Importance of Biopsy Despite Genetic Testing Advancements, a Rare Case of Late-onset Congenital Centronuclear Myopathy (P7-11.007)

Genetic testing is becoming more accessible and less expensive in helping diagnose rare neuromuscular diseases. However, we see the importance of pathology despite genetic testing advancements as seen in this unique case report. A 67-year-old male presented with 3 years of truncal and proximal limb weakness. Childhood history was significant for delayed walking and talking milestones. He also has two sisters, one of which has two sons with an unknown “muscular disorder”. Exam notable for myopathic facies, wrist and ankle contractures, pectoral creases, unable to do a deep squat, with a modified Gowers’ sign to stand. EMG/NCS showed a non-irritable myopathy providing evidence of a clinical picture suspected of a late-onset congenital myopathy. The neuromuscular gene panel showed a hemizygous pathogenic mutation of the MTM1 gene and an unknown zygosity pathogenic mutation of the NEB gene. Muscle biopsy of the left deltoid revealed increased internal nuclei often centrally located with myopathic fiber size variation and type I fiber smallness consistent with X-linked MTM1 centronuclear myopathy. This case demonstrates the value of muscle biopsy as a necessary diagnostic tool, especially in the setting of unclear genetic testing results. In addition, this is a rare case of a congenital centronuclear myopathy being diagnosed late in life. The majority of patients with this X-linked MTM1 die in childhood with 50% mortality before 18 months of age. The patient has a mild phenotype compared to the typical progression of this illness.