Case report A mutation in the X-linked Emery±Dreifuss muscular dystrophy gene in a patient affected with conduction cardiomyopathy Stanislav Vohanka a , Michal Vytopil a , Josef Bednarik a , Zdenek Lukas b , Zdenek Kadanka a , Jiri Schildberger c , Roberta Ricotti d , Silvia Bione d , Daniela Toniolo d, * a Department of Neurology, University Hospital Brno, Jihlavska  20, 63900 Brno, Czech Republic b Second Department of Pathology, Medical Faculty of the Masaryk University, University Hospital Brno - Childrens Hospital, Cernopolni 9, 66263 Brno, Czech Republic c Department of Cardiology, University Hospital Brno, Jihlavska  20, 63900 Brno, Czech Republic d Institute of Genetics, Biochemistry and Evolution, CNR, Via Abbiategrasso 207, 27100 Pavia, Italy Received 9 May 2000; received in revised form 27 July 2000; accepted 22 September 2000 Abstract A screening for mutation in the X-linked Emery±Dreifuss muscular dystrophy (X-EMD) gene was performed among patients affected with severe heart rhythm defects and/or dilated cardiomyopathy. Patients were selected from the database of the Department of Cardiology of the University Hospital Brno. One patient presented a mutation in the X-EMD gene and no emerin in his skeletal muscle. The patient had a severe cardiac disease but a very mild muscle disorder that had not been diagnosed until the mutations was found. This case shows that mutations in X-EMD gene, as it was shown for autosomal-dominant EMD, can cause a predominant cardiac phenotype. q 2001 Elsevier Science B.V. All rights reserved. Keywords: Emery±Dreifuss muscular dystrophy; Mutations; Conduction cardiomyopathy 1. Introduction The Emery±Dreifuss muscular dystrophy (EMD) is a disorder characterized by the triad of early contractures of the elbows, Achilles tendons and postcervical muscles, slowly progressive muscle wasting and weakness with humeroperoneal distribution in the early stages of the disease and cardiomyopathy [1,2]. Cardiomyopathy usually presents as dysarrhytmia and conduction defects, complete heart block being the most dangerous consequence [1,2]. Early diagnosis is essential because of the potentially fatal arrhytmias which are responsible for sudden cardiac death. Family studies have shown that EMD can be inherited as X-linked, autosomal-dominant (AD) or autosomal-recessive (AR) [2,3]. Clinically the different genetic forms are very similar. The genes responsible for EMD were identi®ed [4±6]. The X-EMD gene encodes a 254 amino acids, highly phos- phorylated protein, emerin, a member of the nuclear lamina- associated protein family [4]. The gene for AD-EMD and AR-EMD is the lamin A/C gene (LMNA), encoding two lamins, lamin A and C [5,6]. Mutation analysis in patients has shown that X-EMD is caused by lack of emerin [4,7]. Mutations in LMNA are predominantly missense and both lamin A/C and emerin seem to be present at nearly normal levels in patients [5,6]. It was suggested that, AD-EMD patients, haploinsuf- ®ciency or a dominant-negative effect caused by mutations in lamin A/C modi®es the nuclear lamina and the nuclear envelope and causes directly or indirectly misplacement or modi®cation of the distribution of emerin [8,9]. Alterna- tively, a third component in addition to emerin and lamin A/C may exist and its cellular distribution may be altered by lack of emerin and mutations in lamin A/C. From this point of view the recently published study of mice, lacking lamin A [10] is of interest as soon after birth the Lmna 2/2 mice develop a severe muscular dystrophy associated with ultra- structural perturbations of the nuclear envelope and mislo- calization of emerin. The genetic ®ndings have shown that the severity of the muscle phenotype in EDM patients is heterogeneous. Patients may present with very severe as well as very mild muscle contractures [2]. In LMNA mutants the cardiac disor- der can be the only clinical phenotype [6,11]. To determine Neuromuscular Disorders 11 (2001) 411±413 0960-8966/01/$ - see front matter q 2001 Elsevier Science B.V. All rights reserved. PII: S0960-8966(00)00206-6 www.elsevier.com/locate/nmd * Corresponding author. Tel.: 139-0382-546340; fax: 139-0382- 422286. E-mail address: toniolo@igbe.pv.cnr.it (D. Toniolo).