Congenital fiber type disproportion (CFTD) has been related with mutations in ACTA1, SEPN1, RYR1 and tropomyosin 3 (TPM3) genes. Particularly, TPM3 mutation was identified as one of the most frequent cause of CFTD and was also detected in cap myopathy and nemaline myopathy. Herein we report patients of autosomal dominant TPM3 missense mutations with CFTD in a Korean family over twogenerations. Two of our patients, who developed mild muscle weakness in infancy, presented with altered mentality and respiratory distress despite relatively mild limb weakness.
Extremities ; Humans ; Muscle Weakness ; Muscular Diseases ; Mutation, Missense ; Myopathies, Nemaline ; Myopathies, Structural, Congenital ; Respiratory Insufficiency ; Ryanodine Receptor Calcium Release Channel ; Tropomyosin

Centronuclear myopathy (CNM) is a rare congenital myopathy that is pathologically characterized by the centrally locatednuclei in most of the muscle fibers. On clinical examination, dynamin 2 (DNM2)-related CNM typically shows distaldominant muscle atrophy, ptosis, ophthalmoplegia, and contracture. The reported cases of CNM in Caucasian studies showa high prevalence rate of early-onset ptosis and ophthalmoplegia and correlated with the severity of the disease. However,Asian reports show a low prevalence and late-onset ocular symptoms in DNM2-related CNM patients. p.R465W is one ofthe most commonly found mutations in Western countries, and all the cases showed ocular symptoms. The proband and hisdaughter had no ocular symptoms despite harboring the same p.R465W mutation. This family makes us speculate that ocularsymptoms in DNM2-related CNM are influenced by ethnic background. In addition, this is the first familial case of DNM2-related CNM in Korea.
Contracture ; Dynamin II ; Dynamins* ; Humans ; Korea ; Muscular Atrophy ; Muscular Diseases ; Myopathies, Structural, Congenital* ; Ophthalmoplegia ; Prevalence

Acupuncture Therapy ; Adult ; Humans ; Male ; Myopathies, Structural, Congenital ; therapy

BACKGROUND AND PURPOSE: Centronuclear myopathy (CNM) is characterized by the presence of central nuclei within a large number of muscle fibers. Mutations of the dynamin 2 gene (DNM2) are common causes of autosomal dominant or sporadic CNM. The aim of this study was to characterize the clinical and pathological features of CNM relative to the presence of DNM2 mutations. METHODS: Six patients with clinical and pathological features of CNM were recruited. Detailed clinical and pathological findings were analyzed according to the presence of DNM2 mutations. RESULTS: We detected DNM2 mutations in four of the six sporadic CNM patients, and identified the following distinct clinical and pathological features in those patients with DNM2 mutations: preferential involvement of the distal lower limbs, typical nuclear centralization, and radially distributed sarcoplasmic strands in muscle pathology. In contrast, those without DNM2 mutations exhibited rather diffuse muscular involvement, and nuclear internalization and myofibrillar disorganization were more pronounced features of their muscle pathology. CONCLUSIONS: These findings suggest the presence of specific features in Korean CNM patients. A detailed clinical and pathological examination of CNM patients would be helpful for molecular genetic analyses of this condition.
Dynamin II ; Humans ; Lower Extremity ; Molecular Biology ; Muscles ; Myopathies, Structural, Congenital* ; Pathology

X-linked recessive myotubular myopathy (XLMTM) is a severe congenital muscle disorder caused by mutations in the MTM1 gene and characterized by severe hypotonia and generalized muscle weakness in affected males. It is generally a fatal disorder during the neonatal period and early infancy. The diagnosis is based on typical histopathological findings on muscle biopsy, combined with suggestive clinical features. We experienced a case of a newborn who required intubation and ventilator care because of profound hypotonia and respiratory difficulty. The preliminary diagnosis at the time of request for retrieval was hypoxic ischemic encephalopathy, but the infant was clinically reevaluated for generalized weakness and muscle atrophy. Muscle biopsies showed variability in fiber size and centrally located nuclei in nearly all the fibers. We detected an MTM1 gene mutation of c.1261-1C>A in the intron 10 region, and diagnosed the neonate with myotubular myopathy. The same mutation was detected in his mother.
Biopsy ; Humans ; Hypoxia-Ischemia, Brain ; Infant ; Infant, Newborn ; Introns ; Intubation ; Male ; Mothers ; Muscle Hypotonia ; Muscle Weakness ; Muscles ; Muscular Atrophy ; Muscular Diseases ; Myopathies, Structural, Congenital ; Ventilators, Mechanical

