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

J Am Coll Cardiol. 2005 Jul 19;46(2):331-7. doi: 10.1016/j.jacc.2005.03.066.

Abstract

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.

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Bundle-Branch Block / genetics*
  • Child
  • Child, Preschool
  • Death, Sudden, Cardiac*
  • Electrocardiography
  • Electrocardiography, Ambulatory
  • Exercise Test
  • Female
  • Heart Rate
  • Heterozygote
  • Humans
  • Infant
  • Long QT Syndrome / genetics*
  • Male
  • Mutation*
  • NAV1.5 Voltage-Gated Sodium Channel
  • Pedigree
  • Phenotype
  • Risk
  • Sensitivity and Specificity
  • Sodium Channels / genetics*

Substances

  • NAV1.5 Voltage-Gated Sodium Channel
  • SCN5A protein, human
  • Sodium Channels