CLINICAL RESEARCH: ELECTROPHYSIOLOGY
Long QT syndrome in neonates
Conduction disorders associated with HERG mutations and sinus bradycardia with KCNQ1 mutations
Jean-Marc Lupoglazoff, MD, PhD* ,*,
Isabelle Denjoy, MD* ,
Elisabeth Villain, MD ,
Véronique Fressart, MD||,
Françoise Simon||,
André Bozio, MD¶,
Myriam Berthet,
Nawal Benammar,
Bernard Hainque, PhD|| and
Pascale Guicheney, PhD
* Pediatric Cardiology, Robert Debré Hospital (AP/HP), Paris, France
INSERM U582, Institut de Myologie Pitié-Salpêtrière Hospital (AP/HP), Paris, France
Cardiology, Lariboisière Hospital (AP/HP), Paris, France
Pediatric Cardiology, Necker-Enfants-Malades (AP/HP), Paris, France
|| Biochemistry and Molecular Biology, Pitié-Salpêtrière Hospital (AP/HP), Paris, France
¶ Pediatric Cardiology, Lyon, France
Manuscript received May 27, 2003;
revised manuscript received September 12, 2003,
accepted September 15, 2003.
* Reprint requests and correspondence: Dr. Jean-Marc Lupoglazoff, Cardiologie, Hôpital Robert Debré-48, Boulevard Sérurier, 75019 Paris, France.
jean-marc.lupoglazof{at}rdb.ap-hop-paris.fr
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.
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Abbreviations and Acronyms
| | AV | = atrioventricular | | AVB | = atrioventricular block | | BB | = beta-blocker/blocking | | QTc | = corrected QT interval | | ECG | = electrocardiogram | | LQTS | = long QT syndrome |
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