CAOS-Episodic Cerebellar Ataxia, Areflexia, Optic Atrophy, and Sensorineural Hearing Loss

Gali Heimer, Yair Sadaka, Lori Israelian, Ariel Feiglin, Alessandra Ruggieri, Christian R. Marshall, Stephen W. Scherer, Esther Ganelin-Cohen, Dina Marek-Yagel, Michal Tzadok, Andreea Nissenkorn, Yair Anikster, Berge A. Minassian, Bruria Ben Zeev

Research output: Contribution to journalArticle

27 Scopus citations

Abstract

We describe the molecular basis of a distinctive syndrome characterized by infantile stress-induced episodic weakness, ataxia, and sensorineural hearing loss, with permanent areflexia and optic nerve pallor. Whole exome sequencing identified a deleterious heterozygous c.2452 G>A, p.(E818K) variant in the ATP1A3 gene and structural analysis predicted its protein-destabilizing effect. This variant has not been reported in context with rapid-onset dystonia parkinsonism and alternating hemiplegia of childhood, the 2 main diseases associated with ATP1A3. The clinical presentation in the family described here differs categorically from these diseases in age of onset, clinical course, cerebellar over extrapyramidal movement disorder predominance, and peripheral nervous system involvement. While this paper was in review, a highly resembling phenotype was reported in additional patients carrying the same c.2452 G>A variant. Our findings substantiate this variant as the cause of a unique inherited autosomal dominant neurologic syndrome that constitutes a third allelic disease of the ATP1A3 gene.

Original languageEnglish (US)
Pages (from-to)1749-1756
Number of pages8
JournalJournal of Child Neurology
Volume30
Issue number13
DOIs
StatePublished - Jan 1 2015

Keywords

  • alternating hemiplegia of childhood
  • CAPOS
  • deafness
  • intermittent weakness
  • rapid-onset dystonia parkinsonism

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Clinical Neurology

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    Heimer, G., Sadaka, Y., Israelian, L., Feiglin, A., Ruggieri, A., Marshall, C. R., Scherer, S. W., Ganelin-Cohen, E., Marek-Yagel, D., Tzadok, M., Nissenkorn, A., Anikster, Y., Minassian, B. A., & Zeev, B. B. (2015). CAOS-Episodic Cerebellar Ataxia, Areflexia, Optic Atrophy, and Sensorineural Hearing Loss. Journal of Child Neurology, 30(13), 1749-1756. https://doi.org/10.1177/0883073815579708