The screening for X-linked Emery–Dreifuss muscular dystrophy amongst young patients with idiopathic heart conduction system disease treated by a pacemaker implant M. Vytopil a , S. Vohanka a , J. Vlasinova b , J. Toman c , M. Novak c , D. Toniolo d , R. Ricotti d and Z. Lukas e a Department of Neurology; b Department of Cardiology, University Hospital Brno; c Department of Cardioangiology, St Ann’s University Hospital, Brno, Czech republic; d Institute of Molecular Genetics-CNR, Via Abbiategrasso, Pavia, Italy; and e Department of Pathology, University Hospital Brno, Brno, Czech republic Keywords: heart conduction defects, immunohistochemistry, muscular dystrophy, pacemaker Received 20 October 2003 Accepted 28 December 2003 The X-linked Emery–Dreifuss muscular dystrophy (X-EDMD) is a hereditary muscle disorder associated with cardiac involvement. Sinus node dysfunction and atrioven- tricular conduction defects, typical of X-EDMD, occur in both males and females and may result in sudden cardiac death unless treated by permanent pacing. The objective of the study was to determine the frequency and relevance of X-EDMD in heart con- duction system disease in young individuals treated with a pacemaker implant. The medical history of 3450 paced individuals in the region of South Moravia, Czech republic, was reviewed. Thirty-five patients, 20 males and 15 females, with idiopathic heart conduction disease of onset before age 40 were identified and screened for X-EDMD. Within these 35 individuals, only one male was found to carry a mutation in X-EDMD gene. We conclude that the clinical relevance of X-EDMD in heart con- duction system disease is very low. It should, however, be included into the diagnostic work-up of young male individuals with idiopathic cardiac conduction disturbances. Introduction Emery–Dreifuss muscular dystrophy (EDMD) is a gen- etic disorder characterized by contractures, muscular dystrophy in humeroperoneal distribution and cardiac involvement (Yates, 1997b). EDMD can be inherited as X-linked (X-EDMD), autosomal dominant (AD- EDMD) and autosomal recessive trait (AR-EDMD). The two genes underlying X-linked and autosomal forms are emerin gene and Lamin A/C gene (LMNA), respectively. Heart disease in X-EDMD typically takes form of sinus node dysfunction and atrioventricular conduction defects (Merlini et al., 1986; Voit et al., 1988; Perloff, 1997). In affected males, pacemaker implant becomes almost invariably mandatory before age 35, mean age at pacing being 24 years (Bushby et al., 2003). If not treated by pacing, affected male subjects face high risk of sudden death (40%) (Merlini et al., 1986). Female X-EDMD carriers may suffer from isolated heart disease and some also require pacemaker implant for conduction defects (Boriani et al., 2003). However, detailed charac- teristics of heart involvement in female carriers of one mutated allele of X-EDMD gene need to be elucidated. The X-EDMD gene encodes an ubiquitous protein emerin, localized to inner nuclear membrane. Interest- ingly, X-EDMD cases presenting with cardiac phenotype and no muscle weakness whilst lacking emerin in both tissues, have been described (Yates, 1997a; Vohanka et al., 2001). These reports clearly point toward a crucial role for emerin in cardiac conduction. Although no exact data on epidemiology of X-EDMD is available, it is generally considered a rare disease. However, localiza- tion of emerin to myocytesÕ nuclear membranes and remarkably high sudden cardiac death rate in X-EDMD families, brought up the speculations of higher clinical relevance of emerin gene mutations in isolated heart disease. Moreover, it has been suggested that unrecog- nized cases of the disorder could contribute to sudden unaccountable deaths in otherwise healthy young adults (Emery, 2000). No evidence to support these speculations have, however, been yet documented. To address these issues, we conducted a screening for X-EDMD amongst subjects affected with heart con- duction system disease and treated by insertion of pacemaker before age 40. Our decision to include also females in the screening for this X-linked condition has been supported by recent description of several female carriers presenting with isolated cardiac disease (Boriani et al., 2003). Presumably, the knowledge of frequency of X-EDMD in this cohort would allow for a determination of relevance of emerinopathies in heart conduction disease. Correspondence: Michal Vytopil MD, Neurology Department, Lahey Clinic, 41 Mall Road, Burlington, 01805 MA, USA (tel.: +178 1744 1139; fax: +178 1744 5243; e-mail: michal_vytopil@lahey.org). Ó 2004 EFNS 531 European Journal of Neurology 2004, 11: 531–534