Genetic Characteristics of Children and Adolescents with Long QT Syndrome Diagnosed by School-Based Electrocardiographic Screening Programs Running title: Yoshinaga et al.; Genetic characteristics of screened LQTS patients

Background A school-based electrocardiographic screening program has been developed in Japan. However, few data are available regarding the genetic characteristics of pediatric patients with long QT syndrome (LQTS) who were diagnosed by this program. Methods and Results A total of 117 referred to our centers for genetic testing were the subjects. Of these, 69 subjects diagnosed by the program formed the screened group. A total of 48 subjects were included in the clinical group and were diagnosed with LQTS-related symptoms, familial study, or by chance. Mutations were classified as radical, of high probability of pathogenicity, or of uncertain significance. Two subjects in the clinical group died. Genotypes were identified in 50 (72%) and 23 (48%) of subjects in the screened and clinical groups, respectively. Of the KCNQ1 or KCNH2 mutations, 31 of 33 (94%) in the screened group and 15 of 16 (94%) in the clinical group were radical and/or of high probability of pathogenicity. Prevalence of symptoms before (9/69 vs. 31/48, p<0.0001) and after (12/69 vs. 17/48, p=0.03) diagnosis was significantly lower in the screened group compared with the clinical group, although the QTc values, family history of LQTS, sudden death, and follow-up periods were not different between the groups. Conclusions These data suggest that the screening program may be effective for early diagnosis of LQTS that may allow intervention before symptoms. In addition, screened patients should have follow-up equivalent to clinically-identified patients.