Intermediate Phenotypes of &lt;i&gt;ATP1A3&lt;/i&gt; Mutations: Phenotype–Genotype Correlations

Pichet Termsarasab,Amy C Yang,Steven J Frucht

doi:10.5334/tohm.255

Abstract

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.

Highlights

Heterozygous ATP1A3 mutations were initially described in rapid-onset dystonia–parkinsonism (RDP or DYT12) (MIM 128235).[1]
Advances in genetic techniques led to the subsequent discovery that abnormalities in the same gene were responsible for some forms of alternating hemiplegia of childhood (AHC) (MIM 614820),[2] and the CAPOS syndrome (Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy and Sensorineural hearing loss) (MIM 601338).[3]
Clinical features of each patient were classified according to whether they were more compatible with alternating hemiplegia vs. rapidonset dystonia–parkinsonism. “+” sign indicates the presence of the features in each patient. 1Features that are seen in the videos

Summary

Case Reports

Frucht[1 1] Movement Disorder Division, Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, USA, 2 Department of Genetics and Genomic

Introduction

Case report

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