Abstract   Some studies have shown the association between ventricular and atrial arrhythmias, dilated cardiomyopathy and the R222Q mutation of the SCN5A gene. The mutation causes impaired activation of the sodium channel, the genesis of extrasystoles and the development of dilated cardiomyopathy; both respond better to antiarrhythmic therapy with flecainide and amiodarone than therapy for heart failure. Other studies have shown the efficacy of hydroquinidine. Purpose of the Study To observe the clinical characteristics and the response to drug therapy of pediatric subjects carrying the R222Q mutation. Materials and methods we observed subjects received at our centre for arrhythmias, carriers of the R222Q variant, subjected to ECG, Echocardiogram, Holter, stress test and follow up. Results 4 patients were observed, 3 males and 1 female, with ages ranging from 0 to 12 years. The first patient was familiar with dilated cardiomyopathy and rhythm disturbances; he had arrhythmia already in foetal age, he then developed first and second–degree BAV, junctional rhythm and polyform TVNS. Echocardiography and exercise testing were normal. Arrhythmia control was achieved with flecainide. The second patient, with negative familiarity, from the age of 8 is under observation for polyform ventricular ectopic beats, repetitive, unresponsive to propafenone, flecainide, nadolol and sotalol. Echocardiography showed minimal impairment of the contractile function of the left ventricle. Ventricular extrasystoles did not disappear during exertion. At 15, a defibrillator was implanted and hydroquinidine was associated. The third patient presented with foetal tachyarrhythmias; at the age of 6, atrial tachycardia, well–controlled by sotalol, and ventricular ectopic beats were detected. The fourth patient, a cousin of the previous one, developed repetitive ventricular ectopic beats and periods of atrial and junctional rhythm at 12 years; he responded to flecainide. Conclusions The R222Q mutation of the SCN5A gene is responsible for arrhythmias already from the pediatric age and is expressed with a variable phenotype. Only one patient with therapy–resistant arrhythmia had contractile dysfunction. Dilated cardiomyopathy could be a consequence of a high arrhythmic burden and occur at a later age if the arrhythmia is not treated. An early and genetic diagnosis is essential.