RESUMO
BACKGROUND: Inherited arrhythmogenic disorders are a group of genetically determined diseases characterised by ventricular tachyarrhythmias sometimes leading to sudden death. The molecular bases of these disorders are mutations in genes coding for various cardiac ion channels. The most common cardiac ion channel disease is the long QT syndrome. This syndrome is rare, but probably more common in Norway than previously expected. We have recently started genetic testing for cardiac ion channel disorders at Rikshospitalet University Hospital in Oslo. This review describes the current understanding of the etiology, prognosis and management of cardiac ion channel disorders, based on literature and our own clinical experience. INTERPRETATION: Cardiac ion channel disorders may lead to sudden cardiac death. Prophylactic and life-saving therapies are available for many of these disorders. Therapy and risk stratification depend on the clinical presentation, the ECG pattern, and which gene is mutated. Genetic testing offers the opportunity to exclude individual family members as mutation carriers.
Assuntos
Arritmias Cardíacas , Síndrome do QT Longo , Adulto , Arritmias Cardíacas/congênito , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/tratamento farmacológico , Arritmias Cardíacas/genética , Bloqueio de Ramo/congênito , Bloqueio de Ramo/diagnóstico , Bloqueio de Ramo/tratamento farmacológico , Bloqueio de Ramo/genética , Criança , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Predisposição Genética para Doença , Testes Genéticos , Humanos , Lactente , Síndrome do QT Longo/congênito , Síndrome do QT Longo/diagnóstico , Síndrome do QT Longo/tratamento farmacológico , Síndrome do QT Longo/genética , Mutação , Fenótipo , Canais de Potássio/genética , Canais de Potássio/fisiologia , Prognóstico , Fatores de Risco , Canais de Sódio/genética , Canais de Sódio/fisiologia , SíndromeRESUMO
BACKGROUND: Long QT syndrome is characterised by inherited long QT interval on the ECG and increased risk for syncope and sudden death caused by arrhythmias. For Romano-Ward syndrome and Jervell and Lange-Nielsen syndrome DNA based diagnostics are available. MATERIALS AND METHODS: This paper is a summary of our experience with DNA-based diagnostics of LQTS since the autumn of 2003. The diagnostic analyses are performed by sequencing the exons of five genes, KCNQ1, HERG, SCN5A, minK and MiRP1. RESULTS AND INTERPRETATIONS: As of mid-January 2005, 56 probands with long QT syndrome have been referred for genetic testing. We have identified an underlying mutation in 64% of the patients. Mutations in the KCNQ1 gene are most frequent in Norwegian long QT syndrome patients, as 61% of the patients have their mutation in this gene. The detection of a mutation in the probands has led to genetic testing of 215 relatives; 99 out of these are heterozygous for the mutation present in the family. Heterozygous patients have been referred to a cardiologist. Of the 43 that have been referred to follow up at the department of cardiology at Rikshospitalet, 35 have started treatment with beta blockers to reduce the risk of arrhythmias. Thus, DNA-based diagnostics has clinical significance leading to prophylactic treatment of long QT syndrome patients. Compared to evaluation of ECG, which is negative in 30% of mutation carriers, the sensitivity of DNA-based diagnostics of relatives of probands with a known mutation, is close to 1.