Sporadic centronuclear myopathy with muscle pseudohypertrophy, neutropenia, and necklace fibers due to a DNM2 mutation

Abstract

Dynamin 2 gene (DNM2) mutations result in an autosomal dominant centronuclear myopathy (CNM) and a Charcot-Marie-Tooth (CMT) neuropathy. DNM2-CMT but not DNM2-CNM patients were noted to have neutropenia. We here report a man with paravertebral muscles hypertrophy and mild neutropenia. His muscle biopsy was typical for CNM with additional "necklace" fibers. Sequencing of DNM2 revealed a known heterozygous c.1269C>T (p.Arg369Trp) mutation. Necklace fibers were considered as a pathological hallmark of late onset X-linked CNM due to mutations in MTM1 but have not been observed in DNM2-CNM. The findings broaden the features of DNM2-myopathy.

Fig.1

(A) Abdominal CT scan reveals fatty infiltration and enlargement of paraspinal (arrow) and anterior abdominal muscles (arrowhead). (B) The patient with bilateral, paraspinal muscle (asterisk) hypertrophy. (C) Hematoxylin and eosin section displays numerous myofibers harboring centrally-place nuclei. Arrow points to a single necrotic fiber replaced by macrophages. There is a moderate to marked increase in perimysial fatty (asterisk) and a mild increase in endomysial fibrous connective tissue. (D) In NADH dehydrogenase-reacted section, some fibers show radial arrangement of the myofibrils and harbor central nuclei (arrow). Scattered myofibers with centrally-located nuclei displays peripheral accentuation of enzyme reactivity in a necklace-like pattern (arrowhead). The necklaces were positive for Sarcoplasmic/Endoplasmic reticulum calcium ATPase 2 (SERCA2) (inlet). (E) Chromatogram shows a heterozygous c.1269C>T substitution in DNM2 exon 8 causing p.Arg369Trp. Bar: 100 μm in C and 50 μm in D.