Mitral valve prolapse (MVP) is a common heart condition affecting approximately 2% to 3% of the general population. It is characterized by a structural change in one of the heart’s four valves. While many cases are mild and require no intervention, the condition frequently runs in families, suggesting a strong heritable component.
What Mitral Valve Prolapse Is
The mitral valve is located between the heart’s upper left chamber (left atrium) and the lower left chamber (left ventricle). Its purpose is to ensure that oxygenated blood flows in one direction, opening to allow blood into the ventricle and closing tightly to prevent backflow when the ventricle contracts.
Mitral valve prolapse occurs when one or both of the valve’s flaps, called leaflets, become abnormally stretchy, thickened, or elongated. This structural change, often called myxomatous degeneration, causes the leaflets to bulge backward, or prolapse, into the left atrium during contraction.
If the valve does not close tightly due to the prolapse, blood can leak backward into the atrium, a condition known as mitral regurgitation. The severity of this backflow determines the clinical impact of MVP. Most cases are benign, but severe regurgitation can strain the heart and lead to complications.
Evidence for a Genetic Connection
The familial nature of mitral valve prolapse has been recognized for decades through observational studies. Research indicates that a significant portion of MVP cases, estimated to be between 35% and 50%, show a familial pattern, suggesting a clear inherited risk.
For first-degree relatives of an affected individual, the prevalence of MVP can be as high as 30%, substantially greater than the general population risk. This strong clustering points to a high degree of heritability, estimated to exceed 60% for the condition.
The specific pathology of myxomatous degeneration, involving abnormal connective tissue within the valve leaflets, is often found to be familial. This provided the impetus for researchers to search for specific genetic mutations responsible for the condition.
Patterns of Inheritance
Autosomal Dominant Inheritance
For many families, MVP follows an autosomal dominant inheritance pattern. This means a person only needs to inherit one copy of the altered gene from either parent to have a predisposition to the condition. This inheritance is often characterized by incomplete penetrance, meaning not everyone who inherits the gene alteration will develop the physical signs of MVP.
Non-Syndromic MVP
The specific genes responsible for non-syndromic, isolated MVP—the most common form—are still being mapped, but several have been identified. Mutations in the DCHS1 and DZIP1 genes, for instance, have been linked to myxomatous forms of MVP in some families. The products of these genes play a role in maintaining the structural integrity of the valve tissue.
Syndromic and X-Linked Forms
A less common but more severe form of MVP has been linked to X-linked inheritance, associated with mutations in the FLNA (Filamin A) gene. Because this gene is on the X chromosome, the condition tends to be more severe in males who inherit the mutation compared to females.
MVP frequently appears as a feature of known connective tissue disorders, such as Marfan syndrome and Ehlers-Danlos syndrome. These syndromic forms are caused by mutations in genes like FBN1, leading to connective tissue weakness throughout the body.
Polygenic Nature
MVP is often a polygenic or multifactorial condition, meaning it does not always result from a single, simple mutation. Many cases likely involve the combined effects of multiple common gene variants, each contributing a small amount of risk, alongside various environmental factors. This complex genetic architecture explains why the condition can manifest with varied severity and presentation, even among members of the same family.
Other Causes of MVP
Not all instances of mitral valve prolapse are inherited. Many cases are considered sporadic or idiopathic, meaning the cause is unknown and the condition appears without a clear family history.
MVP can also be acquired as a consequence of other underlying health issues. Prior infectious diseases, such as rheumatic fever, can cause inflammation and scarring of the heart valves, leading to structural abnormalities.
Other acquired causes include structural changes in the chest wall, such as scoliosis, which can alter the mechanical forces on the heart. These secondary causes demonstrate that MVP is influenced by a combination of inherent biological factors and external events.