title: Early determinants of fractures in Rett syndrome.
abstract: OBJECTIVE
  The goals were to compare the fracture incidence in Rett syndrome with that in the general population and to investigate the impact of genotype, epilepsy, and early motor skills on subsequent fracture incidence in girls and young women with Rett syndrome.
  
  
  METHODS
  The Australian Rett syndrome study, a population-based study operating since 1993, investigated Australian subjects with Rett syndrome born since 1976. The 234 (81.2%) of 288 verified cases in the Australian Rett syndrome database in 2004 whose families had completed follow-up questionnaires and provided information about fracture history were included in the analyses. The main outcomes were fracture incidence in the Rett syndrome population and fracture risk according to genotype, presence of epilepsy, and early motor profile.
  
  
  RESULTS
  Fracture incidence in this cohort was 43.3 episodes per 1000 person-years, nearly 4 times greater than the population rate. Risk was increased specifically in cases with p.R270X mutations and in cases with p.R168X mutations. Having epilepsy also increased fracture risk, even after adjustment for genotype.
  
  
  CONCLUSIONS
  Girls and young women with Rett syndrome are at increased risk of fracture. Those with mutations found previously to be more severe and those with epilepsy have an increased propensity toward fractures. Improved understanding of the risk factors for fracture could contribute to better targeting of interventions to decrease fracture incidence in this vulnerable population.
authors.affiliation: Centre for Child Health Research, University of Western Australia, Telethon Institute for Child Health Research, Perth, Western Australia, 6872.
authors.forename: Jennepher
authors.initials: J
authors.lastname: Downs
authors.forename: Ami
authors.initials: A
authors.lastname: Bebbington
authors.forename: Helen
authors.initials: H
authors.lastname: Woodhead
authors.forename: Peter
authors.initials: P
authors.lastname: Jacoby
authors.forename: Le
authors.initials: L
authors.lastname: Jian
authors.forename: Amanda
authors.initials: A
authors.lastname: Jefferson
authors.forename: Helen
authors.initials: H
authors.lastname: Leonard
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D015519:Bone Density; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D016001:Confidence Intervals; D004252:DNA Mutational Analysis; D002658:Developmental Disabilities / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D050723:Fractures, Bone / Q000453:epidemiology* / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015994:Incidence; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D009154:Mutation; D009517:New South Wales / Q000453:epidemiology; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D012016:Reference Values; D012042:Registries; D012189:Retrospective Studies; D015518:Rett Syndrome / Q000235:genetics* / Q000401:mortality* / Q000503:physiopathology; D018570:Risk Assessment; D012640:Seizures / Q000453:epidemiology / Q000209:etiology; D012720:Severity of Illness Index; D016019:Survival Analysis
chemical_list: D051783:Methyl-CpG-Binding Protein 2