A 16-year-old girl presented with progressive bilateral lower limb weakness for 3 years. Examination revealed tongue fasciculations, muscle wasting, and extensor plantar responses. Nerve conduction studies revealed motor-sensory axonal polyneuropathy. MRI brain showed multifocal cavitating white matter disease with diffusion restriction (figures 1 and 2). Exome sequencing revealed heterozygous missense variation c.775C>T(p.Arg259Cys) in exon 8 of the MFN2 gene, pathogenic for Charcot-Marie-Tooth disease 2A (CMT2A).
Axial T2-weighted images (A–C) show discrete hyperintense foci in periventricular and deep cerebral white matter. Axial T2-FLAIR images (D and E) show suppression of signal within the lesions suggesting cystic nature (white arrows). A nonsuppressed lesion (F) was seen in the left temporal lobe (black arrow).
Axial diffusion-weighted images (A–C) and corresponding apparent diffusion coefficient maps (D–F) show diffusion restriction along the walls of some cystic lesions (white arrows) and solid diffusion restriction in the left temporal lobe lesion (black arrows). Spinal cord was normal (images not shown).
Dominant mutations of MFN2 (encoding mitochondrial protein mitofusin-2) cause a disorder of mitochondrial DNA maintenance1 resulting in axonal sensorimotor neuropathy. Nonspecific white matter alterations are reported in few patients with CMT2A.2 Multifocal cavitating leukodystrophy may be seen rarely.
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Footnotes
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