centronuclear myopathy ( cnm ) is a congenital myopathy with the characteristic morphology of centrally located nuclei in the vast majority of muscle fibers . after the disease was first reported in 1966 by spiro et al . as myotubular myopathy ( 1 ) , three distinctive inheritance patterns in cnm have been discovered , i.e. , a severe neonatal onset with x - linked recessive type ( xrcnm ) , a less severe infantile or childhood onset with autosomal recessive type ( arcnm ) , and a milder late childhood or adult onset with autosomal dominant type ( adcnm ) ( 2 ) . to date , six cases have been reported in korea ( 3 - 7 ) . xrcnm is a relatively uniform disorder clinically characterized by severe hypotonia , rapidly progressive muscle weakness , and respiratory failure at birth often leading to early mortality . this form is also called as x - linked myotubular myopathy . however , unlike xrcnm , the clinical features of autosomal dominant cnm ( adcnm ) are quite variable among reported families . we describe unusual manifestations of adcnm with preferential involvement of the distal lower extremities , especially in the gastrocnemius and soleus muscles , with a brief review of clinical features of previously reported adcnm . a 49-yr - old woman presented with slowly progressive weakness of both legs , which had developed at the age of forty . initially , she felt her gait waddling slightly , and she had difficulty in climbing stairs and standing on her toes . weakness was dominant in the distal part of both lower extremities , which did not affect daily activities . she was a product of a full - term spontaneous vaginal delivery , without perinatal or developmental problems . she had no history of medical illness or drug use , including steroids and herb medicines . one was an 18-yr - old girl , who developed similar symptoms at the age of fifteen ( see case 2 ) , and the other , a 15-yr - old girl , was not affected . her 70-yr - old mother had the same gait abnormality and progressive weakness and wasting of both calf muscles , which occurred in late - fifties without impairment of daily activities . muscle powers of the ankle dorsiflexors and plantar flexors were medical research council ( mrc ) grade 5- and 4 , respectively . 1 ) . deep tendon reflexes were hypoactive on both upper and lower extremities without pathological reflexes . she had a mild waddling gait , and toe gait was more impaired than heel gait . examinations of cranial nerves and sensations revealed no abnormality , and her cognitive function was normal . her serum creatine kinase ( ck ) was slightly elevated to 304 iu / l ( normal , < 270 iu / l ) , but other routine laboratory tests , including thyroid function , were all within normal limits . needle electromyography showed low - amplitude , short - duration , polyphasic motor unit potentials along with fibrillations and positive sharp waves in the left vastus lateralis , tibialis anterior , and gastrocnemius muscles . the magnetic resonance image of the lower extremities revealed predominant atrophy and fatty changes of bilateral gastrocnemius and soleus muscles ( fig . a muscle biopsy from the right tibialis anterior showed centrally located nuclei in the vast majority of muscle fibers with marked fiber size variations . a moderate degree of endomysial fibrosis and fatty changes were also noted . nadh tetrazolium reductase staining showed type 1 fiber predominance ( more than 95% ) and hypotrophy , while some fibers revealed radially arranged sarcoplasmic strands ( fig . electron microscopy also showed marked fiber size variations and centrally located nuclei in myofibers frequently . the 18-yr - old daughter of case 1 complained of difficulty in walking and during physical exercise from the age of 15 . the neurological examinations showed a weakness in the ankle dorsiflexors and plantar flexors ( mrc grade 5- ) , impaired toe and heel gaits , mild atrophy of both calf muscles , and hypoactive tendon reflexes . needle electromyography revealed low - amplitude , short - duration , polyphasic motor unit potentials along with fibrillations and positive sharp waves in the right tibialis anterior and gastrocnemius muscles . a 49-yr - old woman presented with slowly progressive weakness of both legs , which had developed at the age of forty . initially , she felt her gait waddling slightly , and she had difficulty in climbing stairs and standing on her toes . weakness was dominant in the distal part of both lower extremities , which did not affect daily activities . she was a product of a full - term spontaneous vaginal delivery , without perinatal or developmental problems . she had no history of medical illness or drug use , including steroids and herb medicines . one was an 18-yr - old girl , who developed similar symptoms at the age of fifteen ( see case 2 ) , and the other , a 15-yr - old girl , was not affected . her 70-yr - old mother had the same gait abnormality and progressive weakness and wasting of both calf muscles , which occurred in late - fifties without impairment of daily activities . muscle powers of the ankle dorsiflexors and plantar flexors were medical research council ( mrc ) grade 5- and 4 , respectively . 