Recurrent GNAO1 Mutations Associated With Developmental Delay and a Movement Disorder

J Child Neurol. 2016 Dec;31(14):1598-1601. doi: 10.1177/0883073816666474. Epub 2016 Sep 12.


In 2 unrelated patients with axial hypotonia, developmental delay and a hyperkinetic movement disorder, a missense mutation was found in codon 209 of the GNAO1 gene. From the still scarce literature on GNAO1 mutations, a clear genotype-phenotype correlation emerged. From the 26 patients reported thus far, 12 patients had epileptic encephalopathy, and 14 had a developmental delay and a hyperkinetic movement disorder. All but 1 of the latter patients had missense mutations in GNAO1 codon 209 or 246, which thus appear to be mutation hotspots. At least 2 sibling pairs showed that the recurrence risk after 1 affected child with a GNAO1 mutation might be relatively high (5-15%), due to apparent gonadal mosaicism in the parents.

Keywords: GNAO1; chorea; developmental delay; dystonia; epileptic encephalopathy.

Publication types

  • Case Reports

MeSH terms

  • Child, Preschool
  • Developmental Disabilities / genetics*
  • Developmental Disabilities / physiopathology
  • GTP-Binding Protein alpha Subunits, Gi-Go / genetics*
  • Genetic Association Studies
  • Humans
  • Male
  • Movement Disorders / genetics*
  • Movement Disorders / physiopathology
  • Mutation, Missense*
  • Siblings


  • GNAO1 protein, human
  • GTP-Binding Protein alpha Subunits, Gi-Go