Expanding the genetic and phenotypic spectrum of ACTA2-related vasculopathies in a Dutch cohort

Lisa M. van den Bersselaar, Judith M.A. Verhagen, Jos A. Bekkers, Marlies Kempers, Arjan C. Houweling, Marieke Baars, Eline Overwater, Yvonne Hilhorst-Hofstee, Daniela Q.C.M. Barge-Schaapveld, Eline Rompen, Ingrid P.C. Krapels, Eelco Dulfer, Marja W. Wessels, Bart L. Loeys, Hence J.M. Verhagen, Alessandra Maugeri, Jolien W. Roos-Hesselink, Hennie T. Brüggenwirth, Ingrid M.B.H. van de Laar*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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PURPOSE: Heterozygous pathogenic/likely pathogenic (P/LP) variants in the ACTA2 gene confer a high risk for thoracic aortic aneurysms and aortic dissections. This retrospective multicenter study elucidates the clinical outcome of ACTA2-related vasculopathies.

METHODS: Index patients and relatives with a P/LP variant in ACTA2 were included. Data were collected through retrospective review of medical records using a standardized questionnaire.

RESULTS: A total of 49 individuals from 28 families participated in our study. In total, 20 different ACTA2 variants were detected. Aortic events occurred in 65% of the cases (78.6% index patients and 47.6% relatives). Male sex and hypertension emerged as significantly associated with aortic events. Of 20 individuals, 5 had an aortic diameter of <45 mm (1.77 inches) at the time of the type A dissection. Mean age at first aortic event was 49.0 ± 12.4 years. Severe surgical complications for type A and type B dissection occurred in 25% and 16.7% of the cases and in-hospital mortality rates were 9.5% and 0%, respectively.

CONCLUSION: P/LP ACTA2 variants are associated with an increased risk for an aortic event and age-related penetrance, which emphasizes the importance of early recognition of the disease. Caregivers should be aware of the risk for aortic dissections, even in individuals with aortic diameters within the normal range.

Original languageEnglish
Pages (from-to)2112-2122
Number of pages11
JournalGenetics in Medicine
Issue number10
Publication statusPublished - Oct 2022

Bibliographical note

We would like to thank all the research participants and the physicians and genetic counselors and investigators who
have included individuals in this study and collected clinical data. This work was supported by the Dutch Heart Foundation (2014T007).

Publisher Copyright: © 2022 The Authors


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