title: Effective long-term control of cardiac events with beta-blockers in a family with a common LQT1 mutation.
abstract: 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.
authors.affiliation: Departments of Cardiology and Angiology,University of Münster, Albert-Schweitzer-Strasse 33, D-48149 Münster, Germany. hwede@uni-muenster.de
authors.forename: H
authors.initials: H
authors.lastname: Wedekind
authors.forename: M
authors.initials: M
authors.lastname: Schwarz
authors.forename: S
authors.initials: S
authors.lastname: Hauenschild
authors.forename: H
authors.initials: H
authors.lastname: Djonlagic
authors.forename: W
authors.initials: W
authors.lastname: Haverkamp
authors.forename: G
authors.initials: G
authors.lastname: Breithardt
authors.forename: T
authors.initials: T
authors.lastname: Wülfing
authors.forename: O
authors.initials: O
authors.lastname: Pongs
authors.forename: D
authors.initials: D
authors.lastname: Isbrandt
authors.forename: E
authors.initials: E
authors.lastname: Schulze-Bahr
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000818:Animals; D002318:Cardiovascular Diseases / Q000188:drug therapy / Q000517:prevention & control*; D016757:Death, Sudden, Cardiac; D004594:Electrophysiology; D005192:Family Health; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense / Q000502:physiology*; D009865:Oocytes; D010375:Pedigree; D010641:Phenotype; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics / Q000502:physiology; D029597:Romano-Ward Syndrome / Q000235:genetics*; D014981:Xenopus
chemical_list: D000319:Adrenergic beta-Antagonists; D051656:KCNQ Potassium Channels; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D024642:Potassium Channels, Voltage-Gated