Low incidence of sudden cardiac death in a Swedish Y111C type 1 long-QT syndrome population
2009 (English)In: Circulation: Cardiovascular Genetics, ISSN 1942-325X, Vol. 2, no 6, 558-564 p.Article in journal (Refereed) Published
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.
Methods and 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.
Place, publisher, year, edition, pages
Philadelphia, PA: Lippincott Williams & Wilkins , 2009. Vol. 2, no 6, 558-564 p.
death, sudden, genetics, ion channels, long-QT syndrome, survival
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:umu:diva-32464DOI: 10.1161/CIRCGENETICS.108.825547PubMedID: 20031635OAI: oai:DiVA.org:umu-32464DiVA: diva2:303286