title: Combined assessment of sex- and mutation-specific information for risk stratification in type 1 long QT syndrome.
abstract: BACKGROUND
  Men and women with type 1 long QT syndrome (LQT1) exhibit time-dependent differences in the risk for cardiac events.
  
  
  OBJECTIVE
  We hypothesized that sex-specific risk for LQT1 is related to the location and function of the disease-causing mutation in the KCNQ1 gene.
  
  
  METHODS
  The risk for life-threatening cardiac events (comprising aborted cardiac arrest [ACA] or sudden cardiac death [SCD]) from birth through age 40 years was assessed among 1051 individuals with LQT1 (450 men and 601 women) by the location and function of the LQT1-causing mutation (prespecified as mutations in the intracellular domains linking the membrane-spanning segments [ie, S2-S3 and S4-S5 cytoplasmic loops] involved in adrenergic channel regulation vs other mutations).
  
  
  RESULTS
  Multivariate analysis showed that during childhood (age group: 0-13 years) men had >2-fold (P < .003) increased risk for ACA/SCD than did women, whereas after the onset of adolescence the risk for ACA/SCD was similar between men and women (hazard ratio = 0.89 [P = .64]). The presence of cytoplasmic-loop mutations was associated with a 2.7-fold (P < .001) increased risk for ACA/SCD among women, but it did not affect the risk among men (hazard ratio 1.37; P = .26). Time-dependent syncope was associated with a more pronounced risk-increase among men than among women (hazard ratio 4.73 [P < .001] and 2.43 [P = .02], respectively), whereas a prolonged corrected QT interval (≥ 500 ms) was associated with a higher risk among women than among men.
  
  
  CONCLUSIONS
  Our findings suggest that the combined assessment of clinical and mutation location/functional data can be used to identify sex-specific risk factors for life-threatening events for patients with LQT1.
authors.affiliation: Cardiology Division, University of Rochester Medical Center, Rochester, NY 14642, USA.
authors.forename: Jason
authors.initials: J
authors.lastname: Costa
authors.forename: Coeli M
authors.initials: CM
authors.lastname: Lopes
authors.forename: Alon
authors.initials: A
authors.lastname: Barsheshet
authors.forename: Arthur J
authors.initials: AJ
authors.lastname: Moss
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Migdalovich
authors.forename: Gregory
authors.initials: G
authors.lastname: Ouellet
authors.forename: Scott
authors.initials: S
authors.lastname: McNitt
authors.forename: Slava
authors.initials: S
authors.lastname: Polonsky
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Robinson
authors.forename: Wojciech
authors.initials: W
authors.lastname: Zareba
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Ackerman
authors.forename: Jesaia
authors.initials: J
authors.lastname: Benhorin
authors.forename: Elizabeth S
authors.initials: ES
authors.lastname: Kaufman
authors.forename: Pyotr G
authors.initials: PG
authors.lastname: Platonov
authors.forename: Wataru
authors.initials: W
authors.lastname: Shimizu
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Towbin
authors.forename: G Michael
authors.initials: GM
authors.lastname: Vincent
authors.forename: Arthur A M
authors.initials: AA
authors.lastname: Wilde
authors.forename: Ilan
authors.initials: I
authors.lastname: Goldenberg
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004247:DNA / Q000235:genetics*; D016757:Death, Sudden, Cardiac / Q000453:epidemiology* / Q000209:etiology; D004562:Electrocardiography; D005260:Female; D005838:Genotype; D014943:Global Health; D006801:Humans; D015994:Incidence; D007223:Infant; D007231:Infant, Newborn; D051657:KCNQ1 Potassium Channel / Q000235:genetics* / Q000378:metabolism; D008297:Male; D009154:Mutation; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D029597:Romano-Ward Syndrome / Q000150:complications / Q000453:epidemiology* / Q000235:genetics; D017678:Sex Distribution; D012737:Sex Factors; D015996:Survival Rate / Q000639:trends; D055815:Young Adult
chemical_list: D051657:KCNQ1 Potassium Channel; D004247:DNA