in 1993. TSC1 gene (also known as hamartin) was identified more recently, in 1997.
Approximately 50% of TSC families show genetic linkage to TSC1 and 50% to TSC2. However among sporadic TSC cases, mutations in TSC2 are five times more frequent. Currently, there is little information on how a mutation in TSC1 or 2 could result in clinical presentations and how severe these may be.