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Genetics of bicuspid aortic valve: ready for clinical use?
  1. Jose F Rodriguez-Palomares1,2
  1. 1Department of Cardiology, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain
  2. 2Centro de Investigación Biomédica en Red-CV, CIBER CV, Madrid, Spain
  1. Correspondence to Dr Jose F Rodriguez-Palomares, Cardiology, Hospital Vall Hebrón, Barcelona 08035, Spain; jfrodriguezpalomares{at}

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Several mechanisms have been described to explain the aetiology of bicuspid aortic valve disease (BAV). On the one hand, haemodynamic factors by which an altered flow through the valve induces an abnormal cusp formation, and on the other, genetic factors given the presence of familial cases (6.4% of first-degree relatives)1 and its association with other left ventricular outflow tract (LVOT) abnormalities.

Although most BAV cases are sporadic, an autosomal dominant pattern of inheritance with an incomplete penetrance has been proposed with an estimated heritability between 47% and 89%.1 It is more prevalent in men (9.2% vs 3.5%, respectively), which suggests that the loss of genes on the X chromosome may predispose its condition, however, these genes have not been yet identified.

NOTCH1 has become the first gene associated with both familial2 and sporadic3 BAV and associated with other left-sided and right-sided congenital heart defects (such as tetralogy of Fallot, truncus arteriosus or hypoplastic left heart syndrome (HLHS)). This gene is highly expressed in the LVOT mesenchyme and endocardium at the location of the nascent valve cusps and the presence of haploinsufficiency has been associated with BAV and thoracic aortic aneurysms (TAA). Due to the common embryologic origin of the aortic valve, LVOT and proximal aorta, BAV frequently co-exists with other left-sided congenital heart lesions, such as coarctation (CoA), Shone complex and HLHS. It has been reported that 50%–85% of patients with CoA-associated BAV. The highest penetrance of BAV in a genetic syndrome occurs in women with Turner syndrome, which is caused by a partial or complete absence of one X chromosome. BAV appears in >30% of patients, and the prevalence of associated CoA, aortic aneurysms and acute aortic dissections exceeds that in sporadic BAV cases. However, NOTCH1 variants explain only a small proportion of familial (2%) …

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  • Contributors JFR-P is the sole contributor.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; externally peer reviewed.

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