X-linked myxomatous valvular disease is characterized by mitral valve dystrophy frequently associated with degeneration of the aortic valves affecting males and, to a lower severity, females. The first localization of a gene for myxomatous valvular diseases is the first step for the subclassification of these diseases. Abbreviations and Acronyms AML = anterior mitral leaflet F.VIII = antihemophilic factor VIII LAA = left atrial area LVOTD = left ventricular outflow tract diameter MVD = myxomatous valve dystrophies PML = posterior mitral leaflet RJA = regurgitating jet area Valvular disease with myxomatous degeneration forms a complex group of disorders. Common histological features and a clinical continuum from isolated nonsyndromic valvular defects (e.g., idiopathic mitral valve prolapse) to multivalvular diseases and syndromic disorders (e.g., Marfan syndrome) make it difficult to subclassify these heterogeneous and complex pathologies. Defects in fibrillin (1) and collagen genes (2) have already been identified in syndromic valvular disease. In other valvular dystrophies with myxomatous degeneration, identification of genetic defects would appear to be an essential step in their subclassification
In nonsyndromic valvular dystrophies with myxomatous degeneration, idiopathic mitral valve prolapse is by far the most common defect, occurring in 2% to 4% of the population (3) and displaying a broad clinical spectrum from mild valve defects without clinical repercussions to severe valvular disease (4). The valve anomaly is the main defect, but some studies are in favor of a more diffuse disease affecting other cardiac structures (5). Although the exact prevalence of inherited cases is still uncertain, most familial forms appear to be inherited in an autosomal dominant manner with incomplete penetrance (6). There is also clinical evidence of genetic heterogeneity (7). Despite autosomal transmission, the disease is twice as frequent in females as in males (8), but more severe in the latter (9). A second type of inherited nonsyndromic valvular dystrophy was identified three decades ago by Monteleone and Fagan (10). This apparently rare disease, known as sex-linked valvular dysplasia, is supposedly transmitted as an X-linked recessive trait and may involve one or several valves in affected males. Both forms display classical histological abnormalities of myxomatous valve degeneration, with fragmentation of collagenous bundles within the valve fibrosa and accumulation of proteoglycan.