BACKGROUND: Myotubular myopathy (MTM) is a congenital myopathy characterized by centrally placed nuclei in muscle fibers. Mutations in the myotubularin 1 gene (MTM1) have been identified in the most of the patients with the X-linked recessive form. CASE REPORT: This report describes two male infants with X-linked MTM (XLMTM). Both patients presented with generalized hypotonia and respiratory difficulties since birth. We did not perform a muscle biopsy in either patient, but their conditions were diagnosed by genetic testing of MTM1. One splicing mutation, c.63+1G>C, and a frame-shift mutation, c.473delA (p. Lys158SerfxX28), were identified. Neither mutation has been reported previously. CONCLUSIONS: Genetic testing for MTM1 is helpful for the differential diagnosis of floppy male infants. We suggest that advanced molecular genetic testing may permit a correct diagnosis while avoiding invasive procedures.
Biopsy ; Diagnosis, Differential ; Genetic Testing ; Humans ; Infant ; Male ; Molecular Biology ; Muscle Hypotonia ; Muscles ; Muscular Diseases ; Myopathies, Structural, Congenital ; Parturition ; Protein Tyrosine Phosphatases, Non-Receptor

Acupuncture Points ; Acupuncture Therapy ; Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Musculoskeletal Pain ; therapy ; Myopathies, Structural, Congenital ; therapy ; Young Adult

Non-progressive congenital myopathy is a group of muscle diseases occurring at birth or during teenage years. A number of new reports of congenital myopathy, such as homogeneous bodies myopathy, muscle quality control myopathy and type 1 fiber predominance have recently been reported, but they lack of sufficient quantity and constant clinico-pathologic manifestations. This paper reports two cases of congenital myopathy with type 1 fiber predominance confirmed by muscle biopsy. The clinical manifestations of the two children (a 4.5-year-old girl and an 11-year-old boy) included non-progressive symptoms of muscle weakness, skeletal deformities and other clinical features of congenital myopathy. The physical examinations showed a long face or figure and funnel chest or kyphosis/scoliosis, high palatal arch and wing-like shoulder. Serum levels of creatine kinase were normal but slightly elevated serum lactate dehydrogenase levels were noted in the two children. The skeletal muscle biopsy by ATPase staining showed that type 1 fibers accounted for more than 90% of the total number of muscle fibers. No other abnormal pathological changes, such as central cores, muscle tube and central nuclei, were found in the two children.
Diagnosis, Differential ; Female ; Humans ; Infant ; Male ; Muscle, Skeletal ; pathology ; Myopathies, Structural, Congenital ; diagnosis ; pathology ; therapy

X-linked myotubular myopathy (XLMTM) is a rare congenital muscle disorder, caused by mutations in the MTM1 gene. Affected male infants present severe hypotonia, and generalized muscle weakness, and the disorder is most often complicated by respiratory failure. Herein, we describe a family with 2 infants with XLMTM which was diagnosed by gene analysis and muscle biopsy. In both cases, histological findings of muscle showed severely hypoplastic muscle fibers with centrally placed nuclei. From the family gene analysis, the Arg486STOP mutation in the MTM1 gene was confirmed.
*Codon, Nonsense ; Humans ; Male ; Muscle Hypotonia/genetics/pathology ; Myopathies, Structural, Congenital/*genetics/pathology ; Pedigree ; Protein Tyrosine Phosphatases, Non-Receptor/*genetics

BACKGROUND AND PURPOSE: At least 100 Ryanodine receptor type 1 (RYR1) mutations associated with malignant hyperthermia (MH) and central core disease (CCD) have been identified, but 2 RYR1 mutations accompanying multiminicore myopathy in an MH and/or CCD family have been reported only rarely. METHODS: Fifty-three members of a large MH family were investigated with clinical, histopathologic, RYR1 mutation, and haplotyping studies. Blood creatine kinase (CK) and myoglobin levels were also measured where possible. RESULTS: Sequencing of the entire RYR1 coding region identified a double RYR1 mutation (R2435H and A4295V) in MH/CCD regions 2 and 3. Haplotyping analysis revealed that the two missense heterozygous mutations (c.7304G>A and c.12891C>T) were always present on a common haplotype allele, and were closely cosegregated with histological multiminicores and elevated serum CK. All the subjects with the double mutation showed elevated serum CK and myoglobin, and the obtained muscle biopsy samples showed multiminicore lesions, but only two family members presented a late-onset, slowly progressive myopathy. CONCLUSIONS: We found multiminicore myopathy with clinical and histological variability in a large MH family with an unusual double RYR1 mutation, including a typical CCD-causing known mutant. These results suggest that multiminicore lesions are associated with the presence of more than two mutations in the RYR1 gene.
Alleles ; Biopsy ; Clinical Coding ; Creatine Kinase ; Haplotypes ; Humans ; Malignant Hyperthermia ; Muscles ; Muscular Diseases ; Myoglobin ; Myopathies, Structural, Congenital ; Myopathy, Central Core ; Ophthalmoplegia ; Ryanodine ; Ryanodine Receptor Calcium Release Channel