Journal of Cardiovascular Translational Research

, Volume 4, Issue 6, pp 741-747

First online:

Mitral Valve Disease in Marfan Syndrome and Related Disorders

  • Daniel P. JudgeAffiliated withDivision of Cardiology, Johns Hopkins UniversityUniversité Paris-Descartes, Sorbonne Paris Cité Email author 
  • , Rosanne RoufAffiliated withDivision of Cardiology, Johns Hopkins University
  • , Jennifer HabashiAffiliated withDivision of Pediatric Cardiology, Johns Hopkins UniversityMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University
  • , Harry C. DietzAffiliated withMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins UniversityHoward Hughes Medical Institute

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Marfan syndrome (MFS) is a systemic disorder of the connective tissue with pleiotropic manifestations due to heterozygous FBN1 mutations and consequent upregulation of TGFβ signaling in affected tissues. Myxomatous thickening and elongation of the mitral valve (MV) leaflets commonly occur in this condition. Investigation of murine models of this disease has led to improved understanding of the mechanisms that underlie many of the phenotypic features of MFS, including MV disease. Loeys–Dietz syndrome (LDS) is a related disorder due to heterozygous mutations in the genes encoding subunits of the TGFβ receptor, and it may also involve the MV leaflets with similar elongation and thickening of the MV leaflets. Although the genetic basis and pathogenesis of nonsyndromic MV prolapse has been elusive to date, insights derived from monogenic disorders like MFS and LDS can be informative with regard to novel gene discovery and investigation into the pathogenesis of MV disease. This manuscript will review the prevalence of MV disease in MFS, its pathogenic basis as determined in mice with Fbn1 mutations, and ongoing studies that seek to better understand MV disease in the context of fibrillin-1 deficiency or excessive TGFβ signaling.


Mitral valve Marfan TGF-beta