血管性埃勒斯-丹洛斯综合征:荷兰全国 142 例患者的综合自然史研究

IF 6 2区 医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Circulation: Genomic and Precision Medicine Pub Date : 2024-04-16 DOI:10.1161/circgen.122.003978
Serwet Demirdas, Lisa M. van den Bersselaar, Rosan Lechner, Jessica Bos, Suzanne I.M. Alsters, Marieke J.H. Baars, Annette F. Baas, Özlem Baysal, Saskia N. van der Crabben, Eelco Dulfer, Noor A.A. Giesbertz, Apollonia T.J.M. Helderman-van den Enden, Yvonne Hilhorst-Hofstee, Marlies J.E. Kempers, Fenne L. Komdeur, Bart Loeys, Daniëlle Majoor-Krakauer, Charlotte W. Ockeloen, Eline Overwater, Peter J. van Tintelen, Marsha Voorendt, Vivian de Waard, Alessandra Maugeri, Hennie T. Brüggenwirth, Ingrid M.B.H. van de Laar, Arjan C. Houweling
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引用次数: 0

摘要

背景:血管性埃勒斯-丹洛斯综合征(vEDS)是一种罕见的结缔组织疾病,具有动脉、肠道和子宫破裂的高风险,由COL3A1的杂合致病变异引起。这项队列研究旨在进一步了解 vEDS 的自然史,并描述荷兰多中心队列中基因型与表型的相关性,以优化患者护理并提高对该疾病的认识。结果:共有 142 人(50% 为女性)参与了研究,其中包括 46 名指数患者(32%)。基因诊断时的总体中位年龄为 41.0 岁。半数以上的指数患者(54.3%)和亲属(53.1%)的体征高度提示vEDS。在这些人中,重大事件发生的频率并不高(P=0.90),但发生的年龄较小(P=0.01)。与女性相比,男性发生重大事件的频率更高,年龄更小(分别为 P<0.001 和 P=0.004)。主动脉瘤(P=0.003)和气胸(P=0.029)在男性中更为常见。结论:男性性别、COL3A1变体的类型和位置以及高度提示vEDS的体貌特征是导致重大事件发生和/或发病年龄提前的风险因素。这项针对荷兰vEDS患者的全国性多中心队列研究为改进vEDS患者的诊断、随访和治疗指南提供了宝贵的依据。
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Vascular Ehlers-Danlos Syndrome: A Comprehensive Natural History Study in a Dutch National Cohort of 142 Patients
BACKGROUND:Vascular Ehlers-Danlos syndrome (vEDS) is a rare connective tissue disorder with a high risk for arterial, bowel, and uterine rupture, caused by heterozygous pathogenic variants in COL3A1. The aim of this cohort study is to provide further insights into the natural history of vEDS and describe genotype-phenotype correlations in a Dutch multicenter cohort to optimize patient care and increase awareness of the disease.METHODS:Individuals with vEDS throughout the Netherlands were included. The phenotype was charted by retrospective analysis of molecular and clinical data, combined with a one-time physical examination.RESULTS:A total of 142 individuals (50% female) participated the study, including 46 index patients (32%). The overall median age at genetic diagnosis was 41.0 years. More than half of the index patients (54.3%) and relatives (53.1%) had a physical appearance highly suggestive of vEDS. In these individuals, major events were not more frequent (P=0.90), but occurred at a younger age (P=0.01). A major event occurred more often and at a younger age in men compared with women (P<0.001 and P=0.004, respectively). Aortic aneurysms (P=0.003) and pneumothoraces (P=0.029) were more frequent in men. Aortic dissection was more frequent in individuals with a COL3A1 variant in the first quarter of the collagen helical domain (P=0.03).CONCLUSIONS:Male sex, type and location of the COL3A1 variant, and physical appearance highly suggestive of vEDS are risk factors for the occurrence and/or early age of onset of major events. This national multicenter cohort study of Dutch individuals with vEDS provides a valuable basis for improving guidelines for the diagnosing, follow-up, and treatment of individuals with vEDS.
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来源期刊
Circulation: Genomic and Precision Medicine
Circulation: Genomic and Precision Medicine Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
9.20
自引率
5.40%
发文量
144
期刊介绍: Circulation: Genomic and Precision Medicine is a distinguished journal dedicated to advancing the frontiers of cardiovascular genomics and precision medicine. It publishes a diverse array of original research articles that delve into the genetic and molecular underpinnings of cardiovascular diseases. The journal's scope is broad, encompassing studies from human subjects to laboratory models, and from in vitro experiments to computational simulations. Circulation: Genomic and Precision Medicine is committed to publishing studies that have direct relevance to human cardiovascular biology and disease, with the ultimate goal of improving patient care and outcomes. The journal serves as a platform for researchers to share their groundbreaking work, fostering collaboration and innovation in the field of cardiovascular genomics and precision medicine.
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