Asunto(s)
Antipsicóticos/efectos adversos , Bradicardia/inducido químicamente , Trastornos Psicóticos/tratamiento farmacológico , Risperidona/efectos adversos , Antipsicóticos/uso terapéutico , Bradicardia/diagnóstico , Relación Dosis-Respuesta a Droga , Electrocardiografía Ambulatoria , Humanos , Masculino , Persona de Mediana Edad , Risperidona/uso terapéuticoRESUMEN
BACKGROUND: Mutations in several ion channel genes have been reported to cause rare cases of familial atrial fibrillation (AF). OBJECTIVE: The purpose of this study was to determine the genetic basis for AF in a family with autosomal dominant AF. METHODS: Family members were evaluated by 12-lead ECG, echocardiogram, signal-averaged P-wave analysis, and laboratory studies. Fourteen family members in AF-324 were studied. Six individuals had AF, with a mean age at onset of 32 years (range 16-59 years). RESULTS: Compared with unaffected family members, those with AF had a longer mean QRS duration (100 vs 86 ms, P = .015) but no difference in the corrected QT interval (423 +/- 15 ms vs 421 +/- 21 ms). The known loci for AF and other cardiovascular diseases were evaluated. Evidence of linkage was obtained with marker D11S4088 located within KCNQ1, and a highly conserved serine in the third transmembrane region was found to be mutated to a proline (S209P). Compared to the wild-type channel, the S209P mutant activates more rapidly, deactivates more slowly, and has a hyperpolarizing shift in the voltage activation curve. A fraction of the mutant channels are constitutively open at all voltages, resulting in a net increase in I(Ks) current. CONCLUSION: We identified a family with lone AF due to a mutation in the highly conserved S3 domain of KCNQ1, a region of the channel not previously implicated in the pathogenesis of AF.
Asunto(s)
Fibrilación Atrial/genética , Canal de Potasio KCNQ1/genética , Adolescente , Adulto , Anciano , Electrocardiografía , Electrofisiología , Femenino , Humanos , Canales Iónicos/genética , Masculino , Persona de Mediana Edad , Mutación , Linaje , Factores de Riesgo , Volumen Sistólico , Secuencias Repetidas en Tándem , Adulto JovenRESUMEN
Sarcoid granulomas usually involve the myocardium with rare focal extensions into the pericardium and endocardium with resultant conduction defects, ventricular arrhythmias, and ventricular systolic and diastolic dysfunction. Primary involvement of valvular leaflets resulting in valvular regurgitation or stenosis is not known. We present a case of a wastewater consultant who developed tricuspid regurgitation and symptomatic atrioventricular block secondary to infiltration of tricuspid leaflets and conduction system from sarcoid granulomas. The patient later developed severe dilated cardiomyopathy as a result of extensive cardiac sarcoidosis necessitating cardiac transplantation. Valvular regurgitation should be included as one of the presenting manifestations of cardiac sarcoidosis.