Department of Clinical Genetics and Cardiology and VASCERN HTAD European Reference Centre, Erasmus MC, University Medical Center Rotterdam, Wytemaweg 80, P.O. Box 2040, 3000 CA, Rotterdam, The Netherlands.
VASCERN HTAD European Reference Centre, Ghent, Belgium.
Orphanet J Rare Dis. 2019 Nov 21;14(1):264. doi: 10.1186/s13023-019-1186-2.
The ACTA2 gene encodes for smooth muscle specific α-actin, a critical component of the contractile apparatus of the vascular smooth muscle cell. Pathogenic variants in the ACTA2 gene are the most frequently encountered genetic cause of non-syndromic hereditary thoracic aortic disease (HTAD). Although thoracic aortic aneurysm and/or dissection is the main clinical manifestation, a variety of occlusive vascular disease and extravascular manifestations occur in ACTA2-related vasculopathy. Current data suggest possible mutation-specific manifestations of vascular and extra-aortic traits.Despite its relatively high prevalence, comprehensive recommendations on the care of patients and families with pathogenic variants in ACTA2 have not yet been established. We aimed to develop a consensus document to provide medical guidance for health care professionals involved in the diagnosis and treatment of patients and relatives with pathogenic variants in ACTA2.The HTAD Working Group of the European Reference Network for Rare Vascular Diseases (VASCERN) convened to review current literature and discuss expert opinions on clinical management of ACTA2 related vasculopathy. This consensus statement summarizes our recommendations on diagnosis, monitoring, treatment, pregnancy, genetic counselling and testing in patients with ACTA2-related vasculopathy. However, there is a clear need for additional prospective multicenter studies to further define proper guidelines.
ACTA2 基因编码平滑肌特异性 α-肌动蛋白，是血管平滑肌细胞收缩装置的关键组成部分。ACTA2 基因的致病性变体是最常遇到的非综合征性遗传性胸主动脉疾病（HTAD）的遗传原因。尽管胸主动脉瘤和/或夹层是主要的临床表现，但 ACTA2 相关血管病变会出现多种闭塞性血管疾病和血管外表现。目前的数据表明，血管和主动脉外特征可能存在特定的突变表现。尽管其患病率相对较高，但尚未制定针对 ACTA2 致病性变体患者和家属的护理综合建议。我们旨在制定一份共识文件，为参与 ACTA2 致病性变体患者和亲属诊断和治疗的医疗保健专业人员提供医疗指导。
欧洲罕见血管疾病参考网络（VASCERN）的 HTAD 工作组召开会议，审查了当前的文献，并就 ACTA2 相关血管病变的临床管理讨论了专家意见。本共识声明总结了我们对 ACTA2 相关血管病变患者的诊断、监测、治疗、妊娠、遗传咨询和检测的建议。然而，显然需要进行更多的前瞻性多中心研究，以进一步确定适当的指南。
