ATP1A3 mutations in infants: a new rapid-onset dystonia-Parkinsonism phenotype characterized by motor delay and ataxia

Dev Med Child Neurol. 2012 Nov;54(11):1065-7. doi: 10.1111/j.1469-8749.2012.04421.x. Epub 2012 Aug 28.


We report new clinical features of delayed motor development, hypotonia, and ataxia in two young children with mutations (R756H and D923N) in the ATP1A3 gene. In adults, mutations in ATP1A3 cause rapid-onset dystonia-Parkinsonism (RDP, DYT12) with abrupt onset of fixed dystonia. The parents and children were examined and videotaped, and samples were collected for mutation analysis. Case 1 presented with fluctuating spells of hypotonia, dysphagia, mutism, dystonia, and ataxia at 9 months. After three episodes of hypotonia, she developed ataxia, inability to speak or swallow, and eventual seizures. Case 2 presented with hypotonia at 14 months and pre-existing motor delay. At age 4 years, he had episodic slurred speech, followed by ataxia, drooling, and dysarthria. He remains mute. Both children had ATP1A3 gene mutations. To our knowledge, these are the earliest presentations of RDP, both with fluctuating features. Both children were initially misdiagnosed. RDP should be considered in children with discoordinated gait, and speech and swallowing difficulties.

Trial registration: NCT00682513.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adult
  • Ataxia / etiology
  • Ataxia / genetics
  • Developmental Disabilities / etiology
  • Developmental Disabilities / genetics
  • Dystonic Disorders / complications
  • Dystonic Disorders / diagnosis
  • Dystonic Disorders / genetics*
  • Female
  • Humans
  • Infant
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Phenotype*
  • Sodium-Potassium-Exchanging ATPase / genetics*


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

Supplementary concepts

  • Dystonia 12

Associated data