2015 Articles

Intermediate Phenotypes of ATP1A3 Mutations: Phenotype–Genotype Correlations

Termsarasab, Pichet; Yang, Amy C.; Frucht, Steven J.

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.