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ARTICLE

Developmental Aspects of Long QT Syndrome Type 3 and Brugada Syndrome on the Basis of a Single SCN5A Mutation in Childhood

Gertie C.M. Beaufort-Krol, MD, PhD^_*, Maarten P. van den Berg, MD, PhD, Arthur A.M. Wilde, MD, PhD, J. Peter van Tintelen, MD, Jan Willem Viersma, MD, PhD, Connie R. Bezzina, PhD^,|| and Margreet Th.E. Bink-Boelkens, MD, PhD^_*,_*

^_* Beatrix Children's Hospital, Department of Pediatric Cardiology
University Hospital, Department of Cardiology
Clinical Genetics, Groningen, the Netherlands
Experimental and Molecular Cardiology Group
^|| Department of Clinical Genetics, Academic Medical Center, Amsterdam, the Netherlands

Manuscript received October 15, 2004; revised manuscript received March 22, 2005, accepted March 29, 2005.

^_* Reprint requests and correspondence: Dr. Margreet Th.E. Bink-Boelkens, Beatrix Children's Hospital, Department of Pediatric Cardiology, Hanzeplein 1, P.O. Box 30001, 9700 RB Groningen, the Netherlands (Email: m.t.e.bink{at}bkk.umcg.nl).

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, QT_c, and ST-segment elevation on a 12-lead electrocardiogram (ECG), and HR, QT, QT_c, and QT 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 QT were longer in carriers than in non-carriers. A QT_c of 0.44 s at the lowest HR (sensitivity 100%; specificity 88.4%) and QT 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 QT_c at the lowest HR and QT after a pause in a Holter, even at very young age.

Abbreviations and Acronyms   AP = action potential   BS = Brugada syndrome   ECG = electrocardiogram   HR = heart rate   Ito = transient outward current   LQT3 = long QT syndrome type 3   SAECG = signal-averaged electrocardiogram

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