title: Clinical Course of Six Children With GNAO1 Mutations Causing a Severe and Distinctive Movement Disorder.
abstract: Mutations in GNAO1 have been described in 11 patients to date. Although most of these individuals had epileptic encephalopathy, four patients had a severe movement disorder as the prominent feature. We describe the largest series of patients with de novoGNAO1 mutations who have severe chorea, developmental delay, and hypotonia in the absence of epilepsy.
  
  
  
  Six patients with recurrent missense mutations in GNAO1 as detected by whole exome sequencing were identified at three institutions. We describe the presentation, clinical course, and response to treatment of these patients.
  
  
  
  All six patients exhibited global developmental delay and hypotonia from infancy. Chorea developed by age four years in all but one patient, who developed chorea at 14 years. Treatments with neuroleptics and tetrabenazine were most effective in the baseline management of chorea. The chorea became gradually progressive and marked by episodes of severe, refractory ballismus requiring intensive care unit admissions in four of six patients. Exacerbations indirectly led to the death of two patients.
  
  
  
  Patients with GNAO1 mutations can present with a severe, progressive movement disorder in the absence of epilepsy. Exacerbations may be refractory to treatment and can result in life-threatening secondary complications. Early and aggressive treatment of these exacerbations with direct admission to intensive care units for treatment with anesthetic drips may prevent some secondary complications. However the chorea and ballismus can be refractory to maximum medical therapy.
authors.affiliation: Department of Pediatrics, Stanford University, Stanford, California. Electronic address: Amitha@stanford.edu.
authors.forename: Amitha L
authors.initials: AL
authors.lastname: Ananth
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, California; Department of Pediatrics, University of California San Francisco, San Francisco, California. Electronic address: amy.viehoever@UCSF.edu.
authors.forename: Amy
authors.initials: A
authors.lastname: Robichaux-Viehoever
authors.affiliation: Department of Neurology, Washington University in St. Louis School of Medicine, St. Louis, Missouri.
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Department of Pediatrics, Stanford University, Stanford, California; Department of Genetics, Stanford University, Stanford, California.
authors.forename: Andrea
authors.initials: A
authors.lastname: Hanson-Kahn
authors.affiliation: Department of Pediatrics, Stanford University, Stanford, California.
authors.forename: Rachel
authors.initials: R
authors.lastname: Cox
authors.affiliation: Department of Pediatrics, Stanford University, Stanford, California.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Enns
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, California; Department of Pediatrics, University of California San Francisco, San Francisco, California.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Strober
authors.affiliation: Department of Pediatrics, Washington University in St. Louis School of Medicine, St. Louis, Missouri.
authors.forename: Marcia
authors.initials: M
authors.lastname: Willing
authors.affiliation: Department of Neurology, Washington University in St. Louis School of Medicine, St. Louis, Missouri; Department of Pediatrics, Washington University in St. Louis School of Medicine, St. Louis, Missouri; Department of Anatomy and Neurobiology, Washington University in St. Louis School of Medicine, St. Louis, Missouri; Department of Radiology, Washington University in St. Louis School of Medicine, St. Louis, Missouri; Department of Psychiatry, Washington University in St. Louis School of Medicine, St. Louis, Missouri.
authors.forename: Bradley L
authors.initials: BL
authors.lastname: Schlaggar
authors.affiliation: Department of Neurology, University of California San Francisco, San Francisco, California; Department of Pediatrics, University of California San Francisco, San Francisco, California.
authors.forename: Yvonne W
authors.initials: YW
authors.lastname: Wu
authors.affiliation: Department of Pediatrics, Stanford University, Stanford, California.
authors.forename: Jonathan A
authors.initials: JA
authors.lastname: Bernstein
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D018450:Disease Progression; D017809:Fatal Outcome; D005260:Female; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000235:genetics*; D006801:Humans; D008297:Male; D009069:Movement Disorders / Q000188:drug therapy / Q000235:genetics* / Q000503:physiopathology
chemical_list: C584143:GNAO1 protein, human; D019206:GTP-Binding Protein alpha Subunits, Gi-Go
keywords: GNAO1; ballismus; chorea; movement disorder; whole exome sequencing