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The Cerebellum

, Volume 17, Issue 4, pp 489–493 | Cite as

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

  • Tommaso Schirinzi
  • Federica Graziola
  • Francesco Nicita
  • Lorena Travaglini
  • Fabrizia Stregapede
  • Massimiliano Valeriani
  • Paolo Curatolo
  • Enrico Bertini
  • Federico Vigevano
  • Alessandro Capuano
Short Report

Abstract

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

ATP1A3 Ataxia Cerebellum Rapid-onset dystonia-parkinsonism AHC 

Notes

Compliance with Ethical Standards

All the procedures described in the text have been conducted in accordance with ethical principles.

Conflict of Interest

The authors declare that they have no conflict of interests.

Supplementary material

12311_2018_920_MOESM1_ESM.docx (62 kb)
ESM 1 (DOCX 62 kb)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Tommaso Schirinzi
    • 1
    • 2
  • Federica Graziola
    • 1
    • 3
  • Francesco Nicita
    • 1
  • Lorena Travaglini
    • 1
  • Fabrizia Stregapede
    • 1
  • Massimiliano Valeriani
    • 1
  • Paolo Curatolo
    • 3
  • Enrico Bertini
    • 1
  • Federico Vigevano
    • 1
  • Alessandro Capuano
    • 1
  1. 1.Department of NeurosciencesBambino Gesù Children’s Hospital, IRCCSRomeItaly
  2. 2.Department of Systems MedicineUniversity of Rome Tor VergataRomeItaly
  3. 3.Child Neurology and Psychiatry UnitUniversity of Rome Tor VergataRomeItaly

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