The Y111C-KCNQ1 mutation in a Swedish population was associated with a low incidence rate of life-threatening cardiac events compared to previously reported rates (0.05%/year vs 0.3%/year, P=0.025).
Observational (n=80)
Yes
The Y111C-KCNQ1 mutation, despite causing a severe phenotype in vitro, is associated with a low incidence of life-threatening cardiac events in vivo, highlighting the importance of clinical observation in long-QT syndrome risk stratification.
Absolute Event Rate: 0.05% vs 0.3%
p-value: p=0.025
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.
Winbo et al. (Tue,) conducted a observational in Y111C Type 1 Long-QT syndrome (n=80). Y111C-KCNQ1 mutation vs. Reported incidence in type 1 long-QT syndrome was evaluated on Life-threatening cardiac events (p=0.025). The Y111C-KCNQ1 mutation in a Swedish population was associated with a low incidence rate of life-threatening cardiac events compared to previously reported rates (0.05%/year vs 0.3%/year, P=0.025).