The heart in m.3243A>G carriers

Herz. 2020 Jun;45(4):356-361. doi: 10.1007/s00059-018-4739-6. Epub 2018 Aug 20.

Abstract

Objectives: Little is known about cardiac involvement in m.3243A>G variant carriers. Thus, this study aimed to assess type and frequency of cardiac disease in symptomatic and asymptomatic m.3243A>G carriers.

Methods: Systematic literature review.

Results: The m.3243A>G variant may manifest phenotypically as mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), maternally inherited diabetes and deafness (MIDD), myoclonic epilepsy with ragged red fiber (MERRF), Leigh syndrome, or MELAS/KSS (Kearns-Sayre syndrome) overlap. Only few systematic studies which prospectively investigated m.3243A>G carriers for cardiac involvement were found. Cardiac abnormalities reported in m.3243A>G carriers include myocardial abnormalities, arrhythmias, or conduction defects. Myocardial abnormalities include myocardial thickening, hypertrophic cardiomyopathy, dilated cardiomyopathy, noncompaction, myocardial fibrosis, systolic dysfunction, heart failure, or arterial hypertension. Arrhythmias reported in m.3243A>G carriers include paroxysmal supraventricular or ventricular arrhythmias, including sinus tachycardia, atrial fibrillation and nonsustained ventricular tachycardia, and sudden cardiac death. Conduction defects in this group of patients include Wolff-Parkinson-White syndrome and left/right bundle branch block. Asymptomatic m.3243A>G carriers usually do not develop clinical or subclinical cardiac disease.

Conclusions: Cardiac involvement in m.3243A>G carriers has been only rarely systematically studied, which is perhaps why the incidence of cardiac diseases in MELAS is lower than would be expected. Myocardial abnormalities are much more frequent than arrhythmias or conduction defects. All symptomatic and asymptomatic m.3243A>G carriers should be systematically investigated for cardiac disease.

Keywords: Arrhythmias; Cardiomyopathy; DNA, mitochondrial; MELAS syndrome; Maternally inherited diabetes and deafness.

Publication types

  • Review

MeSH terms

  • DNA, Mitochondrial
  • Deafness*
  • Diabetes Mellitus, Type 2*
  • Heart Diseases* / genetics
  • Humans
  • MELAS Syndrome*
  • Mitochondrial Diseases*
  • Myocardium / pathology

Substances

  • DNA, Mitochondrial

Supplementary concepts

  • Noninsulin-dependent diabetes mellitus with deafness