0186 : Genotype/phenotype relationship in a large cohort of long QT syndrome patients

Abstract

Introduction Congenital long QT syndrome (LQTS) is a hereditary disease characterized by prolonged QTc and a risk of cardiac arrest. The aim of this study is to report the experience of the referral center of Nantes hospital. Methods Patients were recruited from 19 tertiary centers in France between 1997 and 2014. Clinical data and 12-lead ECG were collected. The results of genetic screening were analyzed according to the symptoms and the length of QTc interval. Genetic screening was performed using dHPLC-DNA sequencing, HRM or NGS for at least KCNQ1 , KCNH2 and SCN5A . Results The population consisted in 456 probands affected by LQTS according to the Schwartz score (298 females, sex-ratio=1.9), mean age at diagnosis of 34±20 years. 214 patients (47%) were symptomatic: 54 patients (12%) experienced resuscitated SCD, 191 (42%) syncopes and 47 (10%) ventricular arrhythmias. Moreover, 73 patients (16%) had a history of familial SCD. An ICD was implanted in 62 of 456 patients (14%). Heart rate was 67±18 bpm, PR 151±51mm, QRS 87±17mm and QTc 486±55mm. Genetic screening was positive for 263 patients (58%): 122 mutations (27%) in KCNQ1 , 103 mutations (23%) in KCNH2 , 29 mutations (6%) in SCN5A and 10 mutations in minor genes of LQTS ( KCNE1, KCNE2, KCNJ2 and CACNA1C) . QTc duration was similar in asymptomatic patients with (483+/-45ms) or without mutation (QTc 476+/-49ms), NS. QTc duration was longer in symptomatic patients with (514+/-68ms) than without (470+/-47ms) mutations. Conclusion We identified a mutation in 58% of patients suspected for LQTS. The frequency of mutations are similar in all the different groups except for the symptomatic with QTc Table QTc QTc>480ms Number of patients Number of mutations % of mutated patients Number of patients Number of mutations % of mutated patients Asymptomatic 143 86 60% 99 69 70% Symptomatic 109 39 36% 105 69 66%