Autosomal dominant myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy linked to chromosome 10q

Twenty-one members of a Swedish family suffering from myopathy and cardiomy opathy underwent neurological and cardiological investigations. Medical cha rts of 2 affected deceased patients were reviewed. Twelve patients had myop athy. The distribution of weakness was axial in mildly affected, axial and predominantly distal in moderately affected, and generalized in severely af fected patients. The electromyogram showed signs of myopathy in 10 patients . Muscle biopsy specimens showed myopathic changes, rimmed vacuoles, and ac cumulation of desmin, dystrophin, and other proteins. Electron microscopy r evealed granulofilamentous changes and disorganization of myofibrils. Sever al patients had episodes of chest pain or palpitations. Three men had arrhy thmogenic right ventricular cardiomyopathy. Nonsustained ventricular tachyc ardia, atrial flutter, and dilatation of the ventricles mainly affecting th e right ventricle were documented. Two of them had a pacemaker implanted be cause of atrioventricular block and sick sinus syndrome. Inheritance is aut osomal dominant with variable onset and severity of skeletal muscle and car diac involvement. Linkage analysis of candidate chromosomal regions showed a maximum 2-point LOD score of 2.76 for marker locus D10S1752 on chromosome 10q. A multipoint peak LOD score of 3.06 between markers D10S605 and D10S2 15 suggests linkage to chromosome 10q22.3, and this region may harbor a gen etic defect for myofibrillar myopathy with arrhythmogenic right ventricular cardiomyopathy.