The Genetic Origin of Atrioventricular Conduction Disturbance in Humans

  1. Derek J. Chadwick Organizer and
  2. Jamie Goode
  1. D. Woodrow Benson

Published Online: 7 OCT 2008

DOI: 10.1002/0470868066.ch15

Development of the Cardiac Conduction System: Novartis Foundation Symposium 250

Development of the Cardiac Conduction System: Novartis Foundation Symposium 250

How to Cite

Benson, D. W. (2008) The Genetic Origin of Atrioventricular Conduction Disturbance in Humans, in Development of the Cardiac Conduction System: Novartis Foundation Symposium 250 (eds D. J. Chadwick and J. Goode), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/0470868066.ch15

Author Information

  1. Division of Cardiology, OSB 4, Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229-3039, USA

Publication History

  1. Published Online: 7 OCT 2008
  2. Published Print: 20 JUN 2003

Book Series:

  1. Novartis Foundation Symposia

Book Series Editors:

  1. Novartis Foundation

ISBN Information

Print ISBN: 9780470850350

Online ISBN: 9780470868065

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Summary

Atrioventricular (AV) conduction disturbance (block) describes impairment of the electrical continuity between the atria and ventricles. Clinical classification of AV block has utilized biophysical characteristics, usually the extent (1st, 2nd, 3rd degree) and site of block (above or below His bundle recording site). The genetic significance of this classification is not known. In some cases AV block occurrence is associated with intrauterine exposure to maternal antibody (anti-Ro, anti-La), and other cases are associated with injury (e.g. surgery). Based on familial clustering of idiopathic AV block, a genetic cause has also been suspected. Published pedigrees show autosomal dominant inheritance, and associated heart disease is common (e.g. congenital heart malformation, cardiomyopathy, etc.). The latter finding is not unexpected given the common origin of working myocytes and elements of the specialized conduction system. Using genetic models incorporating reduced penetrance (presence of disease genotype in absence of phenotype), variable expressivity (presence of a disease genotype with variable phenotypes) and genetic heterogeneity (similar phenotypes, different disease genotypes), molecular genetic causes of AV block are being identified. These findings are significant as they provide insight into the molecular basis of a clinical condition previously defined only by biophysical characteristics.