TY - JOUR
T1 - The role of genetics in cardiovascular disease
T2 - Arrhythmogenic cardiomyopathy
AU - James, Cynthia A.
AU - Syrris, Petros
AU - Van Tintelen, J. Peter
AU - Calkins, Hugh
N1 - Publisher Copyright:
© 2020 Published on behalf of the European Society of Cardiology. All rights reserved.
PY - 2020/4/7
Y1 - 2020/4/7
N2 - Arrhythmogenic cardiomyopathy (ACM) is a heritable cardiomyopathy characterized by frequent ventricular arrhythmias and progressive ventricular dysfunction. Risk of sudden cardiac death is elevated in ACM patients and can be the presenting symptom particularly in younger individuals and athletes. This review describes current understanding of the genetic architecture of ACM and molecular mechanisms of ACM pathogenesis. We consider an emerging threshold model for ACM inheritance in which multiple factors including pathogenic variants in known ACM genes, genetic modifiers, and environmental exposures, particularly exercise, are required to reach a threshold for disease expression. We also review best practices for integrating genetics-including recent discoveries-in caring for ACM families and emphasize the utility of genotype for both management of affected individuals and predictive testing in family members.
AB - Arrhythmogenic cardiomyopathy (ACM) is a heritable cardiomyopathy characterized by frequent ventricular arrhythmias and progressive ventricular dysfunction. Risk of sudden cardiac death is elevated in ACM patients and can be the presenting symptom particularly in younger individuals and athletes. This review describes current understanding of the genetic architecture of ACM and molecular mechanisms of ACM pathogenesis. We consider an emerging threshold model for ACM inheritance in which multiple factors including pathogenic variants in known ACM genes, genetic modifiers, and environmental exposures, particularly exercise, are required to reach a threshold for disease expression. We also review best practices for integrating genetics-including recent discoveries-in caring for ACM families and emphasize the utility of genotype for both management of affected individuals and predictive testing in family members.
KW - Arrhythmogenic cardiomyopathy
KW - Arrhythmogenic right ventricular cardiomyopathy
KW - Cardiovascular genetics
KW - Genetic counselling
UR - http://www.scopus.com/inward/record.url?scp=85083003360&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85083003360&partnerID=8YFLogxK
U2 - 10.1093/eurheartj/ehaa141
DO - 10.1093/eurheartj/ehaa141
M3 - Review article
C2 - 32191298
AN - SCOPUS:85083003360
SN - 0195-668X
VL - 41
SP - 1393
EP - 1400
JO - European heart journal
JF - European heart journal
IS - 14
ER -