Curatolo P, Maria B L
Department of Neuroscience, Pediatric Neurology Unit, Tor Vergata University of Rome, Rome, Italy.
Handb Clin Neurol. 2013;111:323-31. doi: 10.1016/B978-0-444-52891-9.00038-5.
Tuberous sclerosis complex (TSC) is a genetic multisystem disorder characterized by widespread hamartomas in several organs, including the brain, heart, skin, eyes, kidney, lung, and liver. The affected genes are TSC1 and TSC2, encoding hamartin and tuberin respectively. The hamartin-tuberin complex inhibits the mammalian-target-of-Rapamycin (mTOR) pathway, which controls cell growth and proliferation. Variations in the distribution, number, size, and location of lesions cause the clinical syndrome to vary even between relatives. About 85% of children and adolescents with TSC have CNS complications, including epilepsy, cognitive impairment, challenging behavioral problems, and autism-like symptoms. Epilepsy generally begins during the first year of life, with focal seizures and spasms. The discovery of the mTOR pathway upregulation in TSC-associated lesions presents new possibilities for treatment strategy. Increasing understanding of the molecular abnormalities caused by TSC may enable improved management of the disease.
结节性硬化症(TSC)是一种遗传性多系统疾病,其特征是在包括脑、心脏、皮肤、眼睛、肾脏、肺和肝脏在内的多个器官中广泛存在错构瘤。受影响的基因是TSC1和TSC2,分别编码错构瘤蛋白和结节蛋白。错构瘤蛋白-结节蛋白复合物抑制雷帕霉素哺乳动物靶点(mTOR)通路,该通路控制细胞生长和增殖。病变的分布、数量、大小和位置的变化导致临床综合征即使在亲属之间也有所不同。约85%的TSC儿童和青少年有中枢神经系统并发症,包括癫痫、认知障碍、具有挑战性的行为问题和自闭症样症状。癫痫通常在生命的第一年开始,表现为局灶性发作和痉挛。TSC相关病变中mTOR通路上调的发现为治疗策略带来了新的可能性。对TSC引起的分子异常的进一步了解可能有助于改善该疾病的管理。