Genetic and phenotypic analysis of dilated cardiomyopathy with conduction system disease: Demand for strategies in the management of presymptomatic lamin A/C mutant carriers

Item Type:	Article
Title:	Genetic and phenotypic analysis of dilated cardiomyopathy with conduction system disease: Demand for strategies in the management of presymptomatic lamin A/C mutant carriers
Creators Name:	Perrot, A. and Sigusch, H.H. and Naegele, H. and Genschel, J. and Lehmkuhl, H. and Hetzer, R. and Geier, C. and Perez, L.V. and Reinhard, D. and Dietz, R. and Osterziel, K.J. and Schmidt, H.H.
Abstract:	BACKGROUND: One-third of cases of dilated cardiomyopathy (DCM) is of familial aetiology. Several genes have been reported to cause the autosomal dominant form of DCM. AIMS: To analyze the lamin A/C gene (LMNA) in 31 unrelated patients with DCM and conduction system disease (CSD). METHODS: Patients and family members underwent physical examination, ECG/Holter-ECG, echocardiography, and selective coronary angiography. Genetic analysis of all coding exons of LMNA was performed using PCR and sequencing. RESULTS: Three different LMNA mutations (Arg377His, c.1397delA, c.424_425ins21nt) were identified in three families with autosomal dominant disease comprised of 39 individuals. 21 individuals were mutation carriers, of whom 12 were symptomatic. We observed a progressive and age-dependent form of DCM with CSD and arrhythmias. First, the patients developed a moderate left ventricular dilatation without symptoms. Later, systolic function declined progressively and the patients became symptomatic resulting in a high mortality due to sudden death and heart failure. CONCLUSIONS: Genetic screening leads to the identification of symptomatic and asymptomatic mutant carriers. The latter at a young age should be regarded as 'presymptomatic' because of the age-dependent disease manifestation. New guidelines are required for the management of these individuals.
Keywords:	Lamin A/C, LMNA, Mutation, Familial Dilated Cardiomyopathy, DCM, Conduction System Disease
Source:	European Journal of Heart Failure
ISSN:	1388-9842
Publisher:	Elsevier
Volume:	8
Number:	5
Page Range:	484-493
Date:	August 2006
Additional Information:	The original publication is available at www.sciencedirect.com
Official Publication:	https://doi.org/10.1016/j.ejheart.2005.11.004
PubMed:	View item in PubMed

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