CONGENITAL MYOPATHIES (CNM): P.148Centronuclear myopathy with BIN1-like myopathology and DNM2 mutation

Abstract

A limited number of genetically proven cases of BIN1-CNM have been described. DNM2-CNM is more frequent and the main biopsy characteristics is fibers with radiating sarcomeric strands along with nuclear centralization. To present a Brazilian case of DNM2 mutation and muscle biopsy with main features compatible with BIN1-CNM histopathology. Case report. A 58-year-old woman was born as a ``weak child'' with the ``eyes closed''. She had reduced spontaneous movements, delayed motor milestones and a motor limitation in follow other children in motor activities. Although motor weakness she was able to graduate in the university. Additional and more recent complains were hypersomnia and cognitive impairment. Consultation revealed: bilateral symmetrical ptosis and external ophthalmoplegia; motor deficit predominant at pelvic than scapular gilder; symmetric atrophy and weakness in distal lower limb. MFM scale had total score of 65.62% (D1=35.89%; D2=86.11%; D3=85.71%) and FVC was 32%. Recent Montreal cognitive assessment (MoCA) was 22/30. Cerebrospinal fluid showed protein of 82 mg/dL and Pandy positive. Biceps brachii biopsy showed several fibers with nuclear clustering centrally located and myofibers with one central nucleus. Type 1 fiber atrophy, type 2 hypertrophy and few fibers with radiating sarcomeric strands were also seen, thus predicting a CNM with BIN1 mutation. Surprisingly muscle MRI was compatible with DNM2-CNM and a cerebral MRI disclosed meningioma. A panel of new generation sequencing for myopathies showed a pathogenic variant in Ch19:10.904.508C>T (c.1105C>T) diagnosing a DNM2-CNM related. After a successful neurosurgery, the patient never acquired spontaneous ventilation, as was suggestive by MFM and FVC, remained in intensive care unit for four months, had multiples episodes of septicemia and died. Our case expands histopathological phenotypes of DNM2-CNM and reinforce the features of pelvis and legs MRI in DNM2 mutation.