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High Incidence of Sudden Death with Conduction System and Myocardial Disease Due to Lamins A and C Gene Mutation
Author(s) -
BÉCANE HENRIMARC,
BONNE GISÈLE,
VARNOUS SHAIDA,
MUCHIR ANTOINE,
ORTEGA VÉRONIQUE,
HAMMOUDA EL HADI,
URTIZBEREA JANDONI,
LAVERGNE THOMAS,
FARDEAU MICHEL,
EYMARD BRUNO,
WEBER SIMON,
SCHWARTZ KETTY,
DUBOC DENIS
Publication year - 2000
Publication title -
pacing and clinical electrophysiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.686
H-Index - 101
eISSN - 1540-8159
pISSN - 0147-8389
DOI - 10.1046/j.1460-9592.2000.01661.x
Subject(s) - lmna , medicine , lamin , sudden death , cardiology , sudden cardiac death , cardiomyopathy , dilated cardiomyopathy , hypertrophic cardiomyopathy , sick sinus syndrome , gene mutation , heart failure , mutation , genetics , gene , nucleus , psychiatry , biology
BÉCANE, H.–M., et al. : High Incidence of Sudden Death with Conduction System and Myocardial Disease Due to Lamins A and C Gene Mutation. We studied 54 living relatives from a large French kindred, among which 17 members presented with a cardiomyopathy transmitted on an autosomal dominant mode. Five of these individuals had clinical manifestations of muscle disease phenotypically consistent with Emery‐Dreifuss muscular dystrophy. Genetic analysis of this kindred had demonstrated a nonsense mutation in the LMNA gene located on chromosome 1q11–q23. This gene encodes lamins A and C, proteins of the nuclear lamina located on the inner face of the nuclear envelope. We retrospectively determined the cause of death of 15 deceased family members, 8 of whom had died suddenly, 2 as a first and single manifestation of the disease. The six other cases had histories of arrhythmias and left ventricular dysfunction before dying suddenly, and three of them died despite the prior implantation of a permanent pacemaker. The mean age of onset of cardiac symptoms among affected living family members was 33 years (range 15–47 years), and the first symptoms were due to marked atrioventricular conduction defects or sinus dysfunction, requiring the implantation of permanent pacemakers in seven cases. Myocardial dysfunction accompanied by ventricular arrhythmias developed rapidly in the course of the disease and resulted in severe dilated cardiomyopathy requiring cardiac transplantation in three cases. In conclusion, in patients presenting a life‐threatening familial or sporadic cardiac restricted phenotype similar to that described here, mutations in the lamins A and C gene should be looked for. In the genotypically affected individuals, cardiological and electrophysiological follow‐up should be performed to prevent sudden death that could occur rapidly in the evolution of such disease.