KCNH2 p.Gly262AlafsTer98: A New Threatening Variant Associated with Long QT Syndrome in a Spanish Cohort.

Long QT syndrome (LQTS) is an inherited (autosomal dominant) channelopathy associated with susceptibility to ventricular arrhythmias due to malfunction of ion channels in cardiomyocytes, that could lead to sudden death (SD). Most pathogenic variants are in the main 3 genes: KCNQ1 (LQT1), KCNH2 (LQT2) and SCN5A (LQT3). Efforts to improve the understanding of the genotype-phenotype relationship are essential to improve the medical clinical practice. In this study, we identified all index patients referred for NGS genetic sequencing due to LQTS, in a Spanish cohort, who were carriers of a new pathogenic variant (KCNH2 p.Gly262AlafsTer98). Genetic and clinical family screening was performed in order to describe its phenotypic characteristics. We identified 22 relatives of Romani ethnicity, who were carriers of the variant. Penetrance reached a 100% and adherence to medical treatment was low. There was a high rate of clinical events, particularly arrhythmic events and SD (1 in every 4 patients presented syncope, 1 presented an aborted SD, 2 obligated carriers suffered SD before the age of 40 and 4 out of 6 carriers of an implantable cardioverter-defibrillator (ICD) had appropriate ICD therapies. Correct adherence to medical treatment in all carriers should be specially encouraged in this population. ICD implantation decision in non-compliant patients, and refusing left cardiac sympathetic denervation, should be carefully outweighed.

Hypertrophic cardiomyopathy and athlete's heart: a tale of two entities.

Sudden death during sports activities, although unfrequent, is a tragic event with great impact on both the general and medical communities. The two commonest conditions leading to sudden cardiac death in young athletes are hyperthrophic cardiomyopathy (HCM), the main cause in the USA, and arrythmogenic right ventricular cardiomyopathy, which is the leading cause in Europe. We report the case of a 17-year-old football player with a pathological electrocardiography (ECG) in the pre-participation screening programme, highly suggestive of HCM, in which ECG study showed a septum thickness of 28 mm. Genetic analysis revealed R 495 W mutation in the 18 exon of the MyBPC3 (myosin-binding protein C) and sports activities were contraindicated. Two years later, septum thickness was 19.5 mm. Usefulness of 12-lead ECG, differential diagnosis between athlete's heart and HCM, and the stratification in patients with HCM are discussed.