title: Pubertal development in Rett syndrome deviates from typical females.
abstract: BACKGROUND
  Rett syndrome is a unique neurodevelopmental disorder, affecting approximately one in 10,000 live female births, most experiencing reduced growth. We characterized pubertal trajectories in females with Rett syndrome. We hypothesized that pubertal trajectory deviates from the general female population with early pubertal onset and delayed menarche.
  
  
  METHODS
  Participants were individuals enrolled in the Rett Syndrome Natural History Study with clinical diagnosis of Rett syndrome or mutations in MECP2. Intervals to thelarche, adrenarche, and menarche were assessed by survival analysis; body mass index, mutation type, clinical severity, and pubertal milestone relationships were assessed by log-likelihood test; pathway synchrony (relationship between thelarche, adrenarche, and menarche) was assessed by chi-squared analysis.
  
  
  RESULTS
  Compared with the general female population, more than 25% initiated puberty early, yet entered menarche later (median age 13.0 years). A total of 19% experienced delayed menarche. Median length of puberty, from thelarche to menarche, was 3.9 years. Higher body mass index correlated with earlier thelarche and adrenarche but not menarche; milder mutations correlated with earlier menarche; and milder clinical presentation correlated with earlier thelarche and menarche. Fifty-two percent entered puberty in synchrony, but different from the general population, 15% led with thelarche and 32% with adrenarche.
  
  
  CONCLUSIONS
  Pubertal trajectories in Rett syndrome differ from general population, entering puberty early and reaching menarche later. Body mass index affects pubertal timing, but the relationship between specific mutations, clinical presentation, and underlying neuroendocrine pathology is less clear.
authors.affiliation: School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: John T
authors.initials: JT
authors.lastname: Killian
authors.affiliation: Civitan International Research Center, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Jane B
authors.initials: JB
authors.lastname: Lane
authors.affiliation: School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Gary R
authors.initials: GR
authors.lastname: Cutter
authors.affiliation: Greenwood Genetic Center, Greenwood, South Carolina.
authors.forename: Steven A
authors.initials: SA
authors.lastname: Skinner
authors.affiliation: Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Walter E
authors.initials: WE
authors.lastname: Kaufmann
authors.affiliation: Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Daniel C
authors.initials: DC
authors.lastname: Tarquinio
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Glaze
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Kathleen J
authors.initials: KJ
authors.lastname: Motil
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, Texas.
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Neul
authors.affiliation: Civitan International Research Center, University of Alabama at Birmingham, Birmingham, Alabama. Electronic address: apercy@uab.edu.
authors.forename: Alan K
authors.initials: AK
authors.lastname: Percy
mesh_terms: D000293:Adolescent; D002648:Child; D005260:Female; D006801:Humans; D008572:Menarche / Q000235:genetics / Q000502:physiology; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics; D011627:Puberty / Q000235:genetics / Q000502:physiology*; D015518:Rett Syndrome / Q000235:genetics / Q000503:physiopathology*; D013997:Time Factors
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2
keywords: Body mass index; MECP2 mutations; Menarche; Puberty; Rett syndrome; neurodevelopmental disorder