Histopathologic changes in the extraocular muscle in centronuclear myopathy with a Dynamin 2 mutation

Background: Centronuclear myopathy (CNM) is a rare inherited neuromuscular disorder characterized by centrally placed nuclei in striated muscle. In this report, we describe the histological changes in the extraocular muscle (EOM) from a CNM patient with a mutation in Dynamic 2 (DNM2). Materials and methods: A 33-year-old Caucasian female presented with horizontal diplopia and left exotropia for 6 months prior to which she was asymptomatic. Her past medical history was significant for CNM, diagnosed based on a left quadriceps biopsy with onset of lower extremity weakness in her late 20s. She underwent a left medial rectus (LMR) resection and a left lateral rectus (LLR) recession. The resected muscle was analyzed using light and electron microscopy. Screening for mutations in the DNM2 gene was carried out and the detected mutation was confirmed by direct sequencing. Expression of the DNM2 protein was performed using immunohistochemistry (IHC). Results: Pathology of the EOM revealed 17% centrally located muscle nuclei in contrast to 90% in the quadriceps, variable fiber size, normal ultrastructure of the EOM and normal distribution of DNM2 by IHC. Genetic analysis revealed a heterozygous R369W mutation in the DNM2 gene. Conclusion: The histological changes in the EOM in this CNM patient were mild, which reflected the mild alterations in function seen in this patient. The ophthalmologist seeing patients with new onset strabismus and a history of a myopathy should consider this entity in the differential diagnosis that could be confirmed by a muscle biopsy and mutational analysis.