Clinical phenotype and diagnosis of arrhythmogenic right ventricular cardiomyopathy in pediatric patients carrying desmosomal gene mutations

Heart Rhythm. 2011 Nov;8(11):1686-95. doi: 10.1016/j.hrthm.2011.06.026. Epub 2011 Jun 30.

Abstract

Background: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease carrying a risk of sudden death. Information about the clinical features during childhood and the age at disease onset is scanty.

Objective: The aim of the study was to describe the ARVC phenotype as its initial clinical manifestation in a pediatric population (<18 years) with desmosomal gene mutations.

Methods: Fifty-three ARVC desmosomal gene mutation carriers (mean age 12.3 ± 3.9 years) were investigated by electrocardiogram (ECG), signal-averaged ECG, 24-hour Holter, echocardiogram, and contrast-enhanced cardiac magnetic resonance (CMR).

Results: None of the children ≤10 years old fulfilled the 1994 criteria, as opposed to six (33%) aged 11-14 years and eight aged >14 years (42%). At the end of follow-up (9 ± 7 years), 21 (40%) fulfilled the 1994 diagnostic criteria (mean age 16 ± 4 years). By using the 2010 criteria in subjects aged ≤18 years, 53% were unaffected, versus 62% by using the traditional criteria. More than two-thirds of affected subjects had moderate-severe forms of the disease. Contrast-enhanced CMR was performed in 21 (40%); of 13 unaffected gene mutation carriers, six showed ARVC morphological and/or tissue abnormalities.

Conclusion: In pediatric ARVC mutation carriers, a diagnosis was achieved in 40% of cases, confirming that the disease usually develops during adolescence and young adulthood. The 2010 modified criteria seem to be more sensitive than the 1994 ones in identifying familial pediatric cases. Contrast-enhanced CMR can provide diagnostic information on gene mutation carriers not fulfilling either traditional or modified criteria. Management of asymptomatic gene mutation carriers remains the main clinical challenge.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Arrhythmogenic Right Ventricular Dysplasia / diagnosis
  • Arrhythmogenic Right Ventricular Dysplasia / genetics*
  • Child
  • DNA / analysis*
  • DNA Mutational Analysis
  • Desmosomes / genetics*
  • Diagnosis, Differential
  • Echocardiography*
  • Electrocardiography*
  • Female
  • Follow-Up Studies
  • Humans
  • Magnetic Resonance Imaging, Cine / methods*
  • Male
  • Mutation*
  • Pedigree
  • Phenotype
  • Prognosis
  • Retrospective Studies

Substances

  • DNA