Early-onset cerebellar ataxia in a patient with CMT2A2

Cold Spring Harb Mol Case Stud. 2020 Jun 12;6(3):a005108. doi: 10.1101/mcs.a005108. Print 2020 Jun.


A 9-yr 8-mo-old right-handed female presented with a history of gait difficulties, which first became apparent at age 9 mo of age, along with slurred speech and hand tremors while holding a tray. Her past medical history was significant for global developmental delay, and she was attending fourth grade special education classes. On examination, she had an ataxic gait, dysarthria, absent deep tendon reflexes, and flexor plantar responses. There were no signs of optic atrophy or hearing loss. Nerve conduction studies were consistent with an axonal neuropathy. A fascicular sural nerve biopsy showed a marked decrease of myelinated fibers larger than 6 µm in diameter as compared with an age-matched control. By electron microscopy, clusters of degenerating axonal mitochondria in both myelinated and unmyelinated fibers were frequently found. Whole-exome sequencing revealed a heterozygous c.314C > T (p.Thr105Met) missense variant in MFN2 in the patient but not in her mother. The father was unavailable for testing. The phenotypes with MFN2 variants can be quite variable, including intellectual disability, optic atrophy, auditory impairment, spinal atrophy with or without hydromyelia, and hydrocephalus. We report here that early onset ataxia with intellectual disability can also be associated with MFN2-related Charcot-Marie-Tooth, Type 2A2A diagnosis, the most common type of autosomal dominant axonal neuropathy.

Keywords: progressive cerebellar ataxia; severe global developmental delay.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Axons / ultrastructure
  • Biomarkers
  • Charcot-Marie-Tooth Disease / diagnosis*
  • Charcot-Marie-Tooth Disease / genetics*
  • Chromosome Mapping
  • Exome Sequencing
  • Family
  • Female
  • GTP Phosphohydrolases / genetics
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Genetic Testing
  • Humans
  • Infant
  • Mitochondria / genetics
  • Mitochondria / ultrastructure
  • Mitochondrial Proteins / genetics
  • Mutation
  • Phenotype*
  • Pregnancy
  • Spinocerebellar Degenerations / diagnosis*
  • Spinocerebellar Degenerations / genetics*
  • Symptom Assessment


  • Biomarkers
  • Mitochondrial Proteins
  • GTP Phosphohydrolases
  • MFN2 protein, human

Supplementary concepts

  • Charcot-Marie-Tooth Disease, Axonal, Type 2A2