Early Onset Severe Axonal Neuropathy Associated with Optic Atrophy and Vocal Cord Paresis Due to a Mitofusin 2 Mutation

  • Dr Eppie Yiu, Royal Children's Hospital Melbourne, Australia
  • Dr Lloyd Shield, Royal Children's Hospital Melbourne, Australia
  • Dr Leslie Roberts, St Vincent's Hospital Melbourne, Australia
  • A/Prof Justin O'Day, University of Melbourne, Dept of Ophthalmology, Australia
  • Dr Belinda Chong, Murdoch Children’s Research Institute, Australia
  • Dr Desirée du Sart, Murdoch Children’s Research Institute, Australia
  • Dr Monique Ryan, Royal Children's Hospital Melbourne, Australia

    • Objective: Mutations in the mitofusin 2 (MFN2) gene have been described in Charcot-Marie-Tooth disease Type 2A (CMT 2A), hereditary motor and sensory neuropathy Type VI (HMSN VI), and the Ouvrier form of axonal neuropathy of early childhood onset. The R364W mutation has been reported in five kindreds with an early-onset autosomal dominant severe axonal neuropathy, and associated with variable optic atrophy and vocal cord paresis. We describe the clinical phenotype of a pedigree with the R364W mutation.

    Methods: We describe the clinical and electrophysiological features of a severe early-onset axonal neuropathy in a 53 year old woman and her 24 year old daughter with the R364W mutation.

    Results: Both patients developed gait abnormalities at age three. Features include severe length dependent weakness and wasting, areflexia, optic atrophy and vocal cord paresis. Progression over time to severe disability has occurred in both patients.

    Conclusions: The R364W mutation in the MFN2 gene is associated with a severe early-onset axonal neuropathy with variable additional features of optic atrophy and vocal cord paresis.