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.
Keywords
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Article info
Publication history
Published online: August 29, 2014
Accepted:
August 23,
2014
Received:
May 31,
2014
Footnotes
Funding provided by National Institutes of Health/National Institute of Child Health and Human Development: U54HD061222
The authors report no conflicts.
Clinical Trial #: NCT00296764.
Identification
Copyright
© 2014 Elsevier Inc. Published by Elsevier Inc. All rights reserved.
