1100 J.-Y. Lee, J.-H. Min, Y.-H. Hong, et al. A B Fig. 3. Pathological findings of a muscle biopsy from the right tibialis anterior muscle. H&E staining shows centrally located nuclei in nearly all fibers with a marked variation in fiber size (A). NADH tetrazolium reductase staining shows type 1 fiber predominance and hypotrophy, while some fibers reveal radially arranged sarcoplasmic strands (B). Bars=200 m. itive sharp waves in the right tibialis anterior and gastroc- nemius muscles. The patient refused further laboratory tests. DISCUSSION Our patients presented with muscle weakness and atrophy localized mainly in the posterior compartment of the distal lower extremities. Ophthalmoplegia, ptosis, or facial weak- ness was not observed. Similar clinical features were noticed in her mother and daughter. The disease progression appeared to be very slow. At presentation, these patients were believed to have a form of distal myopathy, a group of genetically and pathologically heterogenous diseases characterized by the pat- tern of weakness, age of onset, pattern of inheritance, and mus- cle pathology (8). The pattern of muscle weakness and atrophy in our patients closely resembled Miyoshi myopathy. How- ever, the calf muscle weakness and atrophy typically starts in late teens in Miyoshi myopathy (9), and the inheritance pat- tern is also different. Histopathological findings in our patients clearly showed central nuclei in most fibers, radial arrangement of sarcoplasmic strands around these nuclei, and the predom- inance of and hypotrophy (smallness) of type 1 fibers. All these morphological features are typical findings of CNM (10). The clinical features of ADCNM were reviewed in detail by Wallgren-Pettersson et al. (11). The usual manifestations were slowly progressive generalized muscle weakness, often predom- inantly proximal. Some patients, however, showed additional distal involvement. Occasionally, diffuse hypertrophy (12), calf pseudohypertrophy (13), facial weakness (14), ptosis, or ophthalmoplegia (11) was reported. In a recent study of three ADCNM families (15), two sub- groups were found: two families showed diffuse muscle weak- ness of late onset, whereas the third family presented a diffuse muscle hypertrophy. In that study, it was concluded that no clinical subgroups could be identified based on muscle weak- ness distribution, which was diffuse in most patients with an occasional proximal or distal predominance. An ADCNM fam- ily with a clinical picture simulating facioscapulohumoral syndrome has also been described (16). In our cases, however, the unique feature of the family members was weakness and atrophy of plantar flexors of both legs without ptosis or oph- thalmoparesis, and this pattern was identical in the three af- fected family members. The younger age of onset in subse- quent generations suggested an anticipation phenomenon in our family. With regard to predominant distal weakness of legs, one report mentioned familial cases with weakness and atrophy localized mainly in distal arms and legs. However, these cases showed hypertrophy of calves (13). Recently, Fis- cher et al. reported on the clinical and muscle imaging find- ings of ADCNM patients with dynamin 2 (DNM2) mutations (17). In those patients, muscle computerized tomography re- vealed early and predominant involvement of distal muscles, later affection of the posterior part of the thigh and gluteus minimus muscles. Considering the similarity in clinical pre- sentations between those cases and ours, DNM2 mutations may also be responsible in our cases. Our report demonstrates the expanding clinical heterogeneity of autosomal dominant centronuclear myopathy and empha- sizes the importance of muscle pathology in the definitive dia- gnosis of cases with hereditary myopathies. Further analysis will be necessary to clarify the responsible gene defect in our cases.