PO63 Genetic Diagnostic Yield in Children with Sudden Cardiac Death/Sudden Cardiac Arrest without Clear Phenotype

Background Sudden cardiac death/arrest (SCD/SCA) in childhood are frequently associated with inherited arrhythmogenic syndromes (IAS). Many paediatric SCD/SCA cases remain without an overt phenotype due to incomplete penetrance and variable expressivity. Genetic testing has become essential for uncovering underlying causes, facilitating diagnosis, family risk stratification, and preventive interventions. Purpose This study aims to evaluate the diagnostic yield of genetic testing in children with SCD/SCA lacking a clear phenotypic diagnosis, at the largest referral center in Spain. Methods We conducted a retrospective review of childhood SCD/SCA cases (≤18 years) referred to our hospital from 2014 to 2024, without a clear initial clinical diagnosis. All subjects underwent genetic testing using a comprehensive panel of 116 genes implicated in IAS. Clinical and demographic data were systematically collected, and patients were followed for a median of 6.7 years. Results Eighty-six patients (65% male) with a median age of 6.9 years at the event were included. An IAS pathogenic/likely pathogenic variant was identified in 33% (n=28) of cases: 15% (n=13) in genes associated with channelopathies (median age 8 years) and 17% (n=15) in genes associated with cardiomyopathies (median age 14 years). No definitive genetic causative variants were found in 67% of patients (n=58), 54% had inconclusive genetic findings and 13% were negative. Conclusions Genetic testing yields relevant information that helps achieve a precise diagnosis in pediatric SCD/SCA cases without an initial clinical phenotype. Nonetheless, a fraction of cases remains genetically unresolved, highlighting the imperative for ongoing research, functional characterization of variants, integration of clinical and genètic data, and systematic family cascade screening to optimize diagnosis and prevention.