Mitral valve prolapse: a consistent manifestation of type IV Ehlers-Danlos syndrome. The pathogenetic role of the abnormal production of type III collagen.

Abstract

To evaluate whether abnormal production of type III collagen, the characteristic biochemical feature of patients with the type IV Ehlers-Danlos syndrome, consistently predisposes to mitral valve prolapse, we evaluated the family of a proband with classic type IV Ehlers-Danlos syndrome. Production of type III collagen was assessed with the use of cultured skin fibroblasts. Mitral valve prolapse was detected by M-mode and two-dimensional echocardiography. Biochemical abnormalities in the production of type III collagen and echocardiographic findings of mitral valve prolapse were completely concordant. All patients with abnormal production of type III collagen had mitral valve prolapse and all subjects with normal production of type III collagen had entirely normal echocardiograms. Six of the eight patients with abnormal production of type III collagen had subtle cutaneous abnormalities. The consistent association of abnormal production of type III collagen and mitral valve prolapse in this family suggests that this abnormality of collagen may give rise to mitral valve prolapse.

The Relationship Between Echocardiographic Features of Mitral Valve and Elastic Properties of Aortic Wall and Beighton Hypermobility Score in Patients With Mitral Valve Prolapse

“…33) In another study, the concordance between inadequate production of type III collagen and echocardiographic findings of MVP in patients with type IV Ehler-Danlos syndrome have suggested that this collagen abnormality may be the responsible factor in patients with this syndrome. 34) Abnormalities of collagen have been found in myxomatous or floppy valves of patients with MVP [11][12][13] that coincide with those identified in skin biopsies of patients with hypermobility syndrome 9) leading to the suggestion of a common pathogenetic mechanism of abnormal production or maturation of collagen. 14) Several clinical observations have led to the speculation that primary MVP syndrome represents a generalized disorder of connective tissue.…”

Extracellular Matrix Remodeling and Organization in Developing and Diseased Aortic Valves

“…29 -31 In addition, mitral valve prolapse and pulmonary valve stenosis have been linked to mutations in the collagen type 3 and tenascin X genes. 32,33 Therefore, a structural or functional defect in a single ECM protein is sufficient to cause valve disease, but the mechanisms by which ECM protein insufficiency or dysfunction lead to valve pathogenesis is not known. The disorganization of ECM structure in congenitally malformed valves may lead to abnormal signaling cascades, which in turn result in VIC dysregulation of ECM synthesis, consistent with the idea that valve disease has developmental origins.…”

Prevalence of Mitral Valve Prolapse in Saudi Sickle Cell Disease Patients in Dammam — A Prospective-Controlled Echocardiographic Study

“…17 There was also no significant difference in BSA of the two groups of patients studied by Lippman et al 11 The ease of diagnosis of MVP by echocardiography and the wave of interest that followed its initial description resulted in numerous case reports and small clinical studies claiming association of MVP with a wide variety of conditions. [6][7][8][9][10][11][12][13][14][15][16] A good example is Marfan syndrome, which has been variously reported to be associated with MVP. 6,7 This is a rare condition occurring in one per 10,000 population.…”

“…3 A wide range of conditions have been reported to be associated with MVP. [6][7][8][9][10][11][12][13][14][15][16] Many of these conditions are in themselves rare and the reports are based mostly on case reports and small clinical studies. 3 With an MVP prevalence of 2.5% to 5% in the general population, 3,17 many of these reported associations appear weak.…”