title: Rett syndrome: investigation of nine patients, including PET scan.
abstract: BACKGROUND
  We describe nine females with Rett Syndrome (RS), aged 14 to 26 years. All had had developmental delay before the end of their first year and had subsequently regressed to profound dementia with apraxia, ataxia, irregular respirations and often also seizures.
  
  
  METHODS
  The Revised Gesell developmental assessment and Alpern-Boll Developmental Profile were used in modified form. Volumetric measurements of basal ganglia using MRI were compared with the findings in nine age-matched volunteer females. Positron emission scans with [18F]-6-fluorodopa and [11C]-raclopride were performed under light anesthesia with intravenous Propofol, and the findings were compared with those in healthy control girls. Bidirectional sequencing of the coding regions of the MECP2 gene was investigated in blood samples for mutational analyses.
  
  
  RESULTS
  The RS females functioned at a mental age level ranging from about 4 to 15 months. The scores correlated with height, weight and head circumference. Magnetic resonance scans of basal ganglia showed a significant reduction in the size of the caudate heads and thalami in the Rett cases. Positron emission scans demonstrated that the mean uptake of fluorodopa in RS was reduced by 13.1% in caudate and by 12.5% in putamen as compared to the controls, while dopamine D2 receptor binding was increased significantly by 9.7% in caudate and 9.6% in putamen. Mutations in the coding regions of the MECP2 gene were present in all nine patients. No significant correlation between type and location of mutation and volumetric changes or isotope uptake was demonstrable.
  
  
  CONCLUSIONS
  Our findings suggest a mild presynaptic deficit of nigrostriatal activity in Rett syndrome.
authors.affiliation: Division of Neurology, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Henry G
authors.initials: HG
authors.lastname: Dunn
authors.forename: A Jon
authors.initials: AJ
authors.lastname: Stoessl
authors.forename: Helena H
authors.initials: HH
authors.lastname: Ho
authors.forename: Patrick M
authors.initials: PM
authors.lastname: MacLeod
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Poskitt
authors.forename: Doris J
authors.initials: DJ
authors.lastname: Doudet
authors.forename: Michael
authors.initials: M
authors.lastname: Schulzer
authors.forename: Derek
authors.initials: D
authors.lastname: Blackstock
authors.forename: Teresa
authors.initials: T
authors.lastname: Dobko
authors.forename: Ben
authors.initials: B
authors.lastname: Koop
authors.forename: Giovana V
authors.initials: GV
authors.lastname: de Amorim
mesh_terms: D000293:Adolescent; D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging; D018797:Cell Cycle Proteins; D064447:Checkpoint Kinase 2; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011859:Radiography; D015518:Rett Syndrome / Q000000981:diagnostic imaging* / Q000235:genetics / Q000503:physiopathology*; D029701:Saccharomyces cerevisiae Proteins; D014055:Tomography, Emission-Computed
chemical_list: D018797:Cell Cycle Proteins; D029701:Saccharomyces cerevisiae Proteins; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae