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Genetics of syndromic and non-syndromic mitral valve prolapse
  1. Thierry Le Tourneau1,2,
  2. Jean Mérot1,
  3. Antoine Rimbert1,
  4. Solena Le Scouarnec1,
  5. Vincent Probst1,2,
  6. Hervé Le Marec1,2,
  7. Robert A Levine3,
  8. Jean-Jacques Schott1,2
  1. 1 l’institut du thorax, INSERM, CNRS, Université de Nantes, Nantes, France
  2. 2 l’institut du thorax, CHU de Nantes, Nantes, France
  3. 3 Cardiac Ultrasound Laboratory, Harvard Medical School, Massachusetts General Hospital, Boston, Massachusetts, USA
  1. Correspondence to Professor Thierry Le Tourneau, Laboratoire d’Explorations Fonctionnelles, Hotel Dieu, Nantes Cedex 44093, France; thletourneau{at}


Mitral valve prolapse (MVP) is a common condition that affects 2%–3% of the general population. MVP is thought to include syndromic forms such as Marfan syndrome and non-syndromic MVP, which is the most frequent form. Myxomatous degeneration and fibroelastic deficiency (FED) are regarded as two different forms of non-syndromic MVP. While FED is still considered a degenerative disease associated with ageing, frequent familial clustering has been demonstrated for myxomatous MVP. Familial and genetic studies led to the recognition of reduced penetrance and large phenotypic variability, and to the identification of prodromal or atypical forms as a part of the complex spectrum of the disease. Whereas autosomal dominant mode is the common inheritance pattern, an X linked form of non-syndromic MVP was recognised initially, related to Filamin-A gene, encoding for a cytoskeleton protein involved in mechanotransduction. This identification allowed a comprehensive description of a new subtype of MVP with a unique association of leaflet prolapse and paradoxical restricted motion in diastole. In autosomal dominant forms, three loci have been mapped to chromosomes 16p11-p12, 11p15.4 and 13q31-32. Although deciphering the underlying genetic defects is still a work in progress, DCHS1 mutations have been identified (11p15.4) in typical myxomatous disease, highlighting new molecular pathways and pathophysiological mechanisms leading to the development of MVP. Finally, a large international genome-wide association study demonstrated the implication of frequent variants in MVP development and opened new directions for future research. Hence, this review focuses on phenotypic, genetic and pathophysiological aspects of MVP.

  • mitral valve prolapse
  • myxomatous disease
  • genetic
  • Filamin-A
  • Dachsous
  • animal model

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  • Contributors TLT planned, wrote and submitted the manuscript. JM, AR, SLS, VP, HLM and JJS wrote a part and reviewed the manuscript. RAL reviewed and amended the manuscript.

  • Funding Leducq Foundation Transatlantic Network of Excellence in Mitral Valve Disease (2008–2013, Paris, France); Fondation GenaVie (TLT, 2010, Nantes, France); Fédération Française de Cardiologie (TLT, 2011 and 2014, Paris, France); Fondation Coeur & Recherche (TLT, 2013, Paris, France); French Ministry of Health ‘PHRC National 2007’ (VP, HLM, no 20 17); and ‘PHRC I 2012’ (TLT, API12/N/019, Paris, France). NIH (RAL): HL109506, HL128099 and R01 HL141917. Ellison Foundation (RAL, Boston, MA). Inserm Translational Research Grant (2012–2016, Paris, France) to TLT.

  • Competing interests None declared.

  • Provenance and peer review Commissioned; externally peer reviewed.