Diffuse hypomyelination is not obligate for POLR3-related disorders

Neurology. 2016 Apr 26;86(17):1622-6. doi: 10.1212/WNL.0000000000002612. Epub 2016 Mar 30.


Objective: To report atypical MRI patterns associated with POLR3A and POLR3B mutations.

Methods: This was a multicenter retrospective study to collect neuroradiologic, clinical, and molecular data of patients with mutations in POLR3A and POLR3B without the classic MRI phenotype, i.e., diffuse hypomyelination associated with relative T2 hypointensity of the ventrolateral thalamus, globus pallidus, optic radiation, corticospinal tract at the level of the internal capsule, and dentate nucleus, cerebellar atrophy, and thinning of the corpus callosum.

Results: Eight patients were identified: 6 carried mutations in POLR3A and 2 in POLR3B. We identified 2 novel MRI patterns: 4 participants presented a selective involvement of the corticospinal tracts, specifically at the level of the posterior limbs of the internal capsules; 4 patients presented moderate to severe cerebellar atrophy. Incomplete hypomyelination was observed in 5 participants.

Conclusion: Diffuse hypomyelination is not an obligatory feature of POLR3-related disorders. Two distinct patterns, selective involvement of the corticospinal tracts and cerebellar atrophy, are added to the MRI presentation of POLR3-related disorders.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Atrophy
  • Brain / diagnostic imaging*
  • Child
  • Child, Preschool
  • Cross-Sectional Studies
  • Hereditary Central Nervous System Demyelinating Diseases / diagnostic imaging*
  • Hereditary Central Nervous System Demyelinating Diseases / genetics*
  • Humans
  • Magnetic Resonance Imaging
  • Mutation
  • Myelin Sheath
  • Phenotype
  • Pyramidal Tracts / diagnostic imaging
  • RNA Polymerase III / genetics*
  • Retrospective Studies
  • Young Adult


  • POLR3A protein, human
  • POLR3B protein, human
  • RNA Polymerase III