Discussion.

The clinicopathologic hallmark in our patient with BIN1-related AR-CNM was a childhood-onset, diffuse, slowly progressive myopathy with delayed psychomotor milestones, ptosis, mental retardation, and respiratory insufficiency. A postsynaptic neuromuscular transmission defect and abundant myotonic discharges were present. In addition to typical CNM features, muscle biopsy was characterized by large-sized groups of centralized nuclei in many fibers, extensive myofibrillar disorganizations surrounding central nuclei, and radial sarcoplasmic strands only in rare fibers. These histopathologic features differentiate with DNM2-associated CNM. Clinically, our patient shared several features with DNM2-CNM 2, 3: ptosis, external ophthalmoparesis, normal cardiac function, and slow disease progression. Mild cognitive impairment has also rarely been reported in DNM2-CNM. In contrast to our case, DNM2-mutated patients with CNM show either predominant proximal weakness or distal muscle involvement that might precede proximal weakness, and respiratory function is mostly normal. 3 Myotonic discharges without clinical myotonia have been reported in patients with CNM in the premolecular era, 5 and in at least one of them 5 a DNM2 mutation was identified in the meantime. Muscle imaging in DNM2-associated CNM 3 is characterized by early involvement of ankle plantar flexors, followed by posterior and eventually anterior compartment of the thighs, a different pattern than that seen in our patient.