The phenotypic and genetic features of arrhythmogenic cardiomyopathy in the pediatric population

Olga Kofeynikova; Daria Alekseeva; Tatiana Vershinina; Svetlana Fetisova; Olga Peregudina; Tatiana Kovalchuk; Elena Yakovleva; Polina Sokolnikova; Alexandra Klyushina; Kseniia Chueva; Anna Kostareva; Tatiana Pervunina; Elena Vasichkina

doi:10.3389/fcvm.2023.1216976

The phenotypic and genetic features of arrhythmogenic cardiomyopathy in the pediatric population

Front Cardiovasc Med. 2023 Sep 15:10:1216976. doi: 10.3389/fcvm.2023.1216976. eCollection 2023.

Affiliations

¹ World-Class Research Centre for Personalized Medicine, Almazov National Medical Research Centre, Saint Petersburg, Russia.
² Department of Pediatric Cardiology, Almazov National Medical Research Centre, Saint Petersburg, Russia.
³ Institute of Molecular Biology and Genetics, Almazov National Medical Research Centre, Saint Petersburg, Russia.
⁴ Department of Women's and Children's Health and Center for Molecular Medicine, Karolinska Institutet (KI), Solna, Sweden.
⁵ Institute of Perinatology and Pediatrics, Almazov National Medical Research Centre, Saint Petersburg, Russia.

Abstract

Introduction: The present study aimed to describe the phenotypic features and genetic spectrum of arrhythmogenic cardiomyopathy (ACM) presented in childhood and test the validity of different diagnostic approaches using Task Force Criteria 2010 (TFC) and recently proposed Padua criteria.

Patients and methods: Thirteen patients (mean age at diagnosis 13.6 ± 3.7 years) were enrolled using "definite" or "borderline" diagnostic criteria of ACM according to the TFC 2010 and the Padua criteria in patients <18 years old. Clinical data, including family history, 12-lead electrocardiogram (ECG), signal-averaged ECG, 24-h Holter monitoring, imaging techniques, genetic testing, and other relevant information, were collected.

Results: All patients were classified into three variants: ACM of right ventricle (ACM-RV; n = 6, 46.1%), biventricular ACM (ACM-BV; n = 3, 23.1%), and ACM of left ventricle (ACM-LV; n = 4, 30.8%). The most common symptoms at presentations were syncope (n = 6; 46.1%) and palpitations (n = 5; 38.5%). All patients had more than 500 premature ventricular contractions per day. Ventricular tachycardia was reported in 10 patients (76.9%), and right ventricular dilatation was registered in 8 patients (61.5%). An implantable cardiac defibrillator was implanted in 61.5% of cases, and three patients with biventricular involvement underwent heart transplantation. Desmosomal mutations were identified in 8 children (53.8%), including four patients with PKP2 variants, two with DSP variants, one with DSG2 variant, and one with JUP. Four patients carried compound heterozygous variants in desmosomal genes associated with left ventricular involvement.

Conclusion: Arrhythmias and structural heart disease, such as chamber dilatation, should raise suspicion of different ACM phenotypes. Diagnosis of ACM might be difficult in pediatric patients, especially for ACM-LV and ACM-BV forms. Our study confirmed that using "Padua criteria" in combination with genetic testing improves the diagnostic accuracy of ACM in children.

Keywords: Padua criteria; arrhythmogenic cardiomyopathy; children; sudden cardiac death; task force criteria; ventricular arrhythmia.

Grants and funding

This work was financially supported by the Ministry of Science and Higher Education of the Russian Federation (Agreement No. 075-15-2022-301).