Expanding the Phenotype of Homozygous KCNMA1 Mutations; Dyskinesia, Epilepsy, Intellectual Disability, Cerebellar and Corticospinal Tract Atrophy

Balkan Med J. 2018 Jul 24;35(4):336-339. doi: 10.4274/balkanmedj.2017.0986. Epub 2018 Mar 16.


Background: The KCNMA1 gene encodes the α-subunit of the large conductance, voltage, and calcium-sensitive potassium channel (BK channels) that plays a critical role in neuronal excitability. Heterozygous mutations in KCNMA1 were first illustrated in a large family with generalized epilepsy and paroxysmal nonkinesigenic dyskinesia. Recent research has established homozygous KCNMA1 mutations accountable for the phenotype of cerebellar atrophy, developmental delay, and seizures.

Case report: Here, we report the case of a patient with a novel homozygous truncating mutation in KCNMA1 (p.Arg458Ter) presenting with both the loss- and gain-of-function phenotype with paroxysmal dyskinesia, epilepsy, intellectual delay, and corticospinal–cerebellar tract atrophy.

Conclusion: This report extends the KNCMA1 mutation phenotype with a patient who carries a novel frameshift variant, presenting with both the gain- and loss-of-function phenotypes along with spinal tract involvement as a novel characteristic.

Keywords: Cerebellar atrophy, dyskinesia, epilepsy, KCNMA1, spinal tract atrophy.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Atrophy / genetics
  • Diffusion Tensor Imaging
  • Epilepsy / genetics*
  • Epilepsy / pathology
  • Humans
  • Infant
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / genetics*
  • Large-Conductance Calcium-Activated Potassium Channels
  • Male
  • Mutation*
  • Pedigree
  • Phenotype
  • Pyramidal Tracts / pathology*


  • KCNMA1 protein, human
  • Large-Conductance Calcium-Activated Potassium Channel alpha Subunits
  • Large-Conductance Calcium-Activated Potassium Channels