title: Arrhythmia phenotype during fetal life suggests long-QT syndrome genotype: risk stratification of perinatal long-QT syndrome.
abstract: BACKGROUND
  Fetal arrhythmias characteristic of long QT syndrome (LQTS) include torsades de pointes (TdP) and/or 2° atrioventricular block, but sinus bradycardia, defined as fetal heart rate<3% for gestational age, is most common. We hypothesized that prenatal rhythm phenotype might predict LQTS genotype and facilitate improved risk stratification and management.
  
  
  RESULTS
  Records of subjects exhibiting fetal LQTS arrhythmias were reviewed. Fetal echocardiograms, neonatal ECG, and genetic testing were evaluated. We studied 43 subjects exhibiting fetal LQTS arrhythmias: TdP±2° atrioventricular block (group 1, n=7), isolated 2° atrioventricular block (group 2, n=4), and sinus bradycardia (group 3, n=32). Mutations in known LQTS genes were found in 95% of subjects tested. SCN5A mutations occurred in 71% of group 1, whereas 91% of subjects with KCNQ1 mutations were in group 3. Small numbers of subjects with KCNH2 mutations (n=4) were scattered in all 3 groups. Age at presentation did not differ among groups, and most subjects (n=42) were live-born with gestational ages of 37.5±2.8 weeks (mean±SD). However, those with TdP were typically delivered earlier. Prenatal treatment in group 1 terminated (n=2) or improved (n=4) TdP. The neonatal heart rate-corrected QT interval (mean±SE) of group 1 (664.7±24.9) was longer than neonatal heart rate-corrected QT interval in both group 2 (491.2±27.6; P=0.004) and group 3 (483.1±13.7; P<0.001). Despite medical and pacemaker therapy, postnatal cardiac arrest (n=4) or sudden death (n=1) was common among subjects with fetal/neonatal TdP.
  
  
  CONCLUSIONS
  Rhythm phenotypes of fetal LQTS have genotype-suggestive features that, along with heart rate-corrected QT interval duration, may risk stratify perinatal management.
authors.affiliation: Department of Pediatrics, Rosalind Franklin School of Medicine and Science, North Chicago, IL.
authors.forename: Bettina F
authors.initials: BF
authors.lastname: Cuneo
authors.forename: Susan P
authors.initials: SP
authors.lastname: Etheridge
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Horigome
authors.forename: Denver
authors.initials: D
authors.lastname: Sallee
authors.forename: Anita
authors.initials: A
authors.lastname: Moon-Grady
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Weng
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ackerman
authors.forename: D Woodrow
authors.initials: DW
authors.lastname: Benson
mesh_terms: D054537:Atrioventricular Block / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D001919:Bradycardia / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D000072237:ERG1 Potassium Channel; D004452:Echocardiography; D004562:Electrocardiography; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D005838:Genotype; D006339:Heart Rate; D006801:Humans; D007231:Infant, Newborn; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D008133:Long QT Syndrome / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D009154:Mutation; D062554:NAV1.5 Voltage-Gated Sodium Channel / Q000235:genetics*; D010641:Phenotype; D011247:Pregnancy; D011256:Pregnancy Outcome; D011296:Prenatal Diagnosis; D018570:Risk Assessment
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D062554:NAV1.5 Voltage-Gated Sodium Channel; C568320:SCN5A protein, human
keywords: arrhythmias, cardiac; atrioventricular block; fetal; long-QT syndrome; sinus bradycardia torsade de pointes