title: Scoliosis in Rett Syndrome: Progression, Comorbidities, and Predictors.
abstract: Scoliosis is prominent in Rett syndrome (RTT). Following the prior report from the US Natural History Study, the onset and progression of severe scoliosis (≥40° Cobb angle) and surgery were examined regarding functional capabilities and specific genotypes, addressing the hypothesis that abnormal muscle tone, poor oral feeding, puberty, and delays or absence of sitting balance and ambulation may be responsible for greater risk in RTT.
  
  
  
  The multicenter RTT Natural History Study gathered longitudinal data for classic RTT, including mutation type, scoliosis, muscle tone, sitting, ambulation, hand function, and feeding. Cox regression models were used to examine the association between scoliosis and functional characteristics. All analyses utilized SAS 9.4; two-sided P values of <0.05 were considered significant.
  
  
  
  A total of 913 females with classic RTT were included. Scoliosis frequency and severity increased with age. Severe scoliosis was found in 251 participants (27%), 113 of whom developed severe scoliosis during the follow-up assessments; 168 (18%) had surgical correction. Severe MECP2 mutations (R106W, R168X, R255X, R270X, and large deletions) showed a higher proportion of scoliosis. Individuals developing severe scoliosis or requiring surgery were less likely to sit, ambulate, or use their hands and were more likely to have begun puberty. Significant differences were absent for epilepsy rates, sleep problems, or constipation.
  
  
  
  Scoliosis requires vigilance regarding the risk factors noted, particularly specific mutations and the role of puberty and motor abilities. Bracing is recommended for moderate curves and surgery for severe curves in accordance with published guidelines for scoliosis management.
authors.affiliation: University of Alabama at Birmingham, School of Medicine, Birmingham, Alabama.
authors.forename: John T
authors.initials: JT
authors.lastname: Killian
authors.affiliation: University of Alabama at Birmingham, School of Medicine, Birmingham, Alabama; University of Alabama at Birmingham, Civitan International Research Center, Birmingham, Alabama.
authors.forename: Jane B
authors.initials: JB
authors.lastname: Lane
authors.affiliation: Health Informatics Institute, Department of Pediatrics, Morsani College of Medicine, University of South Florida, Tampa, Florida.
authors.forename: Hye-Seung
authors.initials: HS
authors.lastname: Lee
authors.affiliation: Greenwood Genetic Center, Greenwood, South Carolina.
authors.forename: Steve A
authors.initials: SA
authors.lastname: Skinner
authors.affiliation: Greenwood Genetic Center, Greenwood, South Carolina.
authors.forename: Walter E
authors.initials: WE
authors.lastname: Kaufmann
authors.affiliation: Baylor College of Medicine, Houston, Texas.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Glaze
authors.affiliation: University of California San Diego, San Diego, California.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Neul
authors.affiliation: University of Alabama at Birmingham, School of Medicine, Birmingham, Alabama; University of Alabama at Birmingham, Civitan International Research Center, Birmingham, Alabama. Electronic address: apercy@uab.edu.
authors.forename: Alan K
authors.initials: AK
authors.lastname: Percy
mesh_terms: D000293:Adolescent; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D015897:Comorbidity; D018450:Disease Progression; D005260:Female; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D011237:Predictive Value of Tests; D015995:Prevalence; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D015518:Rett Syndrome / Q000150:complications / Q000453:epidemiology / Q000235:genetics; D012600:Scoliosis / Q000453:epidemiology* / Q000209:etiology*; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2
keywords: MECP2 mutations; Rett syndrome; puberty; scoliosis; surgery