Division of Vascular Surgery, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Thoracic Aortic Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
Am J Med Genet C Semin Med Genet. 2020 Mar;184(1):136-148. doi: 10.1002/ajmg.c.31771. Epub 2020 Feb 8.
Aortopathies encompass a variety of inherited and acquired pathologies that increase risk of life-threatening dissection or rupture. Identifying individuals with hereditary thoracic aortic aneurysm and dissection (HTAAD) for longitudinal monitoring, medical therapy, or elective and preventative repair is paramount to reduce risk of cardiovascular-related mortality and complications from dissection and rupture. Over the past couple of decades, pathogenic variants in numerous genes have been identified in relation to HTAAD. The genetic diagnosis can help stratify patient risk and provide guidance on medical treatment, timing of prophylactic surgical repair, as well as longitudinal surveillance and imaging. Implicated genes and their associated proteins have been found to act on a diverse variety of pathways, cells and structural components linked to transforming growth factor beta (TGF-β) signaling pathways, disruption of the vascular smooth muscle cell contractile apparatus, and primary disruption of extracellular matrix homeostasis. This review describes relevant genetic variants that may help identify and guide the management of hereditary thoracic aortic aneurysms and dissections.
主动脉病变包括多种遗传性和获得性病变，会增加危及生命的夹层或破裂风险。确定具有遗传性胸主动脉瘤和夹层（HTAAD）的个体进行纵向监测、药物治疗、或选择性和预防性修复对于降低心血管相关死亡率以及夹层和破裂并发症的风险至关重要。在过去的几十年中，已经确定了与 HTAAD 相关的许多基因中的致病性变异。遗传诊断有助于对患者的风险进行分层，并为药物治疗、预防性手术修复的时机以及纵向监测和影像学检查提供指导。已发现相关基因及其相关蛋白作用于多种途径、细胞和结构成分，这些都与转化生长因子-β（TGF-β）信号通路、血管平滑肌细胞收缩装置的破坏以及细胞外基质稳态的原发性破坏有关。本文综述了有助于识别和指导遗传性胸主动脉瘤和夹层管理的相关遗传变异。
