Abstract 12326: Revised 2010 Task Force Criteria for ARVD/C Diagnosis Promote Inclusion of Non-Desmosomal Mutation Carriers
Introduction: Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C) is usually associated with desmosomal gene mutations. In 40% of ARVD/C patients, fulfilling in 2010 revised Task Force Criteria (TFC), no pathogenic desmosomal mutation is found. However, non-desmosomal mutations may be involved.
Aim: Assessment of contribution of gene mutations in Phospholamban (PLN) to ARVD/C diagnosis according to revised 2010 TFC.
Methods: In 143 Dutch patients (106 males, age 50 ±13 years) with either proven (fulfilment of 2010 TFC, n=139) or probable (1 major + 1 minor, or 3 minor criteria, n=4) ARVD/C, all 5 known desmosomal genes were screened for mutations: PKP2, DSP, DSC2, DSG2, JUP. When negative, the non-desmosomal gene PLN was evaluated. After genetic analysis, we compared phenotypic characteristics in desmosomal versus non-desmosomal (PLN) mutation carriers.
Results: No desmosomal mutation identified in 55/143 (38%) ARVD/C patients. At this stage, 12 out of 18 ARVD/C patients additionally screened for PLN mutations carried the Dutch founder mutation c.40_42delAGA (p.Arg14del). All 4 patients with probable and 8 with proven ARVD/C were c.40_42delAGA positive. PLN mutation carriers (n=12) frequently had low voltage ECG (8/12) and inverted T in V4-V6 (6/12). Only 7% of desmosomal mutation carriers had inverted T in V4-V6. No statistical differences were found in structural, depolarization and repolarization abnormalities, and in ventricular arrhythmias between desmosomal and non-desmosomal groups, although inverted T in V1-V3 occurred more frequently in desmosomal mutation carriers (76 vs. 44% p0.055). Revised TFC analysis included 21/139 proven ARVD/C patients that did not meet the previous 1994 TFC, including 2 PLN mutation carriers. All 4 probable ARVD/C patients would meet 2010 TFC if a major criterion (pathogenic mutation associated with ARVD/C) would be assigned to a PLN mutation.
Conclusion: Substantial contribution of PLN mutation to ARVD/C diagnosis by revised 2010 TFC. In 16% (8/51) of genetically unexplained, proven ARVD/C patients this non-desmosomal mutation was found. Phenotypic characterization displays low voltage ECG and inverted T in left-precordial leads in PLN mutation carriers.
- © 2011 by American Heart Association, Inc.