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CLINICAL RESEARCH: HEART RHYTHM DISORDER

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, Groningen, the Netherlands
University Hospital, Department of Cardiology, Groningen, the Netherlands
Clinical Genetics, Groningen, the Netherlands
Experimental and Molecular Cardiology Group, Academic Medical Center, Amsterdam, the Netherlands
^|| 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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