Meta-analysis of clinical characteristics of 299 carriers of LMNA gene mutations: do lamin A/C mutations portend a high risk of sudden death?
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.
van Berlo
Jop H
JH
Department of Cardiology , University Hospital Maastricht, and Cardiovascular Research Institute Maastricht, P. Debyelaan 25, P.O. Box 5800, 6202 AZ, Maastricht, The Netherlands.
de Voogt
Willem G
WG
van der Kooi
Anneke J
AJ
van Tintelen
J Peter
JP
Bonne
Gisèle
G
Yaou
Rabah Ben
RB
Duboc
Denis
D
Rossenbacker
Tom
T
Heidbüchel
Hein
H
de Visser
Marianne
M
Crijns
Harry J G M
HJ
Pinto
Yigal M
YM
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
C494847:LMNA protein, human; D034904:Lamin Type A; D034882:Lamins