Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy

Abstract

Has referral for genetic evaluation of inherited cardiomyopathies and arrhythmias become a routine part of your clinical practice yet? After several decades of molecular genetic research into the causes of inherited forms of heart disease, the field of cardiovascular genetics is rapidly growing. The pace of progress has accelerated even further in the setting of remarkable technologies that have lowered the costs and increased the speed with which gene sequencing can be performed. Two articles in the curent issue of Circulation point out both the benefits and challenges that are inherent in this evolving new era of genetic characterization as applied to arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), with particular attention to how this condition runs in families.1,2 Articles see p 2690 and 2701 The largest published series to date arises from a Dutch team of investigators. Cox et al1 present the genetic and phenotypic aspects of 149 ARVD/C probands, along with several important novel pieces of information. They emphasize the importance of family member evaluations by characterization of an additional 302 individuals at risk of inheriting a genetic predisposition to ARVD/C. Among 282 family members who were without any symptoms, 42 (15%) were diagnosed with ARVD/C, facilitating empirical treatment and close follow-up in an attempt to prevent life-threatening manifestations. They highlight the high prevalence of prolongation of the terminal activation duration on ECGs among family members with desmosome gene mutations. Their data help to clarify prior reports of 3 gene variants that were previously considered pathogenic, but now should be considered nonpathogenic. Notably, they included in their methods a technique called multiplex ligation-dependent probe amplification to identify large insertions, deletions, or gene rearrangements that would not be picked up with traditional DNA sequencing.3 Although rare, 3 of the 149 probands (2%) had such a mutation …