Mitral valve prolapse [89 genes]

Mitral valve prolapse (MVP) is classically defined as a displacement or protrusion of mitral leaflets above the mitral annulus and towards the atrium, determining their hypermobility. This alteration may be benign, but it can also be associated with complications due to progressing mitral valve insufficiency, chordal rupture, or endocarditis. The most severe form is associated with mitral annular disjunction. Some forms of MVP associated with complex ventricular arrhythmias have also been described, for which different pathophysiological mechanisms have been proposed (PMID: 24867995).

MVP can be one of many manifestations identified in some syndromic disorders (such as Marfan syndrome) or can constitute the single or predominant cardiovascular manifestation (non-syndromic MVP), which is the most common form. Within the latter, myxomatous mitral valve degeneration and fibroelastic deficiency are worth highlighting. Non-syndromic MVP can show variable percentages of familiar aggregation, which is significantly higher in myxomatous degeneration (PMID: 28993406).

The indication and ultimate clinical usefulness of genetic testing for MVP has not been established by clinical practice guidelines, which emphasize the importance of increasing evidence supporting the role of genetics on the pathophysiology, patient and family management, and risk of progression of this disease (PMID: 34453165). MVP could be the first or the most florid manifestation in the context of a syndromic entity in which genetics could play a key role by providing an etiological diagnosis, thereby dramatically changing the course of future patient management, including the need to screen for the involvement of other organs or symptoms. Genetic testing for non-syndromic MVP could provide relevant information, as the presence of an actionable variant could be useful for cascade family screening.

Mitral valve prolapse (MVP) is a frequent entity, with an estimated prevalence between 2% and 3% of the global population, and it is recognized as one of the most common causes of heart valve surgery.

This panel is particularly indicated in cases of syndromic and non-syndromic MVP with an early onset (before age 60), familial aggregation, suspected de novo presentation, and/or structural alterations or congenital defects in large vessels.

The yield of genetic testing for MVP is highly dependent on the presence of manifestations suggestive of syndromic disease, familial aggregation, and/or involvement of other vascular structures. In non-syndromic forms, the yield of the genetic test is higher when there is underlying myxomatous mitral valve degeneration, while it is lower for those forms associated with fibroelastic deficiency (PMID: 29352010).

In this sense, this panel includes all the described genes with a demonstrated association with this entity, both those related to syndromic and to non-syndromic forms of the disease. Moreover, in the case of non-syndromic MVP, genes with initial clinical/functional evidence are included.