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A highly penetrant ACTA2 mutation of thoracic aortic disease
BACKGROUND: The role of ACTA2 mutations in Familial Aortic Disease has been increasingly recognized. We describe a highly penetrant variant (R118Q) in a family with aortic disease. CASE REPORT: A patient presented to us for elective repair of an ascending aortic aneurysm with a family history of his...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694883/ https://www.ncbi.nlm.nih.gov/pubmed/38044429 http://dx.doi.org/10.1186/s13019-023-02420-0 |
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author | Bobba, Christopher M. Azarrafiy, Ryan Spratt, John R. Hendrickson, Jill Martin, Tomas D. Arnaoutakis, George J. Jeng, Eric I. Beaver, Thomas M. |
author_facet | Bobba, Christopher M. Azarrafiy, Ryan Spratt, John R. Hendrickson, Jill Martin, Tomas D. Arnaoutakis, George J. Jeng, Eric I. Beaver, Thomas M. |
author_sort | Bobba, Christopher M. |
collection | PubMed |
description | BACKGROUND: The role of ACTA2 mutations in Familial Aortic Disease has been increasingly recognized. We describe a highly penetrant variant (R118Q) in a family with aortic disease. CASE REPORT: A patient presented to us for elective repair of an ascending aortic aneurysm with a family history of his mother expiring after aortic dissection. Genetic testing revealed he was a heterozygous carrier of the ACTA2 missense mutation R118Q. Subsequently, all living family members were tested for this variant and a full medical history was obtained to compile a family tree for the variant and penetrance of an aortic event (defined as lifetime occurrence of aortic surgery / dissection). In total 9 family members were identified and underwent genetic testing with 7/9 showing presence of the ACTA2 R118Q mutation or an aortic event. All patients over the age of 50 (n = 4) had an aortic event. Those events occurred at ages 54, 55, 60, and 62 (mean event at 57.8 ± 3.9 years). Three family members with the variant under the age of 40 have not had an aortic event and most are undergoing regular aortic surveillance via CT scan. CONCLUSIONS: Existing studies of known ACTA2 mutations describe a 76% aortic event rate by 85 years old. The R118Q missense mutation is a less common ACTA2 variant, estimated to be found in about 5% of patients with known mutations. Prior studies have predicted the R118Q mutation to have a slightly decreased risk of aortic events compared to other ACTA2 mutations. In this family, however, we demonstrate 100% penetrance of aortic disease above age 50. In today’s era of excellent outcomes in elective aortic surgery, our team aggressively offers elective repair. We advocate for strict aortic surveillance for patients with this variant and would consider elective aortic replacement at 4.5 cm, or at an even smaller diameter in patients with a strong family history of dissection who are identified with this mutation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13019-023-02420-0. |
format | Online Article Text |
id | pubmed-10694883 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-106948832023-12-05 A highly penetrant ACTA2 mutation of thoracic aortic disease Bobba, Christopher M. Azarrafiy, Ryan Spratt, John R. Hendrickson, Jill Martin, Tomas D. Arnaoutakis, George J. Jeng, Eric I. Beaver, Thomas M. J Cardiothorac Surg Case Report BACKGROUND: The role of ACTA2 mutations in Familial Aortic Disease has been increasingly recognized. We describe a highly penetrant variant (R118Q) in a family with aortic disease. CASE REPORT: A patient presented to us for elective repair of an ascending aortic aneurysm with a family history of his mother expiring after aortic dissection. Genetic testing revealed he was a heterozygous carrier of the ACTA2 missense mutation R118Q. Subsequently, all living family members were tested for this variant and a full medical history was obtained to compile a family tree for the variant and penetrance of an aortic event (defined as lifetime occurrence of aortic surgery / dissection). In total 9 family members were identified and underwent genetic testing with 7/9 showing presence of the ACTA2 R118Q mutation or an aortic event. All patients over the age of 50 (n = 4) had an aortic event. Those events occurred at ages 54, 55, 60, and 62 (mean event at 57.8 ± 3.9 years). Three family members with the variant under the age of 40 have not had an aortic event and most are undergoing regular aortic surveillance via CT scan. CONCLUSIONS: Existing studies of known ACTA2 mutations describe a 76% aortic event rate by 85 years old. The R118Q missense mutation is a less common ACTA2 variant, estimated to be found in about 5% of patients with known mutations. Prior studies have predicted the R118Q mutation to have a slightly decreased risk of aortic events compared to other ACTA2 mutations. In this family, however, we demonstrate 100% penetrance of aortic disease above age 50. In today’s era of excellent outcomes in elective aortic surgery, our team aggressively offers elective repair. We advocate for strict aortic surveillance for patients with this variant and would consider elective aortic replacement at 4.5 cm, or at an even smaller diameter in patients with a strong family history of dissection who are identified with this mutation. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13019-023-02420-0. BioMed Central 2023-12-04 /pmc/articles/PMC10694883/ /pubmed/38044429 http://dx.doi.org/10.1186/s13019-023-02420-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Case Report Bobba, Christopher M. Azarrafiy, Ryan Spratt, John R. Hendrickson, Jill Martin, Tomas D. Arnaoutakis, George J. Jeng, Eric I. Beaver, Thomas M. A highly penetrant ACTA2 mutation of thoracic aortic disease |
title | A highly penetrant ACTA2 mutation of thoracic aortic disease |
title_full | A highly penetrant ACTA2 mutation of thoracic aortic disease |
title_fullStr | A highly penetrant ACTA2 mutation of thoracic aortic disease |
title_full_unstemmed | A highly penetrant ACTA2 mutation of thoracic aortic disease |
title_short | A highly penetrant ACTA2 mutation of thoracic aortic disease |
title_sort | highly penetrant acta2 mutation of thoracic aortic disease |
topic | Case Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10694883/ https://www.ncbi.nlm.nih.gov/pubmed/38044429 http://dx.doi.org/10.1186/s13019-023-02420-0 |
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