TY - JOUR
T1 - Expanding the genetic and phenotypic spectrum of ACTA2-related vasculopathies in a Dutch cohort
AU - van den Bersselaar, Lisa M.
AU - Verhagen, Judith M. A.
AU - Bekkers, Jos A.
AU - Kempers, Marlies
AU - Houweling, Arjan C.
AU - Baars, Marieke
AU - Overwater, Eline
AU - Hilhorst-Hofstee, Yvonne
AU - Barge-Schaapveld, Daniela Q. C. M.
AU - Rompen, Eline
AU - Krapels, Ingrid P. C.
AU - Dulfer, Eelco
AU - Wessels, Marja W.
AU - Loeys, Bart L.
AU - Verhagen, Hence J. M.
AU - Maugeri, Alessandra
AU - Roos-Hesselink, Jolien W.
AU - Brüggenwirth, Hennie T.
AU - van de Laar, Ingrid M. B. H.
N1 - Funding Information: 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
PY - 2022/10
Y1 - 2022/10
N2 - 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.
AB - 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.
KW - Aortic dissection
KW - Smooth muscle α-actin
KW - Thoracic aortic aneurysm
UR - http://www.scopus.com/inward/record.url?scp=85137724874&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.gim.2022.07.009
DO - https://doi.org/10.1016/j.gim.2022.07.009
M3 - Article
C2 - 36053285
SN - 1098-3600
VL - 24
SP - 2112
EP - 2122
JO - Genetics in medicine
JF - Genetics in medicine
IS - 10
ER -