Winbo Annika, Diamant Ulla-Britt, Stattin Eva-Lena, Jensen Steen M, Rydberg Annika
Division of Pediatrics, Department of Clinical Sciences, Cardiology Heart Centre, Umeå University Hospital, Umeå, Sweden.
Circ Cardiovasc Genet. 2009 Dec;2(6):558-64. doi: 10.1161/CIRCGENETICS.108.825547. Epub 2009 Sep 14.
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.
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.
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.
据报道，1型长QT综合征患者中，年龄小于40岁且未经治疗者心脏性猝死的累积发生率为10%，年发生率为0.3%。Y111C-KCNQ1突变在体外可导致严重表型，提示其为高风险突变。本研究调查了瑞典人群中Y111C-KCNQ1突变携带者的表型，重点关注危及生命的心脏事件。
在全国范围内对导致长QT综合征的突变进行排查期间，我们在15个索引家族中鉴定出80名Y111C-KCNQ1突变携带者。24名年龄小于40岁的突变携带者发生了晕厥（30%）。1名突变携带者发生了心脏骤停但复苏成功（1.25%）。在平均25±20年的未用药随访期间，未报告心脏性猝死病例。这对应着危及生命的心脏事件的低发生率（0.05%/年 vs 0.3%/年，P=0.025）。在8个由共同祖先相连的Y111C家族中，通过调查1873年至1968年间出生的107名经确定的未用药突变携带者（n=24）和家庭成员（n=83）40岁以上的生存情况，评估了该突变的自然史。总共记录到4例40岁以下个体死亡：1例非心脏性死亡和1873年至1915年间的3例婴儿死亡。
在体外与严重表型相关的显性负性Y111C-KCNQ1突变，在瑞典人群中危及生命的心脏事件发生率较低。这一差异的发现强调了临床观察在长QT综合征风险分层中的重要性。
