scholarly journals Prevalence and Potential Genetic Determinants of Young Sudden Unexplained Death Victims with Suspected Arrhythmogenic Mitral Valve Prolapse Syndrome

2021 ◽  
Author(s):  
John R. Giudicessi ◽  
Joseph J. Maleszewski ◽  
David J. Tester ◽  
Michael J. Ackerman
Keyword(s):  
Mitral Valve ◽  
Mitral Valve Prolapse ◽  
Genetic Determinants ◽  
Sudden Unexplained Death ◽  
Unexplained Death

P4172Prevalence and potential genetic determinants of young sudden unexplained death victims with suspected arrhythmogenic mitral valve prolapse

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
J Giudicessi ◽  
D Tester ◽  
M Ackerman
Keyword(s):  
Mitral Valve ◽  
Mitral Valve Prolapse ◽  
Molecular Mechanisms ◽  
Age At Death ◽  
Genetic Determinants ◽  
Contributing Factors ◽  
Benign Condition ◽  
Sudden Unexplained Death ◽  
Unexplained Death ◽  
Whole Exome

Abstract Background Mitral valve prolapse (MVP) is largely considered a benign condition. Recently, arrhythmogenic MVP, a sudden cardiac death (SCD)-predisposing condition characterized clinically by frequent/complex ventricular arrhythmias likely secondary to prolapsing leaflet-induced fibrosis of the left ventricle (LV), has emerged as an underappreciated cause of sudden unexplained death in the young (SUDY). Objective To determine the prevalence and potential genetic underpinnings of suspected arrhythmogenic MVP in a referral cohort of SUDY cases. Methods In this retrospective necropsy study, the medical records, autopsy reports, and whole exome molecular autopsy (WEMA) results for 77 SUDY victims (27 females; average age at death 20.6±8.9 years) were reviewed. Evidence of myxomatous MVP and concomitant LV pathology were noted. Variants detected in the pre-specified 164 WEMA gene panel with a frequency <0.001 in public exomes were classified using the 2015 American College of Medical Genetics (ACMG) guidelines. Results Overall, 6/77 (7.8%; 2 females; average age at death 20.7±6.9 years) SUDY cases had MVP as the lone abnormal post-mortem finding. The majority had bileaflet involvement (5/6; 83%) and microscopic LV fibrosis (5/6; 83%). Two SUDY cases (33%) were diagnosed with MVP by echocardiography prior to death. No gross hypertrophy, myocyte disarray, or fibrofatty replacement was noted. Unexpectedly, an ACMG pathogenic/likely pathogenic (P/LP) was more likely to be detected in SUDY cases with MVP than those without [3/6 (50%) vs 9/71 (13%); p<0.05]. Interestingly, the three variants identified in MVP-positive SUDY cases localized to genes associated previously with a cardiomyopathy/channelopathy predisposition (p.E1518fsX25-DMD, p.S285N-RYR2, and p.R109X-TTN). Conclusion This WEMA series provides additional evidence that the combination of bileaflet MVP and microscopic LV fibrosis underlies an unexpected number of SUDY cases. Whether P/LP variants in cardiomyopathy/channelopathy-susceptibility genes function as contributing factors or if unrelated, but poorly understood, molecular mechanisms account for the distinct cardiomyopathy-like phenotype observed in arrhythmogenic MVP requires further investigation.

Mitral valve prolapse

1979 ◽  
Vol 15 (2) ◽  
pp. 362
Author(s):  
MH Han ◽  
CK Im ◽  
DR Im ◽  
MC Han
Keyword(s):  
Mitral Valve ◽  
Mitral Valve Prolapse

Features of degenerative mitral valve prolapse in the North East of China: repair characteristics, and short-term follow-up results

2020 ◽  
Vol 68 (5) ◽  
Author(s):  
Silvia Corona ◽  
Paolo Barbier ◽  
Guangyu Liu ◽  
Osafo A. Annoh ◽  
Marcio Scorsin ◽  
...  
Keyword(s):  
Mitral Valve ◽  
Mitral Valve Prolapse ◽  
Short Term ◽  
North East ◽  
The North
Sign in / Sign up

Export Citation Format

Share Document