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Molecular biology and the clinical management of arrhythmogenic right ventricular cardiomyopathy/dysplasia
  1. Domenico Corrado1,
  2. Cristina Basso2,
  3. Kalliopi Pilichou2,
  4. Gaetano Thiene2
  1. 1Inherited Arrhythmogenic Cardiomyopathy Unit, Department of Cardiac, Thoracic and Vascular Sciences, University of Padua Medical School, Padua, Italy
  2. 2Cardiovascular Pathology, Department of Medico-Diagnostic Sciences and Special Therapies, University of Padua Medical School, Padua, Italy
  1. Correspondence to Domenico Corrado, Department of Cardiac, Thoracic and Vascular Sciences, Via Giustiniani, 2-35121 Padova, Italy; domenico.corrado{at}unipd.it

Abstract

In the last two decades the extraordinary advances in molecular biology of arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) have provided significant insights into our understanding of the disease aetiology by showing that it is a genetic disorder of the cardiac desmosomes and that interactions between mechanical disruption of cell–cell adhesion and defects of desmosomal-mediated intracellular signalling are likely to be involved in the pathogenesis of the ARVC/D phenotype. The discovery of the causative genes for ARVC/D offers the possibility of identifying genetically-affected individuals before potentially malignant clinical phenotype occurs. Moreover, the evaluation of abnormal localisation of desmosomal proteins by immunohistochemical analysis on endomyocardial biopsy samples represents a promising test for ARVC/D diagnosis. Early detection of ARVC/D and preventive therapy of young individuals at highest risk of experiencing sudden cardiac death may be improved by molecular genetic screening within affected families and may alter the clinical management of patients. At present, however, the clinical use of genotyping is limited by the incomplete knowledge of causative mutations and the complex genetic background of the disease, which accounts for the incomplete penetrance and the marked variability of the phenotype expression. This review addresses the advances in the molecular biology of ARVC/D, with particular reference to the genetic basis of the disease, and how these advances have impacted on understanding the disease pathogenesis, on diagnosis and in establishing management strategies.

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Footnotes

  • Funding This work was supported by the Ministry of Health, Rome; Fondazione Cariparo, Padova and Rovigo; Registry of Cardio-cerebro-vascular Pathology, Veneto Region, Venice, Italy; and TELETHON, Rome GGP09293.

  • Competing interests None.

  • Provenance and peer review Commissioned; externally peer reviewed.

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