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CLINICAL STUDIES

Clinical characteristics of a familial inherited myxomatous valvular dystrophy mapped to Xq28

Jean-Noël Trochu, MD^*, Florence Kyndt, PhD, Jean-Jacques Schott, PhD, Jean-Pierre Gueffet, MD^*, Vincent Probst, MD^*, Bernard Bénichou, MD, PhD and Hervé Le Marec, MD, PhD^*

^* Clinique Cardiologique et des Maladies Vasculaires, Hôpital G&R Laennec, CHU de Nantes, Nantes, France
Laboratoire de Physiopathologie et Pharmacologie Cellulaire et Moléculaire, INSERM CJF 96-01, Nantes, France
Service de Génétique Médicale CHU de Nantes, Nantes, France

Manuscript received January 12, 1999; revised manuscript received December 10, 1999, accepted February 3, 2000.

Reprint requests and correspondence: Dr. Hervé Le Marec, Clinique Cardiologique et des Maladies Vasculaires, CHU de Nantes, 44093 Nantes cedex, France
herve.lemarec{at}chu-nantes.fr

OBJECTIVES

The purpose of this study was to describe the phenotypic characteristics of an inherited myxomatous valvular dystrophy mapped to Xq28.

BACKGROUND

Myxomatous valve dystrophies are a frequent cause of valvular diseases, the most common being idiopathic mitral valve prolapse. They form a group of heterogeneous diseases difficult to subclassify. The first mapping of the gene for a myxoid valvular dystrophy to Xq28 allowed investigation of the phenotype of affected members in a large family and characterization of the disease.

METHODS

Among the 318 members in the pedigree, 89 agreed to participate in this study. Phenotypic characteristics were investigated using clinical examination, transthoracic echocardiography and biological analysis (F.VIII activity). Genetic status was based on haplotype analysis.

RESULTS

Among 46 males, 9 were hemizygous to the mutant allele and had an obvious mitral and/or aortic myxomatous valve defect, and 4 had undergone valvular surgery. All had typical mitral valve prolapse associated in six cases with moderate to severe aortic regurgitation. The valve defect cosegregated with mild hemophilia A (F.VIII activity = 0.32 ± 0.05). The 37 remaining males had normal valves and normal F.VIII activity. Heterozygous women were identified on the basis of their haplotypes. Among the 17 women heterozygous to the mutant allele, moderate mitral regurgitation was present in 8, associated with mild mitral valve prolapse in 1 and aortic regurgitation in 3, whereas 2 women had isolated mild aortic regurgitant murmur. In heterozygotes, the penetrance value was 0.60 but increased with age.

CONCLUSION

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

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