In severe cases of classic MVP, complications include mitral regurgitation, infective endocarditis, congestive heart failure, and, in rare circumstances, cardiac arrest.

[7] Although mid-systolic click (the sound produced by the prolapsing mitral leaflet) and systolic murmur associated with MVP were observed as early as 1887 by physicians M. Cuffer and M. Barbillon using a stethoscope.

[2][8][9] Upon auscultation of an individual with mitral valve prolapse, a mid-systolic click, followed by a late systolic murmur heard best at the apex, is common.

[12] Historically, the term mitral valve prolapse syndrome has been applied to MVP associated with palpitations, atypical precordial pain, dyspnea on exertion, low body mass index, and electrocardiogram abnormalities (ventricular tachycardia), syncope, low blood pressure, headaches, lightheadedness, exercise intolerance, gastrointestinal disturbances, cold extremities and other signs suggestive of autonomic nervous system dysfunction (dysautonomia).

[11] The severity of regurgitation in MVP is typically estimated using a grading system:[16][17][18] People with mitral valve prolapse might have arrhythmic mitral valve prolapse which includes higher incidence of ventricular contraction disorders and tachycardia compared to the normal population, although the relationship between both phenomena is not entirely clear.

[32] The recurrence of rheumatic fever is relatively common in the absence of maintenance of low dose antibiotics, especially during the first three to five years after the first episode.

Rheumatic fever, since the advent of routine penicillin administration for Strep throat, has become less common in developed countries.

Patients with classic mitral valve prolapse have excess connective tissue that thickens the spongiosa and separates collagen bundles in the fibrosa.

[29] Common risk factors in diagnostics for severe, arrhythmic mitral valve prolapse include: MVP is understood histologically, as a form of myxomatous degeneration, which is a type of connective tissue changes.

This proliferation is associated with the accumulation of deposits of mucopolysaccharide, which have a high water content, which leads to an increase in the thickness and redundancy (excess tissue) of the leaflets of the mitral valve.

[43] Also in people with MVP, there is an increase in the content of type III collagen, a protein that provides structure and strength to tissues.

[43][44] Mitral valve prolapse is a genetically heterogeneous autosomal dominant trait, which can be passed down from one parent to child, who will have a 50% chance to inherit the mutated gene.

It was found that primary cilia loss during development results in progressive myxomatous degeneration and profound mitral valve pathology.

[23] To date, only one of the genes that have been associated with MVP is a direct regulator of connective tissue maintenance and extracellular matrix composition: TLL1, in a gain-of-function mechanism.

This upregulation is associated with increased serotonin (5HT) receptor signaling which is involved in the remodeling of the mitral valve prolapse.

The researchers also found that blocking 5HTR2B can reduce mitral valve interstitial cells (MVIC) activation in vitro and MV remodeling in vivo.

Findings suggest that SSRIs may accelerate degenerative mitral valve regurgitation (DMR), particularly in people with a specific 5-HTTLPR genotype ('long-long').

[29] Classical prolapse may be subdivided into symmetric and asymmetric, referring to the point at which leaflet tips join the mitral annulus.

Patients with asymmetric prolapse are susceptible to severe deterioration of the mitral valve, with the possible rupture of the chordae tendineae and the development of a flail leaflet.

Flail prolapse occurs when a leaflet tip turns outward, becoming concave toward the left atrium, causing the deterioration of the mitral valve.

[58] Those with mitral valve prolapse and symptoms of dysautonomia (palpitations, chest pain) may benefit from beta-blockers (e.g., propranolol, metoprolol, bisoprolol).

Current ACC/AHA guidelines promote repair of mitral valve in people before symptoms of heart failure develop.

Thereafter, they concluded that "prophylaxis for dental procedures should be recommended only for patients with underlying cardiac conditions associated with the highest risk of adverse outcome from infective endocarditis.

These include the HACEK organisms, which are part of the normal oropharyngeal flora and are responsible for perhaps 5 to 10% of infective endocarditis affecting native valves.

The worsening of the disorder can be delayed by avoiding smoking, the use of contraceptives (because they have the risk of clotting) and regulating the amount and type of exercise and nutrition under the supervision of a health professional.

[62] In a Taiwanese CHIEF heart study of Asian adult military personnel, it was estimated that out of 2442 people in Hualien aged 18 to 39, mitral valve prolapse occurred in 3.36%.

[3] In a human and mice study of MVP, a relationship was found between MVP and progressive fibrosis effects on left ventricular structure, which suggests the cause of molecular and cellular changes are a response of papillary and inferobasal myocardium to increased chordal tension from prolapsing mitral valve leaflets.

[69] In 2019 an experimental adeno-associated virus (AAV)-based gene therapy method was developed by Rejuvenate Bio, a biotechnology company.