Search

Myotonia is characterized by hyperexcitability of the muscle cell membrane. Myotonic disorders are divided into two main categories: non-dystrophic and dystrophic myotonias. The non-dystrophic myotonias involve solely the muscle system, whereas the dystrophic myotonias are characterized by multisystem involvement and additional muscle weakness. Each category is further subdivided into different groups according to additional clinical features or/and underlying genetic defects. However, the phenotypes and the pathological mechanisms of these myotonic disorders are still not entirely understood. Currently, four genes are identified to be involved in myotonia: the muscle voltage-gated sodium and chloride channel genes SCN4A and CLCN1, the myotonic dystrophy protein kinase (DMPK) gene, and the CCHC-type zinc finger, nucleic acid binding protein gene CNBP. Additional gene(s) and/or modifying factor(s) remain to be identified. In this study, we investigated a large Norwegian family with clinically different presentations of myotonic disorders. Molecular analysis revealed CCTG repeat expansions in the CNBP gene in all affected members, confirming that they have myotonic dystrophy type 2. However, a CLCN1 mutation c.1238C>G, causing p.Phe413Cys, was also identified in several affected family members. Heterozygosity for p.Phe413Cys seems to exaggerate the severity of myotonia and thereby, to some degree, contributing to the pronounced variability in the myotonic phenotype in this family., (© 2011 John Wiley & Sons A/S.)

Muscle biopsy specimens from the myotonic goat, an animal model of heritable myotonia, were examined histochemically and by electron microscopy. After Periodic acid-Schiff (PAS) staining with diastase digestion, there was increased PAS-positive material within myotonic goat fibers, as compared with those of normal goats. Myotonic muscle stained with alizarin red S, a histochemical stain for calcium, also had an increased staining reaction when compared with muscle from normal goats. Several ultrastructural abnormalities were found in myotonic goat muscle using routine osmium and uranyl acetate staining. These included increased density of the t-tubules, electron-dense material within t-tubules, proliferation and dilatation of sarcotubular elements, and abnormal mitochondria in the myotonic biopsy specimens. To further study muscle ultrastructure, ruthenium red and lanthanum were used as electron microscopic stains with specificity for membranes. There was increased density of the sarcolemma and t-tubules in myotonic muscle stained with ruthenium red as compared to normal, and lanthanum produced a darker staining reaction of the myotonic goat sarcolemma. The histochemical and ultrastructural differences between normal and myotonic goat muscle were interpreted to be consistent with a morphologic basis for the abnormal contraction-relaxation properties characteristic of myotonia.

The nosographic relationship between Thomsen's and Steinert's disease is still uncertain. There is not agreement in the literature whether these are two different diseases or just different stages in the evolution of a single one. Four members of a family in two generations have been studied: two have a typical Steinert's, one a Thomsen's disease and one a clinical pattern that cannot be clearly considered neither of the first nor of the second type. In this patient a generalized muscular hypertrophy was followed, at the age of 54, by a generalized impairment of the muscular trophism and evolved into a severe wasting. This may be interpreted as an evolution of Thomsen's into a Steinert's disease. Furthermore, the presence in the same family of cases of both Thomsen's and Steinert's disease supports the hypothesis of a single disease. The present study suggests that Thomsen's and Steinert's diseases could be two clinical varieties of a single disease in different stages of development. This conclusion is supported by the similarity in the electromyographic patterns and in the histological picture from muscle biopsy of all patients examined.

The authors have reported the results of examination by electron microscopy of two muscle biopsy specimens from cases of myotonia congenita and three cases of myotonia dystrophica. They have stated that "peripheral annular formation" was a frequently observed alteration in the myotonia congenita cases. In the myotonia dystrophica cases there were additionally disorganized myofibrils in the subsarcolemmal region and inclusion body vacuoles morphologically connected with the sarcolemma. The term "peripheral annular formation" refers to the situation in which the peripheral myofibrils of the muscle fiber fracture and the fragments retract and form a helical sheath around the central myofibrils of the same muscle fiber.