Long QT syndrome in neonates: conduction disorders associated with HERG mutations and sinus bradycardia with KCNQ1 mutations.
OBJECTIVE
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.
Lupoglazoff
Jean-Marc
JM
Pediatric Cardiology, Necker-Enfants-Malades (AP/HP), Paris, France. jean=marc.lupoglazo@rdb.ap-hop-paris.fr
Denjoy
Isabelle
I
Villain
Elisabeth
E
Fressart
Véronique
V
Simon
Françoise
F
Bozio
André
A
Berthet
Myriam
M
Benammar
Nawal
N
Hainque
Bernard
B
Guicheney
Pascale
P
D001919:Bradycardia / Q000235:genetics*; D027682:Cation Transport Proteins / Q000235:genetics*; D051638:Ether-A-Go-Go Potassium Channels; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007231:Infant, Newborn; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008133:Long QT Syndrome / Q000235:genetics*; D008297:Male; D009154:Mutation; D015221:Potassium Channels / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated
D027682:Cation Transport Proteins; D051638:Ether-A-Go-Go Potassium Channels; C092509:KCNH6 protein, human; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated