Preferential central nucleation of type 2 myofibers is an invariable feature of myotonic dystrophy type 2

Abstract

The clinical features of myotonic dystrophy type 1 (DM1) and type 2 (DM2) may present striking similarity, whereas, in some cases, the DM2 phenotype may be so mild that the diagnosis may be missed. Therefore, the identification of disease-specific histopathological patterns for DM1 and DM2 may help clinicians to correctly address genetic studies. We performed a comparative morphological and morphometric analysis on muscle biopsies from 10 DM1 and 11 DM2 patients, comparing type 1 and type 2 fibers as to: fiber type predominance, transverse diameter, atrophy and hypertrophy factors, and prevalence of central nuclei. In DM1 cases we observed preferential type 1 fiber atrophy and a higher prevalence of central nucleation among type 1 fibers in all cases. In DM2 muscle biopsies, high rates of atrophic and hypertrophic type 2 fibers were observed in most cases, and preferential central nucleation in type 2 fibers was present in all cases. As opposed to DM1, in which type 1 fibers display most of the histological changes, preferential atrophy and hypertrophy of type 2 fibers may be considered as markers of DM2. A higher prevalence of central nuclei among hypertrophic type 2 fibers has a predictive value for the diagnosis of DM2. Thus, morphometric and fiber type-based histological analysis of muscle biopsies may help differentiate between DM1 and DM2 and guide molecular analysis.

Overexpression of CUGBP1 in Skeletal Muscle from Adult Classic Myotonic Dystrophy Type 1 but Not from Myotonic Dystrophy Type 2

“…Muscle histopathology of most of DM1 and DM2 patients examined in this work showed the characteristic myopathic features of these diseases. Moreover, in DM2 muscles the mainly affected fiber type is type 2 fibers as previously reported by other authors [29], [60], [61]. However this is true for DM1 and DM2 patient groups showing the more severe multisystemic phenotypes but not for the groups of paucisymptomatic patients, i.e.…”

Expanded CCUG repeat RNA expression in Drosophila heart and muscle trigger Myotonic Dystrophy type 1-like phenotypes and activate autophagocytosis genes

“…In both diseases, affected muscles show central nuclei, a reduction in the number and diameter of specific fiber types, fibrosis and adipose deposition. DM2 is specifically characterized by the presence of atrophic fibers with nuclear clumps even before the muscle weakness appearance as well as by a predominant type 2 fiber atrophy 59, 60 . In DM2, cardiac abnormalities have also been reported to be similar to those described in DM1, including conduction disturbances, cardiac arrhythmias and sudden death 26, 61–63 .…”

Extraocular Muscles in Patients With Infantile Nystagmus

“…Central nucleation has long been associated with muscle disease and muscle injury and regeneration. 17,18 Based on the increased percentage of centrally nucleated myofibers, the EOMs from these patients seem to be undergoing more rapid cycles of degeneration and regeneration than are those of controls. Although a dynamic process cannot be assessed from histologic specimens, the presence of central nucleation was a consistent finding in the patients’ muscles, suggesting that this indeed may be the case.…”