Long QT syndrome in neonates: conduction disorders associated with HERG mutations and sinus bradycardia with KCNQ1 mutations.

Objectives: We hypothesized that neonatal long QT syndrome (LQTS) with 2:1 atrioventricular block (AVB) could be related to HERG mutations.

Background: Early onset of LQTS is rare but carries a high risk of life-threatening events such as ventricular arrhythmias and conduction disorders. There are no data on possible gene specificity.

Methods: We analyzed the characteristics and outcomes of 23 neonate probands from our LQTS population. Samples of DNA were available in 18 cases.

Results: Long QT syndrome was diagnosed because of corrected QT interval (QTc) prolongation (mean QTc of 558 +/- 62 ms) and neonatal bradycardia attributable to sinus bradycardia (n = 8) or 2:1 AVB (n = 15). Symptoms included syncope (n = 2), torsades de pointes (n = 7), and hemodynamic failure (n = 6). Three infants with 2:1 AVB died during the first month of life. During the neonatal period, all living patients received beta-blockers (BB) and 13 had a combination of BB and permanent cardiac pacing. Under treatment, patients remained asymptomatic, with a mean follow-up of seven years. Mutations were identified in HERG (n = 8) and KCNQ1 (n = 8), and one child had three mutations (HERG, KCNQ1, and SCN5A). Conduction disorders were associated with LQT2, whereas sinus bradycardia was associated with LQT1.

Conclusions: Two-to-one AVB seems preferentially associated with HERG mutations, either isolated or combined. Long QT syndrome with relative bradycardia attributable to 2:1 AVB has a poor prognosis during the first month of life. In contrast, sinus bradycardia seems to be associated with KCNQ1 mutations, with a good short-term prognosis under BB therapy.