Published Online
on September 14, 2009

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Original Article

Low Incidence of Sudden Cardiac Death in a Swedish Y111C-LQT1 Population

Annika Winbo¹; Ulla-Britt Diamant; Eva–Lena Stattin; Steen M. Jensen and Annika Rydberg

Umeå University Hospital, Umeå, Sweden

^* Corresponding author; email: annika.winbo{at}pediatri.umu.se

Background—A 10% cumulative incidence and a 0.3%/yr incidence rate of sudden cardiac death below 40 years of age and without therapy have been reported in the type 1 long QT syndrome. The Y111C-KCNQ1 mutation causes a severe phenotype in vitro, suggesting a high-risk mutation. Focusing on life-threatening cardiac events, this study investigates the phenotype among Y111C-KCNQ1 mutation-carriers in the Swedish population.

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 of age experienced syncope (30%). One mutation-carrier had an aborted cardiac arrest (1.25%). No case of sudden cardiac death was reported during a mean non-medicated follow-up of 25±20 years. This corresponds to a low incidence rate of life-threatening cardiac events (0.05%/yr vs. 0.3%/yr, p=0.025). In 8 Y111C families connected by a common ancestor, the natural history of the mutation was assessed investigating the survival over the age of 40 for 107 non-medicated ascertained mutation-carriers (n=24) and family members (n=83) born between 1873 and 1968. In total, 4 deaths in individuals below the age of 40 were noted: one case of non-cardiac 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 the long QT syndrome.

Key Words: death, sudden (if surviving, use heart arrest) • genetics • ion channels • long-QT syndrome • survival