Restrictive cardiomyopathy, atrioventricular block and mild to subclinical myopathy in patients with desmin-immunoreactive material deposits

Department of Pathologic Anatomy, Istituto di Ricovero e Cura a Carattere Scientifico, Policlinico San Matteo, Pavia, Italy. Ela2000@iol.it

OBJECTIVES: We present clinical data and heart and skeletal muscle biopsy findings from a series of patients with ultrastructural accumulations of granulofilamentous material identified as desmin. BACKGROUND: Desmin cardiomyopathy is a poorly understood disease characterized by abnormal desmin deposits in cardiac and skeletal muscle. METHODS: Clinical evaluation, endomyocardial and skeletal muscle biopsy, light and electron microscopy and immunohistochemistry were used to establish the presence of desmin cardiomyopathy. RESULTS: Six hundred thirty-one patients with primary cardiomyopathy underwent endomyocardial biopsy (EMB). Ultrastructural accumulations of granulofilamentous material were found in 5 of 12 biopsy samples from patients with idiopathic restrictive cardiomyopathy and demonstrated specific immunoreactivity with anti-desmin antibodies by immunoelectron microscopy. Immunohistochemical findings on light microscopy were nonspecific because of a diffuse intracellular distribution of desmin. All five patients had atrioventricular (AV) block and mild or subclinical myopathy. Granulofilamentous material was present in skeletal muscle biopsy samples in all five patients, and unlike the heart biopsy samples, light microscopic immunohistochemical analysis demonstrated characteristic subsarcolemmal desmin deposits. Two patients were first-degree relatives (mother and son); another son with first-degree AV block but without myopathy or cardiomyopathy demonstrated similar light and ultrastructural findings in skeletal muscle. Electrophoretic studies demonstrated two isoforms of desmin--one of normal and another of lower molecular weight--in cardiac and skeletal muscle of the familial cases. CONCLUSIONS: Desmin cardiomyopathy must be considered in the differential diagnosis of restrictive cardiomyopathy, especially in patients with AV block and myopathy. Diagnosis depends on ultrastructural examination of EMB samples or light microscopic immunohistochemical studies of skeletal muscle biopsy samples. Familial desminopathy may manifest as subclinical disease and may be associated with abnormal isoforms of desmin.

This article has been cited by other articles:

				E. Arbustini, M. Pasotti, A. Pilotto, C. Pellegrini, M. Grasso, S. Previtali, A. Repetto, O. Bellini, G. Azan, M. Scaffino, et al. Desmin accumulation restrictive cardiomyopathy and atrioventricular block associated with desmin gene defects Eur J Heart Fail, August 1, 2006; 8(5): 477 - 483. [Abstract] [Full Text] [PDF]

				J. J. Gard, K. Yamada, K. G. Green, B. C. Eloff, D. S. Rosenbaum, X. Wang, J. Robbins, R. B. Schuessler, K. A. Yamada, and J. E. Saffitz Remodeling of gap junctions and slow conduction in a mouse model of desmin-related cardiomyopathy Cardiovasc Res, August 15, 2005; 67(3): 539 - 547. [Abstract] [Full Text] [PDF]

				E. Arbustini, A. Repetto, M. Pasotti, G. Azan, C. Opasich, C. Campana, A. Gavazzi, R. Ferrari, and L. Tavazzi Cardiomyology: an attempt to link structural cardiac and skeletal muscle damage in patients with dilated cardiomyopathy Eur. Heart J. Suppl., November 1, 2004; 6(suppl_F): F40 - F53. [Abstract] [Full Text] [PDF]

				M. Der Perng, S. F. Wen, P. van den IJssel, A. R. Prescott, and R. A. Quinlan Desmin Aggregate Formation by R120G {alpha}B-Crystallin Is Caused by Altered Filament Interactions and Is Dependent upon Network Status in Cells Mol. Biol. Cell, May 1, 2004; 15(5): 2335 - 2346. [Abstract] [Full Text] [PDF]

				X. Wang, R. Klevitsky, W. Huang, J. Glasford, F. Li, and J. Robbins {alpha}B-Crystallin Modulates Protein Aggregation of Abnormal Desmin Circ. Res., November 14, 2003; 93(10): 998 - 1005. [Abstract] [Full Text] [PDF]

				E. Arbustini, A. Pilotto, A. Repetto, M. Grasso, A. Negri, M. Diegoli, C. Campana, L. Scelsi, E. Baldini, A. Gavazzi, et al. Autosomal dominant dilated cardiomyopathy with atrioventricular block: a lamin A/C defect-related disease J. Am. Coll. Cardiol., March 20, 2002; 39(6): 981 - 990. [Abstract] [Full Text] [PDF]

				X. Wang, H. Osinska, G. W. Dorn II, M. Nieman, J. N. Lorenz, A. M. Gerdes, S. Witt, T. Kimball, J. Gulick, and J. Robbins Mouse Model of Desmin-Related Cardiomyopathy Circulation, May 15, 2001; 103(19): 2402 - 2407. [Abstract] [Full Text] [PDF]

				A. Gavazzi, A. Repetto, L. Scelsi, C. Inserra, M.L. Laudisa, C. Campana, C. Specchia, B. Dal Bello, M. Diegoli, L. Tavazzi, et al. Evidence-based diagnosis of familial non-X-linked dilated cardiomyopathy. Prevalence, inheritance and characteristics Eur. Heart J., January 1, 2001; 22(1): 73 - 81. [Abstract] [PDF]

				E. Arbustini, P. Morbini, A. Pilotto, A. Gavazzi, and L. Tavazzi Familial dilated cardiomyopathy: from clinical presentation to molecular genetics Eur. Heart J., November 2, 2000; 21(22): 1825 - 1832. [PDF]

				E. Arbustini, M. Diegoli, P. Morbini, B. Dal Bello, N. Banchieri, A. Pilotto, F. Magani, M. Grasso, J. Narula, A. Gavazzi, et al. Prevalence and characteristics of dystrophin defects in adult male patients with dilated cardiomyopathy J. Am. Coll. Cardiol., June 1, 2000; 35(7): 1760 - 1768. [Abstract] [Full Text] [PDF]

				X. Wang, H. Osinska, R. Klevitsky, A. M. Gerdes, M. Nieman, J. Lorenz, T. Hewett, and J. Robbins Expression of R120G-{alpha}B-Crystallin Causes Aberrant Desmin and {alpha}B-Crystallin Aggregation and Cardiomyopathy in Mice Circ. Res., July 6, 2001; 89(1): 84 - 91. [Abstract] [Full Text] [PDF]