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. METHODS AND 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.

Effects of antenatal dexamethasone on antioxidant enzymes and nitric oxide synthase in the rat lung.

We investigated the effects of prenatal dexamethasone (DEX) administration on antioxidant enzymes (AOEs) and nitric oxide synthase (NOS) in fetal and neonatal rat lungs. DEX (1 mg/kg, s.c., for 2 days) or vehicle alone was administered to pregnant rats, and the lungs of fetuses on days 19 and 21 of gestation and of 1- and 3-day-old neonates were examined. We measured protein levels of the AOEs manganese superoxide dismutase and copper-zinc superoxide dismutase (Mn SOD and Cu-Zn SOD), glutathione peroxidase (GSH-Px), catalase (CAT), and inducible and endothelial nitric oxide synthase (i-NOS and e-NOS). Mn SOD, GSH-Px, and e-NOS expression gradually increased with increasing gestational and postnatal age in the lungs of the control groups. Cu-Zn SOD, CAT, and i-NOS expression did not change with increasing gestational and postnatal age in the lungs of the control groups. DEX administration had significant effects on i-NOS and e-NOS protein and mRNA expression. The increased Mn SOD, GSH-Px, and e-NOS expressions during the perinatal period suggests that antenatal developmental changes in AOEs in the lungs of premature fetuses could be reduced by reactive oxygen species-mediated injury at birth. Furthermore, antenatal glucocorticoid treatment may accelerate the development of lungs via the two types of NOS.