Intermediate Phenotypes of ATP1A3 Mutations: Phenotype-Genotype Correlations

Tremor Other Hyperkinet Mov (N Y). 2015 Sep 16;5:336. doi: 10.7916/D8MG7NS8. eCollection 2015.


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.