Wataya-Kaneda Mari, Uemura Motohide, Fujita Kazutoshi, Hirata Haruhiko, Osuga Keigo, Kagitani-Shimono Kuriko, Nonomura Norio
Department of Dermatology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Department of Urology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan.
Int J Urol. 2017 Sep;24(9):681-691. doi: 10.1111/iju.13390. Epub 2017 Jul 1.
Tuberous sclerosis complex is an autosomal dominant inherited disorder characterized by generalized involvement and variable manifestations with a birth incidence of 1:6000. In a quarter of a century, significant progress in tuberous sclerosis complex has been made. Two responsible genes, TSC1 and TSC2, which encode hamartin and tuberin, respectively, were discovered in the 1990s, and their functions were elucidated in the 2000s. Hamartin-Tuberin complex is involved in the phosphoinositide 3-kinase-protein kinase B-mammalian target of rapamycin signal transduction pathway, and suppresses mammalian target of rapamycin complex 1 activity, which is a center for various functions. Constitutive activation of mammalian target of rapamycin complex 1 causes variable manifestations in tuberous sclerosis complex. Recently, genetic tests were launched to diagnose tuberous sclerosis complex, and mammalian target of rapamycin complex 1 inhibitors are being used to treat tuberous sclerosis complex patients. As a result of these advances, new diagnostic criteria have been established and an indispensable new treatment method; that is, "a cross-sectional medical examination system," a system to involve many experts for tuberous sclerosis complex diagnosis and treatments, was also created. Simultaneously, the frequency of genetic tests and advances in diagnostic technology have resulted in new views on symptoms. The numbers of tuberous sclerosis complex patients without neural symptoms are increasing, and for these patients, renal manifestations and pulmonary lymphangioleiomyomatosis have become important manifestations. New concepts of tuberous sclerosis complex-associated neuropsychiatric disorders or perivascular epithelioid cell tumors are being created. The present review contains a summary of recent advances, significant manifestations and therapy in tuberous sclerosis complex.
结节性硬化症是一种常染色体显性遗传性疾病，其特征为全身受累且表现多样，出生发病率为1:6000。在四分之一个世纪里，结节性硬化症取得了重大进展。20世纪90年代发现了两个致病基因，即TSC1和TSC2，它们分别编码错构瘤蛋白和结节蛋白，其功能在21世纪得以阐明。错构瘤蛋白 - 结节蛋白复合物参与磷酸肌醇3激酶 - 蛋白激酶B - 雷帕霉素哺乳动物靶标信号转导通路，并抑制雷帕霉素哺乳动物靶标复合物1的活性，该复合物是多种功能的核心。雷帕霉素哺乳动物靶标复合物1的组成性激活导致结节性硬化症出现多样表现。最近，开展了基因检测以诊断结节性硬化症，并且雷帕霉素哺乳动物靶标复合物1抑制剂正用于治疗结节性硬化症患者。由于这些进展，已经建立了新的诊断标准，还创建了一种不可或缺的新治疗方法，即“横断面医学检查系统”，这是一种让许多专家参与结节性硬化症诊断和治疗的系统。同时，基因检测的频率和诊断技术的进步导致了对症状的新认识。无神经症状的结节性硬化症患者数量正在增加，对于这些患者，肾脏表现和肺淋巴管平滑肌瘤病已成为重要表现。与结节性硬化症相关的神经精神疾病或血管周围上皮样细胞瘤的新概念正在形成。本综述总结了结节性硬化症的近期进展、重要表现和治疗方法。
