title: The expanding spectrum of neurological phenotypes in children with ATP1A3 mutations, Alternating Hemiplegia of Childhood, Rapid-onset Dystonia-Parkinsonism, CAPOS and beyond.
abstract: BACKGROUND
  ATP1A3 mutations have now been recognized in infants and children presenting with a diverse group of neurological phenotypes, including Rapid-onset Dystonia-Parkinsonism (RDP), Alternating Hemiplegia of Childhood (AHC), and most recently, Cerebellar ataxia, Areflexia, Pes cavus, Optic atrophy, and Sensorineural hearing loss (CAPOS) syndrome.
  
  
  METHODS
  Existing literature on ATP1A3-related disorders in the pediatric population were reviewed, with attention to clinical features and associated genotypes among those with RDP, AHC, or CAPOS syndrome phenotypes.
  
  
  RESULTS
  While classically defined phenotypes associated with AHC, RDP, and CAPOS syndromes are distinct, common elements among ATP1A3-related neurological disorders include characteristic episodic neurological symptoms and signs that vary in severity, duration, and frequency of occurrence. Affected children typically present in the context of an acute onset of paroxysmal, episodic neurological symptoms ranging from oculomotor abnormalities, hypotonia, paralysis, dystonia, ataxia, seizure-like episodes, or encephalopathy. Neurodevelopmental delays or persistence of dystonia, chorea, or ataxia after resolution of an initial episode are common, providing important clues for diagnosis.
  
  
  CONCLUSIONS
  The phenotypic spectrum of ATP1A3-related neurological disorders continues to expand beyond the distinct yet overlapping phenotypes in patients with AHC, RDP, and CAPOS syndromes. ATP1A3 mutation analysis is appropriate to consider in the diagnostic algorithm for any child presenting with episodic or fluctuating ataxia, weakness or dystonia whether they manifest persistence of neurological symptoms between episodes. Additional work is needed to better identify and classify affected patients and develop targeted treatment approaches.
authors.affiliation: Division of Pediatric Neurology, Departments of Pediatrics and Neurology, University of Utah School of Medicine, Salt Lake City, Utah; Department of Neurology, Pediatric Motor Disorders Research Program, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Sweney
authors.affiliation: Department of Neurology, Pediatric Motor Disorders Research Program, University of Utah School of Medicine, Salt Lake City, Utah.
authors.forename: Tara M
authors.initials: TM
authors.lastname: Newcomb
authors.affiliation: Department of Neurology, Pediatric Motor Disorders Research Program, University of Utah School of Medicine, Salt Lake City, Utah. Electronic address: swoboda@genetics.utah.edu.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Swoboda
mesh_terms: D000818:Animals; D002524:Cerebellar Ataxia / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D002648:Child; D003937:Diagnosis, Differential; D020821:Dystonic Disorders / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D005532:Foot Deformities, Congenital / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D006319:Hearing Loss, Sensorineural / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D006429:Hemiplegia / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D006801:Humans; D009154:Mutation; D009896:Optic Atrophy / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology / Q000628:therapy; D010641:Phenotype; D012021:Reflex, Abnormal / Q000235:genetics*; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics*
chemical_list: C488756:ATP1A3 protein, human; D000254:Sodium-Potassium-Exchanging ATPase
keywords: ATP1A3; CAPOS syndrome; alternating hemiplegia of childhood; ataxia; dystonia; hemiplegia; rapid-onset dystonia-Parkinsonism; sodium potassium ATPases