P.4.6 Useful differential diagnostic markers between congenital myotonic dystrophy and X-linked myotubular myopathy

Abstract

Congenital myotonic dystrophy (CDM) and X-linked myotubular myopathy (XLMTM) share common clinical and pathological features at the neonatal stage. Clinically, both CDM and XLMTM patients show reduced fetal movements, polyhydramnios, severe hypotonia and respiratory failure from birth. Pathologically, they commonly show increased number of fibers with internalized nuclei, in addition to peripheral halo. To find useful markers to pathologically differentiate between two disorders, we compared 29 CDM and 40 XLMTM muscle samples younger than 4years of age in terms of difference in the percentage of internalized-nuclei fibers, peripheral halo and type 2C fibers. We also characterized the pathological changes of CDM and XLMTM along the time course. In CDM, the frequency of type 2C fibers is significantly higher and peripheral halo is seen only in early stages. In XLMTM, type 2C fibers are not increased and peripheral halo is seen in age-independent matter. Furthermore, extremely small type 2 fibers are seen at higher ages in XLMTM. These observations suggest that CDM pathology most likely reflects muscle fiber immaturity while XLMTM pathology is produced by structural derangement due to MTM1 mutation.