Diagnosi molecolare di sindrome di Brugada in un giovane atleta mediante il sequenziamento di un pannello multigenico con tecniche di nuova generazione

Mutations in genes driving the molecular pathways that regulate myocardial functions can predispose to many independent cardiopathies and also to sudden cardiac death (SCD) even in asymptomatic subjects. The overlapping clinical signs or symptoms or even silent phenotypes make it difficult to diagnose these diseases, therefore the risk of undiagnosed disease could be high especially in young adults and athletes, which may then incur in SCD. We describe the case of a clinical asymptomatic eight-year-old child, practicing soccer game, who underwent a screening medical examination to undertake the path of an increasing physical activity to become a competitive athlete, where abnormal signs at ECG indicated a suspicion of an arrhythmogenic heart disease. Molecular screening analysis, to discriminate among the various predisposing gene alterations, was performed using a 75 gene-panel for arrhythmias customized in our laboratory. The child resulted carrier of a loss-of-function mutation in the SCN5A gene (c.1126C>T). About 25% of Brugada patients carry mutations in this gene coding for the cardiac sodium channel. The loss-of-function mutations in SCN5A gene induce alterations of sodium ion conduction in cardiomyocytes, compatible with the Brugada Syndrome. This case report highlights the importance of the implementation of a rapid, sensitive and wide molecular screening to shed light on possible genetic alterations present also in asymptomatic athletes with negative family history, which may often remain undiagnosed, thus exposed to high risk of sudden death.