Discussion

Arrhythmogenic cardiomyopathy is a rare genetic cardiac disease associated with ventricular arrhythmias and sudden cardiac death, particularly in young individuals. Although traditionally considered a right ventricle disease, left-dominant and biventricular phenotypes are increasingly recognised. ^{Reference Arbelo, Protonotarios and Gimeno6,Reference Corrado, Perazzolo Marra and Zorzi7} Our patient’s diagnosis was supported by extensive subepicardial late gadolinium enhancement in a characteristic ring-like pattern, documented ventricular arrhythmias, mildly reduced left ventricular systolic function, and identification of a likely pathogenic DSP truncating variant, in the absence of right ventricular involvement, consistent with previous observations. ^{Reference DeWitt, Chandler and Hylind3,Reference Kandhari, Khoury, Behr and Miles8} According to the 2023 European Society of Cardiology guidelines, this phenotype is classified as non-dilated left ventricular cardiomyopathy. ^{Reference Arbelo, Protonotarios and Gimeno6} The patient also fulfills the Padua diagnostic criteria, with two major (structural myocardial abnormalities with a fibrosis pattern and genetic diagnosis) and one minor criterion (history of cardiac arrest due to ventricular tachycardia). ^{Reference Corrado, Anastasakis and Basso9} Current guidelines emphasise the central role of cardiac MRI in diagnosis, establishing late gadolinium enhancement—particularly in a ring-like subepicardial pattern—as a hallmark of left ventricular involvement. ^{Reference Arbelo, Protonotarios and Gimeno6,Reference Corrado, Perazzolo Marra and Zorzi7,Reference Corrado, Anastasakis and Basso9,Reference Corrado, Zorzi and Cipriani10} Importantly, cardiac magnetic resonance findings played a central role in phenotype recognition, as classical baseline electrocardiographic abnormalities and significant ventricular ectopy burden, were absent. These findings highlight the limitations of traditional diagnostic criteria in paediatric patients and reinforce the increasing importance of multimodality imaging and genetic testing in early diagnosis.

Arrhythmogenic cardiomyopathy shows age-related penetrance, with symptoms typically appearing in adulthood. However, paediatric presentations, although uncommon, are frequently associated with a high arrhythmic risk. ^{Reference Moisa, Spoiala and Cinteza1} In this case, sudden cardiac arrest was the initial manifestation, illustrating the unpredictable and potentially catastrophic nature of the disease. Importantly, physiologic age-related electrocardiogram variations further limit the reliability of standard diagnostic criteria in this challenging population. ^{Reference Kofeynikova, Alekseeva and Vershinina2}

DSP cardiomyopathy has emerged as a distinct clinical entity within the disease spectrum, characterised by extensive myocardial fibrosis, frequent left ventricular involvement, inflammatory myocardial injury episodes, and high arrhythmic risk. ^{Reference DeWitt, Chandler and Hylind3,Reference Kandhari, Khoury, Behr and Miles8,Reference Martini, Parodi and Marinas11} Truncating DSP variants, in particular, have been associated with more severe phenotypes and fulminant arrhythmic disease progression. ^{Reference Westphal, Krafft and Biller12} Genetic testing confirmed a novel heterozygous DSP variant [c.6948C>A, p.(Tyr2316*)], classified as likely pathogenic, which, to our knowledge, has not been previously reported. The early and severe presentation in the index patient, along with significant myocardial involvement in her father and sister, supports the pathogenic relevance of this variant and suggests high penetrance and rapid disease progression. An additional diagnostic challenge in DSP cardiomyopathy is its overlap with myocarditis, particularly in women, although the exact pathophysiological mechanism underlying this association remains to be elucidated. ^{Reference Westphal, Krafft and Biller12,Reference Scheel, Murray and Tichnell13} These episodes, frequently referred to as inflammatory “hot phases,” may present with chest pain, troponin elevation, ventricular arrhythmias, and cardiac magnetic resonance abnormalities suggestive of acute myocarditis. ^{Reference Martini, Parodi and Marinas11,Reference Wang, Murray and Tichnell14,Reference Brandão, Bariani, Rigato and Bauce15} In our patient, troponin elevation was observed following sudden cardiac arrest; however, the absence of myocardial oedema, the specific ring-like subepicardial fibrosis pattern, and the identification of the same variant in multiple affected family members favoured the diagnosis of DSP-related arrhythmogenic cardiomyopathy. Recognition of this overlap is clinically relevant, as recurrent inflammatory episodes may contribute to progressive fibrosis and arrhythmic risk. ^{Reference Brandão, Bariani, Rigato and Bauce15}

Family screening is essential to pursue risk stratification, genetic counselling, and implementation of preventive strategies, as recommended by current guidelines. ^{Reference Arbelo, Protonotarios and Gimeno6} This approach was adopted in our centre, with genetic testing of the patient’s family identifying the same DSP variant in her father and sister. Management of arrhythmogenic cardiomyopathy focuses on preventing recurrent arrhythmias and sudden cardiac arrest. Cardioverter-defibrillator implantation is the cornerstone of therapy in high-risk patients, particularly those with prior cardiac arrest or DSP truncating variants. ^{Reference Arbelo, Protonotarios and Gimeno6,Reference Kandhari, Khoury, Behr and Miles8}

This case underscores the importance of early recognition of the disease in paediatric patients, in whom symptoms may be absent until a catastrophic event occurs. It also highlights the value of cardiac MRI and genetics in establishing the diagnosis and guiding clinical management. Finally, the identification of a novel DSP truncating variant emphasises the need for further research into genotype–phenotype correlations and disease mechanisms, including the role of inflammatory “hot phases” in disease progression. Improved understanding of these factors may enhance diagnostic accuracy and inform more effective therapeutic strategies, ultimately improving patient and family outcomes.