The aortic valve regulates blood flow from the heart’s main pumping chamber, the left ventricle, into the body’s largest artery, the aorta. When this valve develops abnormally before birth, it results in Bicuspid Aortic Valve (BAV). BAV is the most common congenital heart defect, affecting a significant portion of the population. Extensive research confirms that BAV frequently has a strong hereditary basis. This inherited component drives clinical recommendations for screening and monitoring affected individuals and their families.
Defining the Condition
The healthy aortic valve, known as a trileaflet valve, has three small, equal-sized flaps of tissue (leaflets or cusps) that ensure one-way blood flow. In contrast, a Bicuspid Aortic Valve develops with only two functional leaflets, often unequal in size and shape, resulting from two cusps fusing together during fetal development. This structural malformation occurs in an estimated 1% to 2% of the general population, making it a frequent congenital abnormality. The valve must open fully when the heart contracts and close tightly to prevent blood from leaking back. While this two-leaflet structure can function adequately for many years, its abnormal design creates mechanical stress over time.
The Genetic Basis
Bicuspid Aortic Valve is strongly heritable, meaning it clusters within families, with heritability estimates ranging as high as 90%. The inheritance pattern is typically described as Autosomal Dominant, where only one copy of the affected gene is needed to potentially pass the trait down to a child. The expression of the gene is characterized by incomplete or variable penetrance, meaning that not every person who inherits the genetic predisposition will actually develop the BAV defect. This complexity suggests that other genetic or environmental factors must contribute to the final expression of the condition. Approximately 7.3% of screened first-degree relatives of an affected individual are found to also have BAV, a prevalence significantly higher than that of the general population.
Researchers have identified several genes involved in valve formation (valvulogenesis) during the first eight weeks of gestation. One of the most studied genes is NOTCH1, which codes for a receptor protein important for cell-to-cell signaling in development. However, known pathogenic variants in NOTCH1 account for only about 2% of familial BAV cases, indicating the involvement of a complex network of multiple genes. The shared genetic link between the valve and the aorta itself is a key area of study, as both structures arise from related embryonic tissue.
Associated Health Risks
The abnormal valve structure often fails to function smoothly over a lifetime, leading to significant complications. The two leaflets create turbulent blood flow, which causes increased wear and tear on the valve tissue. This mechanical stress can lead to progressive hardening and narrowing of the valve opening, known as Aortic Stenosis. Stenosis forces the left ventricle to pump harder to push blood through the restricted opening, which can cause the heart muscle to thicken over time.
Alternatively, the irregular leaflets may not close completely, allowing blood to leak backward into the heart, a condition called Aortic Regurgitation or insufficiency. Both stenosis and regurgitation can eventually lead to symptoms like shortness of breath, fatigue, or chest pain.
Beyond the valve itself, BAV is frequently associated with an abnormality of the aorta wall, known as aortopathy. This involves the progressive dilation and weakening of the ascending aorta, which can occur independently of the severity of the valve dysfunction. The dilation can lead to a thoracic aortic aneurysm and carries an increased risk of an aortic dissection. Patients with BAV also face a higher lifetime risk of infective endocarditis, a severe bacterial infection of the heart valve lining.
Diagnosis and Family Screening
Because BAV often causes no symptoms for many years, the condition is commonly diagnosed incidentally during tests performed for other reasons. The standard diagnostic method is an Echocardiogram, an ultrasound of the heart that allows physicians to visualize the valve’s structure and function. This imaging confirms the presence of the two-leaflet structure and assesses the degree of any stenosis or regurgitation.
Given the strong hereditary nature of the condition, international guidelines recommend screening all first-degree relatives (parents, siblings, and children) of an affected individual. This screening is typically performed using a simple echocardiogram to detect BAV and any associated aortic dilation early. Early detection allows for the implementation of a surveillance program, including periodic echocardiograms, to monitor the valve and aorta for changes.
The goal of this surveillance is to identify complications before they become severe, enabling timely intervention. While there is no treatment to reverse the BAV, surgery, such as valve replacement or repair, is performed if complications like severe stenosis or significant aortic dilation develop. Recognizing the familial risk allows for preventative monitoring and management.