title: Profiling scoliosis in Rett syndrome.
abstract: To understand scoliosis, related comorbidities, and phenotype-genotype correlations in individuals with Rett syndrome (RTT), the Rare Disease Clinical Research Network database for RTT was probed. Clinical evaluations included a detailed history and physical examination, comprehensive anthropometric measurements, and two quantitative measures of clinical status, Clinical Severity Scale (CSS) and motor-behavioral analysis (MBA). All data were exported to the Data Technology Coordinating Center (DTCC) at the University of South Florida. Scoliosis assessment was based on direct examination and curvature measurements by radiography (Cobb angle). Statistical analyses included univariate and multiple logistic regression models, adjusting for age at enrollment or mutation type. Scoliosis data were available from 554 classic RTT participants, mean age = 10 y (0-57 y). Scoliosis was noted in 292 (53%); mean age = 15 y with scoliosis and 6 y without. Using multiple regression analysis, MBA severity score, later acquisition, loss or absent walking, and constipation were associated with scoliosis. Two common methyl-CpG-binding protein 2 (MECP2) mutations, R294X and R306C, had reduced risk for scoliosis. These findings corroborated previous reports on scoliosis and extended understanding of comorbidities, clinical severity, and relative risk reduction for specific mutations. Clinical trial design should account for scoliosis and related factors judiciously.
authors.affiliation: Department of Pediatrics, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA. apercy@uab.edu
authors.forename: Alan K
authors.initials: AK
authors.lastname: Percy
authors.forename: Hye-Seung
authors.initials: HS
authors.lastname: Lee
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Neul
authors.forename: Jane B
authors.initials: JB
authors.lastname: Lane
authors.forename: Steven A
authors.initials: SA
authors.lastname: Skinner
authors.forename: Suzanne P
authors.initials: SP
authors.lastname: Geerts
authors.forename: Fran
authors.initials: F
authors.lastname: Annese
authors.forename: Joy
authors.initials: J
authors.lastname: Graham
authors.forename: Lauren
authors.initials: L
authors.lastname: McNair
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Motil
authors.forename: Judy O
authors.initials: JO
authors.lastname: Barrish
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Glaze
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D012044:Regression Analysis; D015518:Rett Syndrome / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D012600:Scoliosis / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D051783:Methyl-CpG-Binding Protein 2