Arrhythmogenic cardiomyopathy in children: genetic basis and phenotypic manifestations. A single center experience

Aim. To investigate clinical manifestations, phenotypic variants, genetic features, and outcomes in children with arrhythmogenic cardiomyopathy (ACM).

Methods. The study group consisted of 24 patients (< 18 years of age) with ACM, who were under observation from 2011 to 2024. The median age at ACM diagnosis was 13 years [12-15]. The following data were analyzed: complaints and medical history, laboratory parameters (biochemical markers of inflammation and serum myocardial damage mar­ kers, NT-proBNP levels), electrocardiogram, Holter monitoring, echocardiography results, cardiac magnetic resonance imaging, selective coronary angiography, histological and molecular genetic studies. The median follow-up duration for ACM patients was 27 months [16.5-38].

Results. All patients were unrelated probands. All children presented with asymptomatic ventricular arrhythmias (VA) as the initial manifestation of the disease, 23 (95.8%) patients had complaints: palpitations in 21 (87.5%) children, syncope in 14 (58.3%) children, heart failure symptoms in 12 (50.0%), and isolated chest pain in 4 (16.7%) patients. 5 (20.8%) children had a “hot” phase. Analysis of arrhythmic data revealed several features of ACM in childhood: VAs were polymorphic, daily VA density was less than 20% at the time of diagnosis, presence of late ventricular potentials in most patients, and several criteria from the «repolarization abnormalities» group had low informativeness. During follow-up, 9 (37.5%) children had the right-dominant ACM, 7 (29.9%) had ACM with left ventricle involvement, and 8 (33.3%) had biventricular form. Desmosomal mutations were found in 16 children (66.7%), non-desmosomal gene variants in 8 patients (33.3%).

Conclusion. It has been shown that ACM can manifest at an early age and is associated with the development of arrhythmic events and/or severe heart failure. Increasing awareness among physicians about the early onset of ACM is crucial for timely treatment of heart failure, prevention of sudden cardiac death, and family screening.

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