Low incidence of sudden cardiac death in a Swedish Y111C type 1 long-QT syndrome population.
Circ Cardiovasc Genet
; 2(6): 558-64, 2009 Dec.
Article
in En
| MEDLINE
| ID: mdl-20031635
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. METHODS ANDRESULTS:
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Death, Sudden, Cardiac
/
Mutation, Missense
/
Romano-Ward Syndrome
/
KCNQ1 Potassium Channel
Type of study:
Incidence_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adolescent
/
Adult
/
Aged
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
/
Middle aged
Country/Region as subject:
Europa
Language:
En
Journal:
Circ Cardiovasc Genet
Journal subject:
ANGIOLOGIA
/
CARDIOLOGIA
/
GENETICA MEDICA
Year:
2009
Document type:
Article
Affiliation country:
Sweden