Sudden cardiac death in a patient with lamin A/C mutation in the absence of dilated cardiomyopathy or conduction disease

Dilated cardiomyopathy (DCM) is a frequent form among the cardiomyopathies and displays a very heterogeneous etiology. It is a familial disease in about one-third of DCM cases [8, 14, 16]. More than 20 DCM candidate genes were already identified [2, 4], but the genetic defects in the large majority of familial cases are still unknown. LMNA is among the most common genes affected in familial DCM and is coding for lamin A/C, which is a ubiquitous component of the nuclear skeleton and involved in the regulation of gene expression. However, there are many other non-cardiac diseases like Emery-Dreifuss muscular dystrophy (EDMD2; OMIM 181350), Limb-girdle muscular dystrophy type 1B (LGMD1B; OMIM 159001), Dunnigantype familial partial lipodystrophy (OMIM 151660), Charcot-Marie-Tooth disease (CMT2B1; OMIM 605588), Hutchinson-Gilford progeria syndrome (HGPS; OMIM 176670) and restrictive dermopathy (OMIM 275210), which can result from defects in this gene and are summarized under the term laminopathies [5]. DCM caused by LMNA mutations is attributed to a characteristic phenotype showing atrial fibrillation, skeletal muscle involvement, cardiac conduction defects and a high incidence of sudden death [3, 9, 20, 25, 26]. Due to these complications, DCM patients with LMNA mutations are reported to have a worse prognosis compared to other DCM patients [23, 28] and a nearly complete disease penetrance with disease expression between 20 and 60 years of age [19]. It is estimated that up to 5% of all DCM cases are caused by LMNA mutations [24]. Here we report about a family with a gene mutation in the lamin A/C gene (LMNA) with the incidence of sudden cardiac death even before the manifestation of dilated cardiomyopathy. A 32-year-old woman presented at the outpatient department after a sudden loss of consciousness for seconds, while she was driving a car on a motorway. There were no prodromi before this event and no diseases in the medical history. However, she reported about a premature death of her father at the age of 42 years, which was interpreted as related to myocardial infarction. There were no abnormal clinical findings and the ECG was interpreted as normal. Echocardiography revealed regular findings, with the exception, that in the apex of the right ventricle a small sacculation was suspected. In regard to the clinical event and family history further thorough examination was initiated (Table 1)