Genetics and pathophysiology of mitral valve prolapse

Area of Science:

• Cardiology
• Genetics
• Pathophysiology

Background:

• Mitral valve prolapse (MVP) affects 2-3% of the population, with advanced stages carrying a 10-15% annual complication rate.
• Complications include heart failure, atrial fibrillation, ventricular arrhythmia, and sudden cardiac death, highlighting the complexity and incomplete understanding of MVP.
• MVP can be syndromic or non-syndromic, with autosomal dominant inheritance being the primary mode, and can be classified into myxomatous degeneration, fibroelastic deficiency, and Filamin A-related MVP.

Purpose of the Study:

• To explore the genetic underpinnings of mitral valve prolapse (MVP).
• To review current understanding of MVP pathophysiology, including genetic defects and common variants.
• To discuss the role of animal models and genetic counseling in MVP research and management.

Main Methods:

• Review of genetic studies, including familial approaches and genome-wide association studies (GWAS).
• Analysis of identified causative genes (e.g., FLNA, DCHS1, DZIP1) in myxomatous MVP.
• Examination of animal models for MVP research and exploration of pathophysiological pathways.

Main Results:

• Specific genes (FLNA, DCHS1, DZIP1) are implicated in familial myxomatous MVP, but explain only a fraction of cases.
• Genome-wide association studies indicate a significant role for common genetic variants in MVP development.
• Potential genetic links between MVP, ventricular arrhythmia, and specific cardiomyopathies are under consideration.

Conclusions:

• Deciphering the complete genetic architecture of MVP remains a significant challenge.
• Genetic data and animal models are crucial for advancing the understanding of MVP pathophysiology.
• Genetic counseling is an important consideration for families affected by MVP.