title: Molecular mechanisms of inherited ventricular arrhythmias.
abstract: BACKGROUND
  Inherited ventricular arrhythmias such as the long QT syndrome (LQTS), Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia (CPVT), idiopathic ventricular fibrillation (VF), and arrhythmogenic right ventricular cardiomyopathy (ARVC) account for a relevant proportion of sudden cardiac death cases in young patients cohorts. The detailed pathogenetic mechanisms of inherited ventricular arrhythmias are still poorly understood because systematic investigations are difficult to perform due to low patient numbers and the lack of appropriate experimental models. However, recent advances in research and science have identified a genetic background for many of these diseases.
  In LQTS, various mutations in different genes encoding for cardiac potassium and sodium channel proteins have been identified ("channelopathy"), and initial progress in genotype-phenotype correlation is made. Mutations in the cardiac sodium channel gene have also been identified in a subset of patients with Brugada syndrome, whereas a genetic background has not yet been demonstrated in idiopathic VF and right ventricular outflow-tract tachycardia (RVO-VT). Very recently, mutations in the cardiac ryanodine receptor gene have been identified in CPVT and in a subgroup of patients with ARVC. Although several chromosomal loci were suggested, no other responsible genes or mutations have been found in autosomal dominant forms of ARVC. However, in Naxos disease, a recessive form of ARVC with coexpression of palmoplantar keratoderma and woolly hair, a mutation in the plakoglobin gene has recently been discovered, thus underscoring the potential role of genetic alterations in cytoskeletal proteins in ARVC.
  
  
  CONCLUSIONS
  In the next years, significant progress in the genetic diagnosis pathophysiologic understanding of disease mechanisms, genotype-phenotype correlation, and the development of gene- or target-directed treatment strategies can be expected in the field of inherited ventricular arrhythmias.
  
  
  CONCLUSIONS
  This review summarizes the current knowledge of the molecular mechanisms, including aspects of pathoanatomy, autonomic innervation, genetics, and genotype-phenotype correlations with their potential implications for diagnosis and treatment of inherited ventricular arrhythmias.
authors.affiliation: Department of Cardiology and Angiology, Institute for Arteriosclerosis Research, University of Münster, Germany. wichtet@uni-muenster.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Wichter
authors.forename: Eric
authors.initials: E
authors.lastname: Schulze-Bahr
authors.forename: Lars
authors.initials: L
authors.lastname: Eckardt
authors.forename: Matthias
authors.initials: M
authors.lastname: Paul
authors.forename: Bodo
authors.initials: B
authors.lastname: Levkau
authors.forename: Matthias
authors.initials: M
authors.lastname: Meyborg
authors.forename: Michael
authors.initials: M
authors.lastname: Schäfers
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Haverkamp
authors.forename: Günter
authors.initials: G
authors.lastname: Breithardt
mesh_terms: D004252:DNA Mutational Analysis; D016757:Death, Sudden, Cardiac / Q000209:etiology*; D004562:Electrocardiography; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D007473:Ion Channels / Q000235:genetics; D010641:Phenotype; D017180:Tachycardia, Ventricular / Q000175:diagnosis / Q000235:genetics*
chemical_list: D007473:Ion Channels