Genetic Screening in Heritable Thoracic Aortic Disease-rationale, Potentials and Pitfalls

Overview

Journal Indian J Thorac Cardiovasc Surg

Publisher Springer

Date 2022 Apr 25

PMID 35463717

Authors

Metesh Acharya

Daniele Maselli

Giovanni Mariscalco

Affiliations

Soon will be listed here.

Abstract

Thoracic aortic aneurysms are silent yet deadly clinical entities which may elude detection until an acutely life-threatening aortic dissection or rupture occurs. Approximately 20% of patients with thoracic aortic aneurysms or dissection have a positive family history, indicating a strong genetic component to the aetiology. Genetic screening in such hereditary thoracic aortic disease (HTAD) may thus be beneficial in detecting causative genetic mutations in affected patients, identifying asymptomatic family members who may be at risk, and in guiding the optimal timing of preventative surgery in those with confirmed genetic aortopathy. Genetic screening can facilitate personalised aortic care tailored to an individual's specific genetic abnormality, with the aim of mitigating the significant morbidity burden and premature mortality associated with HTAD. This review examines the rationale for genetic screening in HTAD, its potential applications, current limitations and potential future directions.

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References

Loeys B, Schwarze U, Holm T, Callewaert B, Thomas G, Pannu H . Aneurysm syndromes caused by mutations in the TGF-beta receptor. N Engl J Med. 2006; 355(8):788-98. DOI: 10.1056/NEJMoa055695. View

Renard M, Francis C, Ghosh R, Scott A, Witmer P, Ades L . Clinical Validity of Genes for Heritable Thoracic Aortic Aneurysm and Dissection. J Am Coll Cardiol. 2018; 72(6):605-615. PMC: 6378369. DOI: 10.1016/j.jacc.2018.04.089. View

Chou A, Ma W, Mok S, Ziganshin B, Peterss S, Rizzo J . Do Familial Aortic Dissections Tend to Occur at the Same Age?. Ann Thorac Surg. 2016; 103(2):546-550. DOI: 10.1016/j.athoracsur.2016.06.007. View

Stheneur C, Collod-Beroud G, Faivre L, Buyck J, Gouya L, Le Parc J . Identification of the minimal combination of clinical features in probands for efficient mutation detection in the FBN1 gene. Eur J Hum Genet. 2009; 17(9):1121-8. PMC: 2986588. DOI: 10.1038/ejhg.2009.36. View

Campens L, Renard M, Callewaert B, Coucke P, De Backer J, De Paepe A . New insights into the molecular diagnosis and management of heritable thoracic aortic aneurysms and dissections. Pol Arch Med Wewn. 2013; 123(12):693-700. DOI: 10.20452/pamw.2015. View

Goyal A, Keramati A, Czarny M, Resar J, Mani A . The Genetics of Aortopathies in Clinical Cardiology. Clin Med Insights Cardiol. 2017; 11:1179546817709787. PMC: 5457142. DOI: 10.1177/1179546817709787. View

Loeys B, Chen J, Neptune E, Judge D, Podowski M, Holm T . A syndrome of altered cardiovascular, craniofacial, neurocognitive and skeletal development caused by mutations in TGFBR1 or TGFBR2. Nat Genet. 2005; 37(3):275-81. DOI: 10.1038/ng1511. View

Milewicz D, Chen H, Park E, Petty E, Zaghi H, Shashidhar G . Reduced penetrance and variable expressivity of familial thoracic aortic aneurysms/dissections. Am J Cardiol. 1998; 82(4):474-9. DOI: 10.1016/s0002-9149(98)00364-6. View

Elefteriades J, Farkas E . Thoracic aortic aneurysm clinically pertinent controversies and uncertainties. J Am Coll Cardiol. 2010; 55(9):841-57. DOI: 10.1016/j.jacc.2009.08.084. View

10.

Lawal T, Lewis K, Johnston J, Heidlebaugh A, Ng D, Gaston-Johansson F . Disclosure of cardiac variants of uncertain significance results in an exome cohort. Clin Genet. 2018; 93(5):1022-1029. PMC: 5961741. DOI: 10.1111/cge.13220. View

11.

Elefteriades J, Ziganshin B . Paradigm for Detecting Silent Thoracic Aneurysm Disease. Semin Thorac Cardiovasc Surg. 2017; 28(4):776-782. DOI: 10.1053/j.semtcvs.2016.10.006. View

12.

Albornoz G, Coady M, Roberts M, Davies R, Tranquilli M, Rizzo J . Familial thoracic aortic aneurysms and dissections--incidence, modes of inheritance, and phenotypic patterns. Ann Thorac Surg. 2006; 82(4):1400-5. DOI: 10.1016/j.athoracsur.2006.04.098. View

13.

Montgomery R, Geraghty M, Bull E, Gelb B, Johnson M, McIntosh I . Multiple molecular mechanisms underlying subdiagnostic variants of Marfan syndrome. Am J Hum Genet. 1998; 63(6):1703-11. PMC: 1377642. DOI: 10.1086/302144. View

14.

Pape L, Tsai T, Isselbacher E, Oh J, OGara P, Evangelista A . Aortic diameter >or = 5.5 cm is not a good predictor of type A aortic dissection: observations from the International Registry of Acute Aortic Dissection (IRAD). Circulation. 2007; 116(10):1120-7. DOI: 10.1161/CIRCULATIONAHA.107.702720. View

15.

Brownstein A, Ziganshin B, Elefteriades J . Human aortic aneurysm genomic dictionary: is it possible?. Indian J Thorac Cardiovasc Surg. 2020; 35(Suppl 2):57-66. PMC: 7525885. DOI: 10.1007/s12055-018-0659-6. View

16.

Boodhwani M, Andelfinger G, Leipsic J, Lindsay T, McMurtry M, Therrien J . Canadian Cardiovascular Society position statement on the management of thoracic aortic disease. Can J Cardiol. 2014; 30(6):577-89. DOI: 10.1016/j.cjca.2014.02.018. View

17.

Zhu L, Vranckx R, Khau Van Kien P, Lalande A, Boisset N, Mathieu F . Mutations in myosin heavy chain 11 cause a syndrome associating thoracic aortic aneurysm/aortic dissection and patent ductus arteriosus. Nat Genet. 2006; 38(3):343-9. DOI: 10.1038/ng1721. View

18.

Ziganshin B, Bailey A, Coons C, Dykas D, Charilaou P, Tanriverdi L . Routine Genetic Testing for Thoracic Aortic Aneurysm and Dissection in a Clinical Setting. Ann Thorac Surg. 2015; 100(5):1604-11. DOI: 10.1016/j.athoracsur.2015.04.106. View

19.

Carino D, Agostinelli A, Molardi A, Benassi F, Gherli T, Nicolini F . The role of genetic testing in the prevention of acute aortic dissection. Eur J Prev Cardiol. 2018; 25(1_suppl):15-23. DOI: 10.1177/2047487318756433. View

20.

Guo D, Pannu H, Tran-Fadulu V, Papke C, Yu R, Avidan N . Mutations in smooth muscle alpha-actin (ACTA2) lead to thoracic aortic aneurysms and dissections. Nat Genet. 2007; 39(12):1488-93. DOI: 10.1038/ng.2007.6. View