title: Genotype and early development in Rett syndrome: the value of international data.
abstract: BACKGROUND
  Rett syndrome is a neurodevelopmental disorder mostly affecting females and caused by mutations in the MECP2 gene. Originally the syndrome was characterised as having a normal prenatal and perinatal period with later regression. Previous work has speculated that the girl with Rett syndrome may not be normal at birth.
  
  
  OBJECTIVE
  to examine whether early development between birth and ten months varies by genotype in Rett syndrome.
  
  
  METHODS
  cases were sourced from two databases, the Australian Rett Syndrome Database (est. 1993) and the newly formed InterRett - IRSA Rett Phenotype Database. Data available on 320 cases included information provided by parents on perinatal problems, early developmental behaviour and mobility. Problem scores, mobility scores and a total composite score for each mutation were generated and compared.
  
  
  RESULTS
  overall, 58% of respondents noted unusual behaviour during the first six months and 70.6% from the period between 6 and 10 months of life. Statistically significant differences were detected between some of the common mutations. Infants with R294X (P=0.05) and R133C (P=0.03) were less likely than those with R255X to have problems in the perinatal period. The most severe profile overall for early development was associated with mutations R255X and R270X.
  
  
  CONCLUSIONS
  This is the largest study to date examining the effects of individual mutations in Rett syndrome. With the ongoing case ascertainment and expansion of InterRett, sample size will increase rapidly and provide improved statistical power for future analyses. Results from this study will contribute to understanding the mechanism of early development in Rett syndrome and determining if and at which time(s) early intervention might be feasible.
authors.affiliation: Telethon Institute for Child Health Research, Centre for Child Health Research, The University of Western Australia, Perth, Western Australia. hleonard@ichr.uwa.edu.au
authors.forename: Helen
authors.initials: H
authors.lastname: Leonard
authors.forename: Hannah
authors.initials: H
authors.lastname: Moore
authors.forename: Mary
authors.initials: M
authors.lastname: Carey
authors.forename: Susan
authors.initials: S
authors.lastname: Fyfe
authors.forename: Sonj
authors.initials: S
authors.lastname: Hall
authors.forename: Laila
authors.initials: L
authors.lastname: Robertson
authors.forename: Xi Ru
authors.initials: XR
authors.lastname: Wu
authors.forename: Xinhua
authors.initials: X
authors.lastname: Bao
authors.forename: Hong
authors.initials: H
authors.lastname: Pan
authors.forename: John
authors.initials: J
authors.lastname: Christodoulou
authors.forename: Sarah
authors.initials: S
authors.lastname: Williamson
authors.forename: Nick de
authors.initials: Nd
authors.lastname: Klerk
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004252:DNA Mutational Analysis; D016208:Databases, Factual; D005192:Family Health; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D038622:Internationality; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D009154:Mutation; D012189:Retrospective Studies; D015518:Rett Syndrome / Q000453:epidemiology / Q000235:genetics / Q000503:physiopathology
chemical_list: D051783:Methyl-CpG-Binding Protein 2