Valvulopathies and Genetics: Where Are We?

Overview

Journal Rev Cardiovasc Med

Specialty Cardiology & Vascular Diseases

Date 2024 Jul 30

PMID 39077344

Authors

Monica Coll

Anna Fernandez-Falgueras

Anna Iglesias

Ramon Brugada

Affiliations

Soon will be listed here.

Abstract

Valvulopathies are among the most common cardiovascular diseases, significantly increasing morbidity and mortality. While many valvular heart diseases are acquired later in life, an important genetic component has been described, particularly in mitral valve prolapse and bicuspid aortic valve. These conditions can arise secondary to genetic syndromes such as Marfan disease (associated with mitral valve prolapse) or Turner syndrome (linked to the bicuspid aortic valve) or may manifest in a non-syndromic form. When cardiac valve disease is the primary cause, it can appear in a familial clustering or sporadically, with a clear genetic component. The identification of new genes, regulatory elements, post-transcriptional modifications, and molecular pathways is crucial to identify at-risk familial carriers and for developing novel therapeutic strategies. In the present review we will discuss the numerous genetic contributors of heart valve diseases.

Citing Articles

Role of miRNAs in Regulating Ascending Aortic Dilation in Bicuspid Aortic Valve Patients Operated for Aortic Stenosis.

Sanchez-Garcia A, Soule-Egea M, Fuentevilla-Alvarez G, Vargas-Alarcon G, Hernandez-Mejia B, Martinez-Hernandez H Int J Mol Sci. 2025; 26(2).

PMID: 39859493 PMC: 11765635. DOI: 10.3390/ijms26020779.

References

Gould R, Aziz H, Woods C, Seman-Senderos M, Sparks E, Preuss C . ROBO4 variants predispose individuals to bicuspid aortic valve and thoracic aortic aneurysm. Nat Genet. 2018; 51(1):42-50. PMC: 6309588. DOI: 10.1038/s41588-018-0265-y. View

Harb S, Griffin B . Mitral Valve Disease: a Comprehensive Review. Curr Cardiol Rep. 2017; 19(8):73. DOI: 10.1007/s11886-017-0883-5. View

Peters A, Duggan J, Trachiotis G, Antevil J . Epidemiology of Valvular Heart Disease. Surg Clin North Am. 2022; 102(3):517-528. DOI: 10.1016/j.suc.2022.01.008. View

Durst R, Sauls K, Peal D, deVlaming A, Toomer K, Leyne M . Mutations in DCHS1 cause mitral valve prolapse. Nature. 2015; 525(7567):109-13. PMC: 4720389. DOI: 10.1038/nature14670. View

Kyndt F, Schott J, Trochu J, Baranger F, Herbert O, Scott V . Mapping of X-linked myxomatous valvular dystrophy to chromosome Xq28. Am J Hum Genet. 1998; 62(3):627-32. PMC: 1376942. DOI: 10.1086/301747. View

Benson D, Silberbach G, Kavanaugh-McHugh A, Cottrill C, Zhang Y, Riggs S . Mutations in the cardiac transcription factor NKX2.5 affect diverse cardiac developmental pathways. J Clin Invest. 1999; 104(11):1567-73. PMC: 409866. DOI: 10.1172/JCI8154. View

John A, McDonald-McGinn D, Zackai E, Goldmuntz E . Aortic root dilation in patients with 22q11.2 deletion syndrome. Am J Med Genet A. 2009; 149A(5):939-42. PMC: 4080309. DOI: 10.1002/ajmg.a.32770. View

Siu S, Silversides C . Bicuspid aortic valve disease. J Am Coll Cardiol. 2010; 55(25):2789-800. DOI: 10.1016/j.jacc.2009.12.068. View

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

10.

Liang Q, de Windt L, Witt S, Kimball T, Markham B, Molkentin J . The transcription factors GATA4 and GATA6 regulate cardiomyocyte hypertrophy in vitro and in vivo. J Biol Chem. 2001; 276(32):30245-53. DOI: 10.1074/jbc.M102174200. View

11.

Alvarez Macedo M, Vazquez Antona C . Uncommon mitral valve anomalies associated with Ebstein anomaly. Rev Esp Cardiol (Engl Ed). 2021; 74(8):717-719. DOI: 10.1016/j.rec.2021.01.013. View

12.

Aluru J, Barsouk A, Saginala K, Rawla P, Barsouk A . Valvular Heart Disease Epidemiology. Med Sci (Basel). 2022; 10(2). PMC: 9228968. DOI: 10.3390/medsci10020032. View

13.

LeMaire S, McDonald M, Guo D, Russell L, Miller 3rd C, Johnson R . Genome-wide association study identifies a susceptibility locus for thoracic aortic aneurysms and aortic dissections spanning FBN1 at 15q21.1. Nat Genet. 2011; 43(10):996-1000. PMC: 3244938. DOI: 10.1038/ng.934. View

14.

Tajima K, Honda K, Yuzaki M, Kunimoto H, Okada Y, Nishimura Y . Congenital mitral regurgitation with Down syndrome. Asian Cardiovasc Thorac Ann. 2018; 26(2):139-141. DOI: 10.1177/0218492318755584. View

15.

Foffa I, Murzi M, Mariani M, Mazzone A, Glauber M, Ait Ali L . Angiotensin-converting enzyme insertion/deletion polymorphism is a risk factor for thoracic aortic aneurysm in patients with bicuspid or tricuspid aortic valves. J Thorac Cardiovasc Surg. 2012; 144(2):390-5. DOI: 10.1016/j.jtcvs.2011.12.038. View

16.

Fathallah M, Krasuski R . Pulmonic Valve Disease: Review of Pathology and Current Treatment Options. Curr Cardiol Rep. 2017; 19(11):108. DOI: 10.1007/s11886-017-0922-2. View

17.

Fishbein G, Fishbein M . Pathology of the Aortic Valve: Aortic Valve Stenosis/Aortic Regurgitation. Curr Cardiol Rep. 2019; 21(8):81. DOI: 10.1007/s11886-019-1162-4. View

18.

Balzer D . Pulmonary Valve Replacement for Tetralogy of Fallot. Methodist Debakey Cardiovasc J. 2019; 15(2):122-132. PMC: 6668735. DOI: 10.14797/mdcj-15-2-122. View

19.

Klaskova E, Zapletalova J, Kapralova S, Snajderova M, Lebl J, Tudos Z . Increased prevalence of bicuspid aortic valve in Turner syndrome links with karyotype: the crucial importance of detailed cardiovascular screening. J Pediatr Endocrinol Metab. 2017; 30(3):319-325. DOI: 10.1515/jpem-2016-0301. View

20.

Musfee F, Guo D, Pinard A, Hostetler E, Blue E, Nickerson D . Rare deleterious variants of NOTCH1, GATA4, SMAD6, and ROBO4 are enriched in BAV with early onset complications but not in BAV with heritable thoracic aortic disease. Mol Genet Genomic Med. 2020; 8(10):e1406. PMC: 7549564. DOI: 10.1002/mgg3.1406. View