Vascular Ehlers-Danlos Syndrome: A Comprehensive Natural History Study in a Dutch National Cohort of 142 Patients

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 TintelenMarsha Voorendt, Vivian de Waard, Alessandra Maugeri, Hennie T. Brüggenwirth, Ingrid M.B.H. van de Laar, Arjan C. Houweling

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

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 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.

Original languageEnglish
Article numbere003978
JournalCirculation: Genomic and Precision Medicine
Volume17
Issue number3
DOIs
Publication statusPublished - 16 Apr 2024

Bibliographical note

Publisher Copyright:
© 2024 The Authors. Circulation: Genomic and Precision Medicine is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.

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