CONGRESS ABSTRACT

Introduction: Genetic testing is an increasingly used diagnostic tool in Cardiology, also in pediatric age. Aim of the study: To evaluate the use and results of genetic testing in the pediatric population referred to our Cardiology Center. Materials and methods: We retrospectively reviewed 210 patients aged from a few days of life to 17 years who were referred to our Pediatric Cardiology Center and underwent genetic testing between 2015 and 2024. Results: Genetic testing was performed in 66.2% of cases for suspected cardiomyopathy or channelopathy, in 18.1% of cases for suspected syndromic conditions including extracardiac features, and in 15.7% of cases because of a family history of heart disease, when a pathogenic variant had been identified in a first-degree relative. The type of analysis varied according to the indication: targeted testing for a known familiar variant, SNP array in cases of suspected microdeletion/microduplication syndromes, targeted gene panel sequencing, and clinical exome analysis. According to ACMG criteria, variants are classified into five categories based on pathogenicity score: benign, likely benign, variants of uncertain significance (VUS), likely pathogenic, and pathogenic. In patients evaluated for suspected syndromes, genetic testing was positive in 36.8% of cases and showed variants of uncertain significance in 5.3%. In patients with suspected cardiomyopathy or channelopathy, genetic testing was negative in 36.7% of cases, positive in 28%, and revealed variants of uncertain significance in 35.3%. In one case, a variant initially classified as uncertain for long QT syndrome was reclassified as pathogenic after several years. In another case, a pathogenic variant for long QT syndrome was identified in a neonate with a negative phenotype who underwent testing as part of a screening program. Additionally, a 9-year-old patient who underwent exome sequencing for neurodevelopmental disorders was found to carry a pathogenic variant in the RYR2 gene, in the absence of cardiac signs or symptoms. Conclusions: new sequencing technologies increase the detection rate of genetic diseases but also raise the risk of incidental findings. Conversely, in some cases, despite a strong clinical suspicion of a genetically based cardiopathy, a diagnosis may not be reached due to insufficient data in the literature. In such cases, repeating the analysis after several years and frequently re-querying research databases is recommended.