1 ) . deep tendon reflexes were hypoactive on both upper and lower extremities without pathological reflexes . she had a mild waddling gait , and toe gait was more impaired than heel gait . examinations of cranial nerves and sensations revealed no abnormality , and her cognitive function was normal . her serum creatine kinase ( ck ) was slightly elevated to 304 iu / l ( normal , < 270 iu / l ) , but other routine laboratory tests , including thyroid function , were all within normal limits . needle electromyography showed low - amplitude , short - duration , polyphasic motor unit potentials along with fibrillations and positive sharp waves in the left vastus lateralis , tibialis anterior , and gastrocnemius muscles . the magnetic resonance image of the lower extremities revealed predominant atrophy and fatty changes of bilateral gastrocnemius and soleus muscles ( fig . a muscle biopsy from the right tibialis anterior showed centrally located nuclei in the vast majority of muscle fibers with marked fiber size variations . a moderate degree of endomysial fibrosis and fatty changes were also noted . nadh tetrazolium reductase staining showed type 1 fiber predominance ( more than 95% ) and hypotrophy , while some fibers revealed radially arranged sarcoplasmic strands ( fig . electron microscopy also showed marked fiber size variations and centrally located nuclei in myofibers frequently . the 18-yr - old daughter of case 1 complained of difficulty in walking and during physical exercise from the age of 15 . the neurological examinations showed a weakness in the ankle dorsiflexors and plantar flexors ( mrc grade 5- ) , impaired toe and heel gaits , mild atrophy of both calf muscles , and hypoactive tendon reflexes . needle electromyography revealed low - amplitude , short - duration , polyphasic motor unit potentials along with fibrillations and positive sharp waves in the right tibialis anterior and gastrocnemius muscles . our patients presented with muscle weakness and atrophy localized mainly in the posterior compartment of the distal lower extremities . 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 pattern of weakness , age of onset , pattern of inheritance , and muscle pathology ( 8) . the pattern of muscle weakness and atrophy in our patients closely resembled miyoshi myopathy . however , the calf muscle weakness and atrophy typically starts in late teens in miyoshi myopathy ( 9 ) , and the inheritance pattern 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 predominance of and hypotrophy ( smallness ) of type 1 fibers . the clinical features of adcnm were reviewed in detail by wallgren - pettersson et al . the usual manifestations were slowly progressive generalized muscle weakness , often predominantly 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 subgroups were found : two families showed diffuse muscle weakness 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 weakness distribution , which was diffuse in most patients with an occasional proximal or distal predominance . an adcnm family 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 ophthalmoparesis , and this pattern was identical in the three affected family members . the younger age of onset in subsequent 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 , fischer et al . reported on the clinical and muscle imaging findings of adcnm patients with dynamin 2 ( dnm2 ) mutations ( 17 ) . in those patients , muscle computerized tomography revealed 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 presentations between those cases and ours , dnm2 mutations our report demonstrates the expanding clinical heterogeneity of autosomal dominant centronuclear myopathy and emphasizes the importance of muscle pathology in the definitive diagnosis of cases with hereditary myopathies .
centronuclear myopathies are clinically and genetically heterogenous diseases with common histological findings , namely , centrally located nuclei in muscle fibers with a predominance and hypotrophy of type 1 fibers . 
 we describe two cases from one family with autosomal dominant centronuclear myopathy with unusual clinical features that had initially suggested distal myopathy . 
 clinically , the patients presented with muscle weakness and atrophy localized mainly to the posterior compartment of the distal lower extremities . 
 magnetic resonance imaging revealed predominant atrophy and fatty changes of bilateral gastrocnemius and soleus muscles . 
 this report demonstrates the expanding clinical heterogeneity of autosomal dominant centronuclear myopathy .