RESUMO
BACKGROUND: Fatal ventricular arrhythmias in the early period of life have been associated with cardiac channelopathies for decades, and postmortem analyses in SIDS victims have provided evidence of this association. However, the prevalence and functional properties of cardiac ion channel mutations in infantile fatal arrhythmia cases are not clear. METHODS AND RESULTS: Seven infants with potentially lethal arrhythmias at age < 1 year (5 males, age of onset 44.1 ± 72.1 days) were genetically analyzed for KCNQ1, KCNH2, KCNE1-5, KCNJ2, SCN5A, GJA5, and CALM1 by using denaturing high-performance liquid chromatography and direct sequencing. Whole-cell currents of wildtype and mutant channels were recorded and analyzed in Chinese hamster ovary cells transfected with SCN5A and KCNH2 cDNA. In 5 of 7 patients, we identified 4 mutations (p.N1774D, p.T290fsX53, p.F1486del and p.N406K) in SCN5A, and 1 mutation (p.G628D) in KCNH2. N1774D, F1486del, and N406K in SCN5A displayed tetrodotoxin-sensitive persistent late Na(+) currents. By contrast, SCN5A-T290fsX53 was nonfunctional. KCNH2-G628D exhibited loss of channel function. CONCLUSION: Genetic screening of 7 patients was used to demonstrate the high prevalence of cardiac channelopathies. Functional assays revealed both gain and loss of channel function in SCN5A mutations, as well as loss of function associated with the KCNH2 mutation.
Assuntos
Canalopatias/diagnóstico , Canalopatias/genética , Canais de Potássio Éter-A-Go-Go/genética , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/genética , Animais , Arritmias Cardíacas/complicações , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/genética , Síndrome de Brugada , Doença do Sistema de Condução Cardíaco , Canalopatias/complicações , Cricetinae , Canal de Potássio ERG1 , Evolução Fatal , Feminino , Sistema de Condução Cardíaco/anormalidades , Humanos , Lactente , Recém-Nascido , Masculino , Mutação/genética , Linhagem , Taquicardia Ventricular/complicaçõesRESUMO
We describe a case of Churg-Strauss syndrome (CSS) presenting with a massive pericardial effusion without overt myocardial dysfunction. A 60-year-old man was referred to our hospital because of exertional dyspnea and fever. Initial chest multidetector-row computed tomography showed a massive pericardial effusion. The presence of eosinophilia, infiltrates of both lungs, pathological evidence of necrotizing vasculitis associated with eosinophilic infiltration, and history of asthma fulfilled the criteria of CSS. Massive pericardial effusion can be the first manifestation of cardiac involvement in CSS.