Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) Probably Caused by DSG2 p.Val149Ile Mutation as Genetic Background When Carrying with Heterozygous PRRT2 p.Arg217ProfsTer8 Mutation: A Case Report

Abstract

Background: ARVC is a rare genetic-related disease characterized by fibrous fat replacement in the ventricular myocardium, caused by mutations in genes encoding for the desmosomal proteins, such as the desmoglein-2 gene (DSG2). It is reported in the literature that other genetic factors may play a role in disease penetrance. Herein, we report a Chinese proband with ARVC, which was probably caused by DSG2 p.Val149Ile mutation as genetic background when carrying heterozygous PRRT2 p.Arg217ProfsTer8 mutation. Case Presentation: A 17-year-old male with a history of paroxysmal kinesigenic dyskinesia (PKD) presented to the hospital for syncope induced by ventricular tachycardia. According to relevant clinical data and the diagnostic criteria of ARVC, a precise positive diagnosis of ARVC was finally made. Gene testing revealed that the patient carried a DSG2 heterozygous missense mutation (NM_001943: exon5: c.445G>A, p.Val149Ile) as well as frameshift mutation of PRRT2 (NM_001256442: exon2: p. Arg217Profs Ter8). Conclusion: This is the first time to report a Chinese proband with ARVC and a history of PKD carrying both DSG2 p. val149ile mutation and PRRT2 p. Arg217ProfsTer8 mutation, which can provide a new direction for gene screening of patients with ARVC and further supplements for its diagnostic criteria.

A Case Report of a Young Patient Presenting With Syncope Secondary to Arrhythmogenic Ventricular Cardiomyopathy

“…ARVC is a rare inherited cardiomyopathy, and the reported incidence varies from 1:1000 to 1:1250 in some studies and 1:1000 to 1:5000 in other studies [ 2 , 3 ]. ARVC is characterized pathologically by fibrofatty replacement of the right ventricular myocardium and clinically by ventricular tachycardia that can result in sudden cardiac death, mostly in young patients and athletes whereas ALVC patients have fibrofatty myocardial replacement affecting the subepicardial layers in the left ventricle [ 5 ].…”

“…Most younger patients do not have any symptoms and may only be diagnosed when they present with a syncopal episode or sudden cardiac arrest [ 2 ]. The commonest cause for fibrous fat replacement of myocardium in patients with ARVC is mutations in genes encoding desmosomal proteins, such as the desmoglein-2 gene (DSG2) [ 3 ]. Other genes found to have alterations in patients with ARVC include plakoglobin (JUP), desmocollin 2 (DSC2), plakophilin 2 (PKP2), and desmoplasia (DSP) [ 3 ].…”

“…The commonest cause for fibrous fat replacement of myocardium in patients with ARVC is mutations in genes encoding desmosomal proteins, such as the desmoglein-2 gene (DSG2) [ 3 ]. Other genes found to have alterations in patients with ARVC include plakoglobin (JUP), desmocollin 2 (DSC2), plakophilin 2 (PKP2), and desmoplasia (DSP) [ 3 ]. It is most commonly diagnosed on post-mortem examination following the death of an individual; however, younger patients may also present with sustained ventricular tachycardia, left-sided, right-sided, or biventricular failure [ 1 ].…”