Myotonia in DNM2-related centronuclear myopathy

• Published in: Journal of Neural Transmission Vol. 121; no. 5; pp. 549 - 553
• Main Authors: Dabby, Ron, Sadeh, Menachem, Gilad, Ronit, Jurkat-Rott, Karin, Lehmann-Horn, Frank, Leshinsky-Silver, Esther
• Format: Journal Article
• Language: English
• Published: Vienna Springer Vienna 01.05.2014; Springer Nature B.V
• Subjects: Adult; Base Sequence; Chloride Channels - genetics; DNA Mutational Analysis; Dynamin II - genetics; Electromyography; Female; Humans; Medicine; Medicine & Public Health; Muscle, Skeletal - pathology; Muscle, Skeletal - physiopathology; Myopathies, Structural, Congenital - complications; Myopathies, Structural, Congenital - genetics; Myopathies, Structural, Congenital - pathology; Myopathies, Structural, Congenital - physiopathology; Myotonia - complications; Myotonia - genetics; Myotonia - pathology; Myotonia - physiopathology; Myotonin-Protein Kinase - genetics; NAV1.4 Voltage-Gated Sodium Channel - genetics; Neurology; Neurology and Preclinical Neurological Studies - Original Article; Neurosciences; Psychiatry; RNA-Binding Proteins - genetics; ); Centronuclear myopathy; Electromyography; Dynamin 2; Myotonia; Charcot–Marie–Tooth (CMT) neuropathy
• ISSN: 0300-9564; 1435-1463; 1435-1463
• DOI: 10.1007/s00702-013-1140-8

Centronuclear myopathy (CNM) is a rare hereditary myopathy characterized by centrally located muscle fiber nuclei. Mutations in the dynamin 2 ( DNM2 ) gene are estimated to account for about 50 % of CNM cases. Electromyographic recordings in CNM may show myopathic motor unit potentials without spontaneous activity at rest. Myotonic discharges, a distinctive electrical activity caused by membrane hyperexcitability, are characteristic of certain neuromuscular disorders. Such activity has been reported in only one CNM case without a known genetic cause. We sequenced the DNM2 gene and the genes associated with myotonia ( CLCN1, SCN4A, DMPK and ZNF9 ) in a sporadic adult patient with CNM and myotonic discharges. Sequencing the entire coding region and exon–intron boundaries revealed a heterozygous c.1106g-a substitution in exon 8, resulting in a R369Q change in the DNM2 . Sequencing the CLCN1, SCN4A, DMPK and ZNF9 genes ruled out mutations in these genes. This is the first report of DNM2 -related CNM presenting with myotonia. The diagnosis of CNM should be considered in patients with myotonic discharges of an unknown cause.