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. 2015 Sep 16;5:336.
doi: 10.7916/D8MG7NS8. eCollection 2015.

Intermediate Phenotypes of ATP1A3 Mutations: Phenotype-Genotype Correlations

Free PMC article

Intermediate Phenotypes of ATP1A3 Mutations: Phenotype-Genotype Correlations

Pichet Termsarasab et al. Tremor Other Hyperkinet Mov (N Y). .
Free PMC article


Background: ATP1A3-related disorders include rapid-onset dystonia-parkinsonism (RDP or DYT12), alternating hemiplegia of childhood (AHC), and CAPOS syndrome (Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy, and Sensorineural hearing loss).

Case report: We report two cases with intermediate forms between RDP and AHC. Patient 1 initially presented with the AHC phenotype, but the RDP phenotype emerged at age 14 years. The second patient presented with levodopa-responsive paroxysmal oculogyria, a finding never before reported in ATP1A3-related disorders. Genetic testing confirmed heterozygous changes in the ATP1A3 gene in both patients, one of them novel.

Discussion: Intermediate phenotypes of RDP and AHC support the concept that these two disorders are part of a spectrum. We add our cases to the phenotype-genotype correlations of ATP1A3-related disorders.

Keywords: ATP1A3; dystonia; parkinsonism; rapid-onset dystonia–parkinsonism.

Conflict of interest statement

Conflicts of Interest: The authors report no conflict of interest.

Ethics Statement: This study was performed in accordance with the ethical standards detailed in the Declaration of Helsinki. The authors' institutional ethics committee has approved this study and all patients have provided written informed consent.

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    1. de Carvalho Aguiar P, Sweadner KJ, Penniston JT, et al. Mutations in the Na+/K+ -ATPase alpha3 gene ATP1A3 are associated with rapid-onset dystonia parkinsonism. Neuron. 2004;43:169–175. - PubMed
    1. Heinzen EL, Swoboda KJ, Hitomi Y, et al. De novo mutations in ATP1A3 cause alternating hemiplegia of childhood. Nat Genet. 2012;44:1030–1034. - DOI - PMC - PubMed
    1. Demos MK, van Karnebeek CD, Ross CJ, et al. A novel recurrent mutation in ATP1A3 causes CAPOS syndrome. Orphanet J Rare Dis. 2014;9:15. - DOI - PMC - PubMed
    1. Roubergue A, Roze E, Vuillaumier-Barrot S, et al. The multiple faces of the ATP1A3-related dystonic movement disorder. Mov Disord. 2013;28:1457–1459. - DOI - PubMed
    1. Sasaki M, Ishii A, Saito Y, Hirose S. Intermediate form between alternating hemiplegia of childhood and rapid-onset dystonia-parkinsonism. Mov Disord. 2014;29:153–154. - DOI - PubMed