Is Bicuspid Aortic Valve Morphology Genetically Determined? A Family-Based Study

Area of Science:

• Cardiology
• Genetics
• Congenital Heart Disease

Background:

• Bicuspid aortic valve (BAV) is a prevalent congenital heart defect with increased familial occurrence.
• BAV exhibits diverse phenotypes (cusp fusion morphologies) linked to varied clinical courses and prognoses.
• The genetic determinants of BAV morphology remain largely unknown.

Purpose of the Study:

• To investigate the role of genetics in determining bicuspid aortic valve (BAV) morphology using familial cohorts.
• To assess the concordance of BAV phenotypes among first-degree relatives.
• To compare observed morphologic concordance with chance expectations.

Main Methods:

• Echocardiographic evaluation of patients with BAV and their first-degree relatives.
• Calculation of BAV phenotype concordance in familial pairs.
• Systematic literature review to augment cohort data and calculate overall concordance rates.

Main Results:

• BAV was diagnosed in 14% of screened relatives across 31 families.
• Morphologic classification included Type 0 (12.3%), Type 1-LR (66.2%), Type 1-RN (15.4%), Type 1-NL (4.6%), and Type 2 (1.5%).
• Morphologic concordance among 120 first-degree relative pairs was 62%, not significantly higher than expected by chance.

Conclusions:

• Intrafamilial variability in BAV morphology suggests non-Mendelian genetic influences.
• BAV phenotype is likely determined by factors beyond simple genetic inheritance.
• Differential prognoses associated with BAV morphologies imply potential variability in clinical outcomes even among relatives.