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

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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.

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Authors and Affiliations

  1. Department of Neurosciences, Bambino Gesù Children’s Hospital, IRCCS, Piazza Sant’Onofrio 4, 00165, Rome, Italy

    Tommaso Schirinzi, Federica Graziola, Francesco Nicita, Lorena Travaglini, Fabrizia Stregapede, Massimiliano Valeriani, Enrico Bertini, Federico Vigevano & Alessandro Capuano

  2. Department of Systems Medicine, University of Rome Tor Vergata, Rome, Italy

    Tommaso Schirinzi

  3. Child Neurology and Psychiatry Unit, University of Rome Tor Vergata, Rome, Italy

    Federica Graziola & Paolo Curatolo

Authors
  1. Tommaso Schirinzi
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  2. Federica Graziola
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  3. Francesco Nicita
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  4. Lorena Travaglini
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  5. Fabrizia Stregapede
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  6. Massimiliano Valeriani
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  7. Paolo Curatolo
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  8. Enrico Bertini
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  9. Federico Vigevano
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  10. Alessandro Capuano
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Corresponding author

Correspondence to Alessandro Capuano.

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

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The authors declare that they have no conflict of interests.

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Schirinzi, T., Graziola, F., Nicita, F. et al. Childhood Rapid-Onset Ataxia: Expanding the Phenotypic Spectrum of ATP1A3 Mutations. Cerebellum 17, 489–493 (2018). https://doi.org/10.1007/s12311-018-0920-y

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  • DOI: https://doi.org/10.1007/s12311-018-0920-y

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