Developmental aspects of long QT syndrome type 3 and Brugada syndrome on the basis of a single SCN5A mutation in childhood

OBJECTIVES: The aim was to investigate at what age electrocardiographic characteristics of long QT syndrome type 3 (LQT3) and Brugada syndrome (BS), based on a single SNC5A mutation, appear.

BACKGROUND: The QT interval (QT) in LQT3 is prolonged during bradycardia. It is not clear yet if this is obvious in young children with a relative fast heart rate (HR).

METHODS: Thirty-six children with an SNC5A gene mutation (1795insD) and 46 non-carrier siblings were investigated. In different age groups, HR, QT, QTc, and ST-segment elevation on a 12-lead electrocardiogram (ECG), and HR, QT, QTc, and DeltaQT after the longest pause in a Holter (recording) were evaluated.

RESULTS: In all age groups, HR at rest tended to be lower in carriers than in non-carriers, and QT was longer in carriers than in non-carriers. The Brugada phenotype was found >5 years. Gender specific differences were not identified. The QT at lower HR and DeltaQT were longer in carriers than in non-carriers. A QTc of > or =0.44 s at the lowest HR (sensitivity 100%; specificity 88.4%) and DeltaQT > or =60 ms (sensitivity 100%; specificity 82.6%) were good predictors for having LQT3.

CONCLUSIONS: We conclude that electrocardiographic characteristics of LQT3 and BS show age-dependent penetrance. A QT prolongation and conduction disease were present from birth onwards, whereas ST-segment elevation only developed >5 years. Good tools for clinical diagnosis of LQT3 in this family are QTc at the lowest HR and DeltaQT after a pause in a Holter, even at very young age.