Abstract
Centronuclear myopathy (CNM) is a group of rare genetic muscle disorders characterized by muscle fibers with centrally located nuclei. The most common forms of CNM have been attributed to X-linked recessive mutations in the MTM1 gene; autosomal-dominant mutations in the DNM2 gene-encoding dynamin-2, the BIN1 gene; and autosomal-recessive mutations in BIN1, RYR1, and TTN genes. Dominant CNM due to DNM2 mutations usually follows a mild clinical course with the onset in adolescence. Currently, around 35 mutations of the DNM2 gene have been identified in CNM; however, the underlying molecular mechanism of DNM2 mutation in the pathology of CNM remains elusive, and the standard clinical characteristics have not yet been defined. Here, we describe the case of a 17-year-old female who presented with proximal muscle weakness along with congenital anomalous pulmonary venous connection (which has not been described in previous cases of CNM), scoliosis, and lung disease without a significant family history. Her creatine kinase level was normal. Histology, special stains, and electron microscope findings on her skeletal muscle biopsy showed CNM with the characteristic features of a DNM2 mutation, which was later confirmed by next-generation sequencing. This case expands the known clinical and pathological findings of CNM with DNM2 gene mutation.
Highlights
Centronuclear myopathy (CNM) is a rare congenital myopathy, which was first described as myotubular myopathy by Spiro et al.[1] in 1966
CNM is a rare congenital myopathy, which can be diagnosed based on histology
Three forms of the disease are clinically recognized: (i) the X-linked severe neonatal form, which is caused by MTM1 mutation; (ii) the autosomal recessive childhood onset form, which is usually caused by bridging integrator 1 gene (BIN1) mutation; and (iii) the autosomal dominant adult-onset form, which is caused by dynamin 2 (DNM2) mutation
Summary
Centronuclear myopathy (CNM) is a rare congenital myopathy, which was first described as myotubular myopathy by Spiro et al.[1] in 1966. Abnormal genital development occurs.[9] Heterozygous female carriers may present with limb girdle and facial weakness.[10] Mutations in MTM1 have been recognized as the underlying cause of atypical forms of XLMTM in newborn boys, female infants, and adult men and women, which presents a histological alteration in some muscle fibers that resemble a necklace (“necklace fibers”).[11] Muscle biopsies from XLMTM patients show numerous fibers with central nuclei resembling myotubes, which are frequently surrounded by a paler peripheral halo. It is caused by a mutation in dynamin 2 (DNM2) on chromosome 19.20 The most prominent histopathological features include the frequency of centrally located nuclei
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