Histopathology of the Inner Ear in Charcot-Marie-Tooth Syndrome Caused by a Missense Variant (p.Thr65Ala) in the MPZ Gene

Audiol Neurootol. 2018;23(6):326-334. doi: 10.1159/000495176. Epub 2019 Jan 24.


Charcot-Marie-Tooth (CMT) syndrome is a clinically and genetically heterogeneous group of neuropathies affecting both peripheral motor and sensory nerves. Progressive sensorineural hearing loss, vestibular abnormalities, and dysfunction of other cranial nerves have been described. This is the second case report of otopathology in a patient with CMT syndrome. Molecular genetic testing of DNA obtained at autopsy revealed a missense variant in the MPZ gene (p.Thr65Ala), pathogenic for an autosomal-dominant form of CMT1B. The temporal bones were also prepared for light microscopy by hematoxylin and eosin and Gömöri trichome stains, and immunostaining for anti-myelin protein zero. Pathology was consistent with a myelinopathy of the auditory, vestibular, and facial nerves bilaterally. The pathophysiology of cranial nerve dysfunction in CMT is unknown. Findings in the current case suggested, at least in cranial nerves 7 and 8, that a myelinopathy may be causative.

Keywords: Charcot-Marie-Tooth syndrome; Cranial nerves; Histopathology; Myelin protein zero gene; Myelinopathy; Sensorineural hearing loss.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • Alanine / genetics
  • Charcot-Marie-Tooth Disease / genetics*
  • Charcot-Marie-Tooth Disease / pathology*
  • Chromosome Aberrations
  • Cochlear Nerve / pathology*
  • Ear, Inner / innervation*
  • Facial Nerve / pathology
  • Genes, Dominant / genetics
  • Genetic Variation / genetics*
  • Humans
  • Male
  • Mutation, Missense / genetics*
  • Myelin P0 Protein / genetics*
  • Myelin Sheath / pathology
  • Threonine / genetics
  • Vestibular Nerve / pathology
  • Whole Exome Sequencing


  • MPZ protein, human
  • Myelin P0 Protein
  • Threonine
  • Alanine

Supplementary concepts

  • Charcot-Marie-Tooth disease, Type 4C