ATP1A3-related disorders: An update

Eur J Paediatr Neurol. 2018 Mar;22(2):257-263. doi: 10.1016/j.ejpn.2017.12.009. Epub 2017 Dec 21.


Alternating Hemiplegia of Childhood (AHC), Rapid-onset Dystonia Parkinsonism (RDP) and CAPOS syndrome (cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss) are three distinct, yet partially overlapping clinical syndromes that have long been thought to be allelic disorders. From 2004 to 2012, both autosomal dominant and de novo mutations in ATP1A3 have been detected in patients affected by these three conditions. Growing evidence suggests that AHC, RDP and CAPOS syndrome are part of a large and continuously expanding clinical spectrum and share some recurrent clinical features, such as abrupt-onset, asymmetric anatomical distribution and the presence of triggering factors, which are highly suggestive of ATP1A3 mutations. In this review, we will highlight the main clinical and genetic features of ATP1A3-related disorders focussing on shared and distinct features that can be helpful in clinical practice to individuate mutation carriers.

Keywords: ATP1A3; Dystonia; Genetics; Movement disorders; Parkinsonism.

Publication types

  • Review

MeSH terms

  • Cerebellar Ataxia / genetics*
  • Child, Preschool
  • Dystonic Disorders / genetics*
  • Female
  • Foot Deformities, Congenital / genetics*
  • Genetic Association Studies
  • Hearing Loss, Sensorineural / genetics*
  • Hemiplegia / genetics*
  • Humans
  • Mutation
  • Optic Atrophy / genetics*
  • Reflex, Abnormal / genetics*
  • Sodium-Potassium-Exchanging ATPase / genetics*


  • ATP1A3 protein, human
  • Sodium-Potassium-Exchanging ATPase

Supplementary concepts

  • Alternating hemiplegia of childhood
  • CAPOS syndrome
  • Dystonia 12