Causes of Mitral Valve Prolapse
Myxomatous degeneration is the most common cause of mitral valve prolapse in the United States and Europe, representing a primary degenerative condition with genetic etiology. 1
Primary Causes
Myxomatous Degeneration (Most Common)
Myxomatous degeneration is the predominant etiology of MVP in developed countries, characterized by excess myxoid tissue accumulation, disruption of the normal three-layered leaflet architecture, leaflet thickening (≥5 mm defines "classic" MVP), and chordal elongation 1, 2
This condition exhibits autosomal dominant inheritance with incomplete penetrance and age- and sex-dependent expression, though the genetic basis is complex and heterogeneous involving multiple genes and chromosomes 1, 2
Genetic loci identified include chromosome 16p11.2-p12.1 (proven for bileaflet prolapse) and chromosome 13q31.3-q32.1 (associated with both bileaflet and posterior leaflet prolapse) 2
The molecular pathology involves a connective tissue disorder with altered extracellular matrix, mediated by matrix metalloproteinases, cysteine endoproteases, and tenomodulin 1
Myxomatous MVP is the most common cause of mitral regurgitation requiring surgical treatment in developed nations 1
Familial/Genetic Forms
Familial clustering occurs in approximately 16% of cases (4 of 25 pedigrees in one study), with clear autosomal dominant transmission patterns 2
First-degree relatives of patients with Morbus Barlow (severe bileaflet myxomatous prolapse) should undergo echocardiographic screening due to high heritability 2
Secondary Causes
Post-Inflammatory Changes
Post-inflammatory valve prolapse (PIVP) accounts for a substantial proportion of MVP cases (52% in one surgical series: 22 of 42 cases), characterized by fibrosis with vascularization and scattered inflammatory cell infiltration 3
Rheumatic fever is a documented cause of PIVP, with 7 of 22 patients in one series having a history of rheumatic fever 3
Post-inflammatory changes can occur with or without ongoing chronic inflammation and may coexist with myxomatous degeneration in the same valve 3
Rheumatic Heart Disease
In rheumatic MR, excessive leaflet tip motion (the surgical definition of prolapse) results from elongation or rupture of primary chords, together with annular dilatation, particularly in young patients with acute rheumatic carditis 4
This mechanism is most common in patients under 35 years with pure mitral regurgitation and becomes less common after the third decade when mitral stenosis predominates 4
Important distinction: The echocardiographic appearance in rheumatic disease differs from classic degenerative MVP—rheumatic valves show excessive tip motion without the characteristic billowing of leaflet bodies seen in myxomatous disease 4
Connective Tissue Disorders
Severe connective tissue disorders (e.g., Marfan syndrome, Ehlers-Danlos syndrome) can cause chordal rupture and MVP, though this is rare in children and represents only isolated case reports 4
These disorders affect the structural integrity of valve components through systemic collagen abnormalities 4
Ischemic/Functional Causes
Ischemic cardiomyopathy can lead to secondary MVP through papillary muscle dysfunction, fibrosis, or elongation 4
Hypertrophic obstructive cardiomyopathy represents another potential secondary etiology 4
Age-Related Patterns
Pediatric Population
In children, chordal rupture (causing excessive leaflet motion/prolapse) occurs predominantly in rheumatic carditis (7-17% of patients undergoing rheumatic MV repair) 4
Myxomatous degeneration and severe connective tissue disorders are extremely rare causes in the pediatric age group 4
Adult Population
In adults, the hierarchy shifts: myxomatous degeneration is the most common cause of chordal rupture, followed by endocarditis, then rheumatic heart disease 4
MVP is a degenerative condition that becomes more common with advancing age, with prevalence estimates of 1.3-2.4% in unselected populations using modern echocardiographic criteria 4, 5
Clinical Pearls
Prevalence has decreased from earlier estimates due to refined echocardiographic criteria; older studies using non-specific criteria overestimated prevalence 4
The diagnosis of prolapse should be made in parasternal long-axis view on echocardiography, not apical four-chamber view, to avoid false positives from the saddle-shaped annulus 4
Cumulative complication risk by age 75 is 5-10% for men and 2-5% for women, with complications including progressive mitral regurgitation, endocarditis, and sudden cardiac death 6
Patients with neither a murmur nor Doppler evidence of mitral regurgitation have a benign prognosis and can be reassured 6