title: Meta-analysis of clinical characteristics of 299 carriers of LMNA gene mutations: do lamin A/C mutations portend a high risk of sudden death?
abstract: This study evaluated common clinical characteristics of patients with lamin A/C gene mutations that cause either isolated dilated cardiomyopathy or dilated cardiomyopathy in association with skeletal muscular dystrophy. We pooled clinical data of all published carriers of lamin A/C gene mutations as cause of skeletal and/or cardiac muscle disease and reviewed ECG findings. Cardiac dysrhythmias were reported in 92% of patients after the age of 30 years; heart failure was reported in 64% after the age of 50. Sudden death was the most frequently reported mode of death (46%) in both the cardiac and the neuromuscular phenotype. Carriers of lamin A/C gene mutations often received a pacemaker (28%). However, this intervention did not alter the rate of sudden death. Review of the ECG findings typically showed a low amplitude P wave and prolongation of the PR interval with a narrow QRS complex. This meta-analysis suggests that cardiomyopathy due to lamin A/C gene mutations portends a high risk of sudden death, and that this risk does not differ between subjects with predominantly cardiac or neuromuscular disease. This implies then that all carriers of a lamin A/C gene mutation need to be carefully screened with particular emphasis also on tachyarrhythmias. Prospective studies are needed to evaluate risk stratification and proper treatment strategies.
authors.affiliation: Department of Cardiology , University Hospital Maastricht, and Cardiovascular Research Institute Maastricht, P. Debyelaan 25, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands.
authors.forename: Jop H
authors.initials: JH
authors.lastname: van Berlo
authors.forename: Willem G
authors.initials: WG
authors.lastname: de Voogt
authors.forename: Anneke J
authors.initials: AJ
authors.lastname: van der Kooi
authors.forename: J Peter
authors.initials: JP
authors.lastname: van Tintelen
authors.forename: Gisèle
authors.initials: G
authors.lastname: Bonne
authors.forename: Rabah Ben
authors.initials: RB
authors.lastname: Yaou
authors.forename: Denis
authors.initials: D
authors.lastname: Duboc
authors.forename: Tom
authors.initials: T
authors.lastname: Rossenbacker
authors.forename: Hein
authors.initials: H
authors.lastname: Heidbüchel
authors.forename: Marianne
authors.initials: M
authors.lastname: de Visser
authors.forename: Harry J G M
authors.initials: HJ
authors.lastname: Crijns
authors.forename: Yigal M
authors.initials: YM
authors.lastname: Pinto
mesh_terms: D001145:Arrhythmias, Cardiac / Q000235:genetics / Q000378:metabolism; D003645:Death, Sudden; D020022:Genetic Predisposition to Disease; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D034904:Lamin Type A; D034882:Lamins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D010138:Pacemaker, Artificial
chemical_list: C494847:LMNA protein, human; D034904:Lamin Type A; D034882:Lamins