Clinical characteristics and genetic background of congenital long-QT syndrome diagnosed in fetal, neonatal, and infantile life: a nationwide questionnaire survey in Japan.
BACKGROUND
Data on the clinical presentation and genotype-phenotype correlation of patients with congenital long-QT syndrome (LQTS) diagnosed at perinatal through infantile period are limited. A nationwide survey was conducted to characterize how LQTS detected during those periods is different from that in childhood or adolescence.


RESULTS
Using questionnaires, 58 cases were registered from 33 institutions. Diagnosis (or suspicion) of LQTS was made during fetal life (n=18), the neonatal period (n=31, 18 of them at 0 to 2 days of life), and beyond the neonatal period (n=9). Clinical presentation of LQTS included sinus bradycardia (n=37), ventricular tachycardia/torsades de pointes (n=27), atrioventricular block (n=23), family history of LQTS (n=21), sudden cardiac death/aborted cardiac arrest (n=14), convulsion (n=5), syncope (n=5), and others. Genetic testing was available in 41 (71%) cases, and the genotype was confirmed in 29 (71%) cases, consisting of LQT1 (n=11), LQT2 (n=11), LQT3 (n=6), and LQT8 (n=1). Ventricular tachycardia/torsades de pointes and atrioventricular block were almost exclusively observed in patients with LQT2, LQT3, and LQT8, as well as in those with no known mutation. In LQT1 patients, clues to diagnosis were mostly sinus bradycardia or family history of LQTS. Sudden cardiac death/aborted cardiac arrest (n=14) was noted in 4 cases with no known mutations as well as in 4 genotyped cases, although the remaining 6 did not undergo genotyping. Their subsequent clinical course after aborted cardiac arrest was favorable with administration of beta-blockers and mexiletine and with pacemaker implantation/implantable cardioverter-defibrillator.


CONCLUSIONS
Patients with LQTS who showed life-threatening arrhythmias at perinatal periods were mostly those with LQT2, LQT3, or no known mutations. Independent of the genotype, aggressive intervention resulted in effective suppression of arrhythmias, with only 7 deaths recorded.
Horigome
Hitoshi
H
Department of Child Health, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan. hhorigom@md.tsukuba.ac.jp
Nagashima
Masami
M
Sumitomo
Naokata
N
Yoshinaga
Masao
M
Ushinohama
Hiroya
H
Iwamoto
Mari
M
Shiono
Junko
J
Ichihashi
Koh
K
Hasegawa
Satoshi
S
Yoshikawa
Tadahiro
T
Matsunaga
Tamotsu
T
Goto
Hiroko
H
Waki
Kenji
K
Arima
Masaki
M
Takasugi
Hisashi
H
Tanaka
Yasuhiko
Y
Tauchi
Nobuo
N
Ikoma
Masanobu
M
Inamura
Noboru
N
Takahashi
Hideto
H
Shimizu
Wataru
W
Horie
Minoru
M
D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D003625:Data Collection; D016757:Death, Sudden, Cardiac / Q000209:etiology; D004562:Electrocardiography; D005260:Female; D005315:Fetal Diseases; D005838:Genotype; D006323:Heart Arrest / Q000209:etiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D008133:Long QT Syndrome / Q000151:congenital* / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy; D008297:Male; D009154:Mutation; D010138:Pacemaker, Artificial; D010641:Phenotype; D011296:Prenatal Diagnosis
D000889:Anti-Arrhythmia Agents