Childhood Rapid-Onset Ataxia: Expanding the Phenotypic Spectrum of ATP1A3 Mutations

Cerebellum. 2018 Aug;17(4):489-493. doi: 10.1007/s12311-018-0920-y.


ATP1A3 mutations are related to a wide spectrum of clinical conditions, including several defined syndromes as rapid-onset dystonia-parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS), together with many other intermediate phenotypes. Ataxia is always more increasingly reported, either as accessory or prominent sign, in ATP1A3-related conditions, being thus considered as a peculiar feature of this spectrum. Here, we report three cases of childhood rapid-onset ataxia due to two different ATP1A3 variants. Interestingly, two patients (mother and son) showed a variant c.2266C>T (p.R756C), while the third carried the c.2452G>A (p.E818K) variant, commonly described in association with CAPOS syndrome. Our report contributes to extent the phenotypic spectrum of ATP1A3 mutations, remarking childhood rapid-onset ataxia as an additional clinical presentation of ATP1A3-related conditions. Finally, we discussed this phenomenology in the light of translational evidence from a RDP animal model.

Keywords: AHC; ATP1A3; Ataxia; Cerebellum; Rapid-onset dystonia-parkinsonism.

Publication types

  • Case Reports

MeSH terms

  • Age of Onset
  • Ataxia / epidemiology
  • Ataxia / genetics*
  • Ataxia / physiopathology
  • Child, Preschool
  • Disease Progression
  • Female
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Mutation*
  • Pedigree
  • Phenotype
  • Sodium-Potassium-Exchanging ATPase / genetics*


  • ATP1A3 protein, human
  • Sodium-Potassium-Exchanging ATPase