The aortic valve regulates the flow of oxygen-rich blood from the heart’s left ventricle into the aorta, the body’s largest artery. This valve typically consists of three tissue flaps, known as leaflets or cusps, which open and close with each heartbeat to ensure blood moves in one direction. A bicuspid aortic valve (BAV) is a common congenital heart condition where this valve forms with only two leaflets instead of the usual three. This structural difference raises questions about its underlying causes, particularly regarding a potential genetic origin.
Understanding a Bicuspid Aortic Valve
Normally, the aortic valve is tricuspid, having three leaflets that open widely to allow blood flow and close securely to prevent backflow. In contrast, a bicuspid aortic valve has only two leaflets, which can sometimes be thicker or stiffer than normal. This altered structure can impact how effectively the valve functions over time.
The two leaflets in a bicuspid valve may not open or close as efficiently as three, potentially leading to complications such as narrowing of the valve opening, known as aortic stenosis, or a leaky valve, termed aortic regurgitation. Both conditions force the heart to work harder, which can strain the heart muscle over many years. BAV is the most common congenital heart defect, affecting 1% to 2% of the general population.
The Genetic Link to BAV
Bicuspid aortic valve is a heritable condition with a significant genetic component. Research indicates that BAV frequently runs in families, suggesting a strong genetic influence. Despite its hereditary nature, BAV can also occur sporadically, meaning without a known family history of the condition.
Current understanding points to a complex genetic architecture rather than a single gene mutation being solely responsible for BAV. Studies have identified several genes and chromosomal regions associated with BAV development. For instance, mutations in genes like NOTCH1 and GATA5 have been linked to human BAV, though these account for a relatively small percentage of cases. Other genes, including ACTA2, SMAD3, TGFBR1, TGFBR2, TGFB2, TGFB3, MYH11, MAT2A, and LOX, have also been implicated, often in conjunction with associated conditions like thoracic aortic aneurysms. The high heritability of BAV, estimated at up to 89%, indicates genetic factors play a substantial role in its development.
Inheritance and Family Risk
The inheritance pattern of bicuspid aortic valve often follows an autosomal dominant model, characterized by incomplete penetrance and variable expressivity. Autosomal dominant inheritance means that only one copy of an altered gene is sufficient for an individual to inherit the predisposition for the condition. However, “incomplete penetrance” signifies that not everyone who inherits the genetic predisposition will develop BAV, or they may have a milder form that goes undiagnosed.
“Variable expressivity” further explains why individuals within the same family who inherit the condition may experience different degrees of severity or associated complications. This means one family member might have a well-functioning bicuspid valve with no symptoms, while another could develop severe stenosis or regurgitation. Given this inheritance pattern, first-degree relatives (parents, siblings, and children) of an individual with BAV have an increased risk of also having the condition. The prevalence of BAV among first-degree relatives can be up to 9%, or 24% in families with multiple affected members, a tenfold increase compared to the general population.
Associated Conditions and Family Screening
Individuals with a bicuspid aortic valve often experience other cardiovascular conditions that can have a genetic basis or arise as a consequence of the valve’s altered structure. These commonly include aortic root dilation (widening of the aorta) and thoracic aortic aneurysms (bulges that can lead to life-threatening dissections or ruptures). Coarctation of the aorta, a narrowing of the large artery carrying blood from the heart to the body, is another frequently associated congenital defect.
Understanding these associations is important because they can have familial tendencies and require ongoing medical monitoring. Due to the heritable nature of BAV, screening for the condition in family members is often recommended. This typically involves echocardiography, a non-invasive ultrasound of the heart, for first-degree relatives to assess valve structure and aortic dimensions. Genetic counseling is a valuable resource, providing families with a comprehensive assessment of individual and familial risk and helping them understand the implications of BAV and its associated conditions.