Genetics of tuberous sclerosis complex: an update

Purpose To review the current genetic aspects of tuberous sclerosis complex. Methods Review of the literature. Results Tuberous sclerosis complex (TSC), a long known childhood-onset monogenic disorder, characterized by hamartoma formation affecting mainly the brain, heart, kidney, lung, and skin, is associated with a high morbidity burden and risk of a reduced life span. The identification of TSC1 and TSC2, as tumor suppressor genes causative of the disorder, led to the elucidation of the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway and its pivotal role in the pathogenesis of hamartoma formation. This knowledge was translated into standard clinical practice with the discovery of rapamycin, and additional analogues, as inhibitors of mTORC1. Conclusion Next-generation sequencing was proven to be fundamental to drive research of tumorigenesis in TSC, hopefully leading to new therapeutic options in the future.