Progress on genetics, diagnosis and treatment of tuberous sclerosis complex

Abstract

Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited disorder that variably affects multiple organs. It is caused by TSC1 or TSC2 gene variation and has a high genetic heterogeneity. The proteins encoded by TSC1 and TSC2 genes form a complex which mediate through the mechanistic target of rapamycin (mTOR), thereby inhibiting protein synthesis, meanwhile regulating neuronal migration and proliferation, axon formation and synaptic plasticity. TSC gene variation results in overreaction of mTOR pathway and leads to the occurrence of TSC. Based on studies of the pathogenesis of this disease, the diagnostic criteria of TSC was revised in 2012 by International Tuberous Sclerosis Complex Consensus Group, and gene diagnosis was added as an independent diagnostic criteria. Recently, a number of clinical trials of mTOR inhibitors have confirmed their efficacy in treatment of subependymal giant cell astrocytoma (SEGA), renal angiomyolipoma (AML) and refractory epilepsy of TSC.

DOI: 10.3969/j.issn.1672-6731.2018.06.002