Phenotypic Manifestations of Cardiomyopathy in Children

Study Questions:

What are the phenotypic, genotypic, and outcome characteristics of the population of pediatric patients diagnosed with arrhythmogenic cardiomyopathy (AC) at the Boston Children’s Hospital?


This is a descriptive single-center retrospective cohort study of patients <21 years of age diagnosed with or screened (due to family history) for AC. Diagnosis was made using 2010 arrhythmogenic right ventricular cardiomyopathy (ARVC) Task Force Criteria or proposed criteria for left-dominant cases. Patients were subdivided into right ventricular (RV), left ventricular (LV), and biventricular (BiV) disease subtypes. Genetic sequencing was also performed in most patients.


In total, 47 patients were identified, with 32 having manifest disease and 15 family members not meeting diagnostic criteria. The mean age of diagnosis for the three subtypes ranged from 12 to 16 years, with the BiV affected patients being generally younger. Ventricular arrhythmias occurred more often in the RV subtype, with up to 75% of them experiencing cardiac arrest or ventricular tachycardia. The RV subtype was also completely associated with genetic mutations affecting PKP2, while the LV and BiV subtypes were associated with a variety of candidate genes. Seven of the identified patients, including three each in the LV and BiV subgroups, had evidence of myocardial inflammation. Extensive additional results data are also included in the manuscript.


The authors concluded that AC in children is a highly varied disease with significant overlap with other diagnoses.


In this highly descriptive and detailed cohort presentation, DeWitt and colleagues contribute to the growing body of data on pediatric variations in a typically “adult” cardiac disease. One of the many details a reader might pull from this study is the potential difficulty in accurately diagnosing AC. While the RV subtype diagnostic criteria are well established, the authors based LV and BiV types on “suggested criteria.” Notably, almost half of the patients in the LV group had LMNA mutations, which others have described as phenocopies or overlap syndromes not consistent with ARVC. Adding to the challenge are the six patients in the LV or BiV groups with evidence of inflammation, where differentiation from myocarditis may be elusive. While the proposition that syndrome overlap may be accurate, it remains possible that diagnostic criteria require refinement to consider genotype and/or age.

Clinical Topics: Arrhythmias and Clinical EP, Congenital Heart Disease and Pediatric Cardiology, Heart Failure and Cardiomyopathies, Implantable Devices, Genetic Arrhythmic Conditions, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, CHD and Pediatrics and Arrhythmias, CHD and Pediatrics and Prevention, Acute Heart Failure

Keywords: Adolescent, Arrhythmias, Cardiac, Arrhythmogenic Right Ventricular Dysplasia, Cardiomyopathies, Genotype, Heart Arrest, Heart Failure, Inflammation, Mutation, Myocarditis, Pediatrics, Phenotype, Tachycardia, Ventricular

< Back to Listings