The congenital long QT syndrome (LQTS) is characterized by a prolonged QT 
interval on the surface electrocardiogram and an increased risk of recurrent 
syncope and sudden cardiac death. Mutations in seven genes have been identified 
as the molecular basis of LQTS. beta-blockers are the treatment of choice to 
reduce cardiac symptoms. However, long-term follow-up of genotyped families with 
LQTS has been rarely reported. We have clinically followed a four-generation 
family with LQTS being treated with beta-blocker therapy over a period of 23 
years. Seven family members were carriers of two amino acid alterations in cis 
(V254M-V417M) in the cardiac potassium channel gene KCNQ1. Voltage-clamp 
recordings of mutant KCNQ1 protein in Xenopus oocytes showed that only the V254M 
mutation reduced the IKs current and that the effect of the V417M variant was 
negligible. The family exhibited the complete clinical spectrum of the disease, 
from asymptomatic patients to victims of sudden death before beta-blocker 
therapy. There was no significant reduction in QTc (556 +/- 40 ms(1/2) before 
therapy, 494 +/- 20 ms(1/2) during 17 years of treatment; n = 5 individuals). Of 
nine family members, one female died suddenly before treatment, three females of 
the second generation were asymptomatic, and four individuals of the third and 
fourth generation were symptomatic. All mutation carriers were treated with 
beta-blockers and remained asymptomatic for a follow-up up to 23 years. 
Long-term follow-up of a LQT1 family with a common mutation (V254M) being on 
beta-blocker therapy was effective and safe. This study underscores the 
importance of long-term follow-up in families with specific LQT mutations to 
provide valuable information for clinicians for an appropriate antiarrhythmic 
treatment.