Tuberous sclerosis complex

Abstract

Tuberous sclerosis complex (TSC) is an inherit- ed autosomal dominant disorder characterized by generalized involvement and variable manifestations with a birth incidence of 1: 6000. Two responsible genes, TSC1 and TSC2, encode hamartin and tuberin, respectively. They were discovered in the 1990s and their functions were elucidated in the 2000s. Hamartin-tuberin complex is involved in the PI3K-AKT-mTOR signal transduction pathway and suppresses mTORCl activity. mTORCl is central to protein synthesis, cell proliferation, and autopha-gy. Consequently, constitutive activation of mTORCl results in variable manifestations of TSC, potentially including tumorigenesis, epilepsy, autism, and the appearance of white macules. Recently, genetic tests have been instituted to diagnose TSC. The number of TSC patients without neural symptoms is increasing, and in these individuals, renal and pulmonary lymphangioleiomyo-matosis are important manifestations. Because of these advances, new diagnostic criteria have been established, and new concepts such as TAND (TSC-associated neuropsychiatric disorders) and PEComa (perivascular epithelioid cell tumors) are being created. Further, mTORCl inhibitors are now being used to treat TSC patients. Although mTORCl inhibitors reduce the tumors, discontinuation of treatment permits regrowth of the tumors. For this reason, surgical treatment is also important. Plastic surgeons should be aware of the generalized symptoms when they conduct surgical treatments. This review contains a summary of recent advances and significant manifestations in TSC.