Abstract
BackgroundMyxomatous mitral valve prolapse is a common cardiac abnormality. Morbus Barlow is characterized by excess myxomatous leaflet tissue, bileaflet prolapse or billowing, chordae elongation and annular dilatation with or without calcification. Extensive myxoid degeneration with destruction of the normal three-layered leaflet tissue architecture is observed histologically in such patients. Autosomal dominant inheritance with an age and sex-dependent expression has long been recognised. This review explores the current understanding of the genetics of bileaflet prolapse, with a focus on genetic analysis and the role for echocardiographical screening of the first degree relatives of affected patients.MethodsSystematic literature searches were performed using PubMed and Embase up to September 2017. In Disse et al.’s study (study one) first degree relatives of 25 patients with Morbus Barlow who underwent mitral valve repair were screened for bileaflet valve prolapse. In Nesta et al.’s study one family with three living generations of 43 individuals with 9 confirmed cases of MVP was screened. Genotyping was performed in four families for 344 microsatellite markers from Chromosome 1 to 16.ResultsIn study one, autosomal dominant inheritance was shown in four pedigrees. Genome-wide linkage analysis of the most informative pedigree (24 individuals, three generations) showed a significant linkage for markers mapping to chromosome 16p. Linkage to this locus was confirmed in a second family within the same study, but was excluded in the remaining two pedigrees. In study two an autosomal dominant locus was mapped to chromosome 13. 8 of the 9 individuals affected were found to suffer from bileaflet prolapse.ConclusionsBarlow’s disease is a heritable trait but the genetic causes remain largely elusive. Ch16p11.2-p12.1 is the only locus proven to be associated with bileaflet prolapse. Locus 13.q31.3-q32.1 was shown to cause bileaflet as well as posterior leaflet prolapse. This review intends to make physicians aware of genetic causes of myxomatous mitral valve prolapse, thereby emphasising the importance of cardiological examination of first-degree relatives of patients with Morbus Barlow. Integrated and more comprehensive studies are needed for identification of genes involved in this heterogenic disease. Further genomic studies may facilitate more individualised and accurate risk assessment and may help to develop possible preventive stategies for patients in the future.
Highlights
Myxomatous mitral valve prolapse is a common cardiac abnormality
All relevant studies were included if published in a peerreviewed journal and if the following inclusion criteria were met (Fig. 1): a) Affected individuals were diagnosed with myxomatous mitral valve disease and diagnosis was confirmed by histological examination or patients were found to have bileaflet mitral valve prolapse by echocardiography b) The patients had a non-syndromic Mitral valve prolapse (MVP) c) Genetic analysis was performed
Individuals with histological proof of Myxomatous mitral valve disease (MMVD) who underwent mitral valve surgery and those with echocardiographic evidence of bileaflet prolapse were selected for subsequent genetic analysis, including their first-degree relatives
Summary
Morbus Barlow is characterized by excess myxomatous leaflet tissue, bileaflet prolapse or billowing, chordae elongation and annular dilatation with or without calcification. Myxomatous mitral valve disease (MMVD) is a common cardiac anomaly which affects up to 5% of the general population [1]. It is characterized by a wide spectrum of clinical and electrocardiographic features, ranging from no symptoms (in the vast majority of individuals) to symptomatic mitral regurgitation, endocarditis, cerebral embolism and arrhythmias [1]. Surgeons refer to Barlow’s disease in the presence of extensive myxoid degeneration, chordae elongation and annular dilatation with prolapse of one or both mitral valve leaflets. The molecular pathways leading to MMVD are yet to be clarified [2]
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