title: Low incidence of sudden cardiac death in a Swedish Y111C type 1 long-QT syndrome population.
abstract: BACKGROUND
  A 10% cumulative incidence and a 0.3% per year incidence rate of sudden cardiac death in patients younger than 40 years and without therapy have been reported in type 1 long-QT syndrome. The Y111C-KCNQ1 mutation causes a severe phenotype in vitro, suggesting a high-risk mutation. This study investigated the phenotype among Y111C-KCNQ1 mutation carriers in the Swedish population with a focus on life-threatening cardiac events.
  
  
  RESULTS
  We identified 80 mutation carriers in 15 index families, segregating the Y111C-KCNQ1 mutation during a national inventory of mutations causing the long-QT syndrome. Twenty-four mutation carriers <40 years experienced syncope (30%). One mutation carrier had an aborted cardiac arrest (1.25%). No case of sudden cardiac death was reported during a mean nonmedicated follow-up of 25+/-20 years. This corresponds to a low incidence rate of life-threatening cardiac events (0.05%/year versus 0.3%/year, P=0.025). In 8 Y111C families connected by a common ancestor, the natural history of the mutation was assessed by investigating the survival over the age of 40 years for 107 nonmedicated ascertained mutation carriers (n=24) and family members (n=83) born between 1873 and 1968. In total, 4 deaths in individuals younger than 40 years were noted: 1 case of noncardiac death and 3 infant deaths between 1873 and 1915.
  
  
  CONCLUSIONS
  The dominant-negative Y111C-KCNQ1 mutation, associated with a severe phenotype in vitro, presents with a low incidence of life-threatening cardiac events in a Swedish population. This finding of discrepancy emphasizes the importance of clinical observations in the risk stratification of long-QT syndrome.
authors.affiliation: Division of Pediatrics, Department of Clinical Sciences, Cardiology Heart Centre, Umeå University Hospital, Umeå, Sweden. annika.winbo@pediatri.umu.se
authors.forename: Annika
authors.initials: A
authors.lastname: Winbo
authors.forename: Ulla-Britt
authors.initials: UB
authors.lastname: Diamant
authors.forename: Eva-Lena
authors.initials: EL
authors.lastname: Stattin
authors.forename: Steen M
authors.initials: SM
authors.lastname: Jensen
authors.forename: Annika
authors.initials: A
authors.lastname: Rydberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D016757:Death, Sudden, Cardiac / Q000453:epidemiology*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D051657:KCNQ1 Potassium Channel / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree; D029597:Romano-Ward Syndrome / Q000453:epidemiology* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D013548:Sweden / Q000453:epidemiology; D055815:Young Adult
chemical_list: D051657:KCNQ1 Potassium Channel