The online version of this article (doi:10.1186/1866-1955-6-20) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests.
All authors have been involved in drafting or revising the manuscript, have given final approval, and agree to be accountable for all aspects of the work involved. Each author's individual participation is outlined below. JLN and AKP did the conceptualization and design of the study and acquisition, analysis, and interpretation of the data. H-SL did the statistical analysis of the data. SAS, KJM, WEK, SG, JOB, LMB, and KB did the acquisition and interpretation of the data. DGG and JBL did the conceptualization and design of the study and acquisition and interpretation of the data.
Early development appears normal in Rett syndrome (OMIM #312750) and may be more apparent than real. A major purpose of the Rett Syndrome (RTT) Natural History Study (NHS) was to examine achievement of developmental skills or abilities in classic and atypical RTT and assess phenotype-genotype relations in classic RTT.
Developmental skills in four realms, gross and fine motor, and receptive and expressive communication from initial enrollment and longitudinal assessments for up to 7 years, were assessed from 542 females meeting criteria for classic RTT and 96 females with atypical RTT divided into two groups: 50 with better and 46 with poorer functional scores. Data were analyzed for age at acquisition and loss of developmental features and for phenotype-genotype effects. Acquired, lost, and retained skills were compared between classic RTT and atypical RTT with better or poorer functional scores using Fisher's Exact test. To examine if the mean total score from the Motor Behavioral Assessment during follow-up differed for acquiring a skill, we used a generalized estimating equation assuming compound symmetry correlation structure within a subject. A general linear model was used to examine whether the mean age of acquisition or loss of a developmental skill differed by mutation type. P values <0.05 were considered significant and were two-sided without adjustment for multiple testing. Statistical analyses utilized SAS 9.3 (SAS Institute, Cary, NC, USA).
Early developmental skills or abilities were often acquired albeit later than normal. More complex motor and communication acquisitions were delayed or absent. Clinical severity was less in those achieving the respective skill. Individuals with R133C, R294X, and R306C point mutations and 3′ truncations tended to have better developmental outcomes.
Early developmental skills were acquired by many, but clear differences from normal emerged, particularly in skills expected after age 6 months. When comparing clinical severity, greater acquisition of specific skills was associated with specific mutations, confirming the impression that these mutations confer milder developmental abnormalities. These data may serve for planning and interpretation of early intervention studies in RTT.
This NHS study, clinicaltrials.gov (NCT00296764), represents the largest group of RTT participants assessed repeatedly by direct examination.
Additional file 1: Supplemental table. (DOCX 16 KB)11689_2014_76_MOESM1_ESM.docx
Additional file 2: Inverse Kaplan-Meier graphs for nine acquired developmental skills (A. Sitting, B. Pull to stand, C. Walking, D. Transfer, E. Pincer grasp, F. Quiet to Voice, G. Inhibit to No, H. Babbling, I. Single words). (DOCX 1 MB)11689_2014_76_MOESM2_ESM.docx
Additional file 3: Kaplan-Meier graphs for twelve lost developmental skills A. Sitting, B. Pull to stand, C. Walking, D. Transfer, E. Pincer grasp, F. Reaching, G. Inhibit to ‘No’, H. Babbling, I. Single words, J. Social smile, K. Fix and follow, L. Quiet to voice.(DOCX 1 MB)11689_2014_76_MOESM3_ESM.docx
Authors’ original file for figure 111689_2014_76_MOESM4_ESM.tif
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- Developmental delay in Rett syndrome: data from the natural history study
Jeffrey L Neul
Jane B Lane
Judy O Barrish
Lauren McNair Baggett
Steven A Skinner
Kathleen J Motil
Daniel G Glaze
Walter E Kaufmann
Alan K Percy
- BioMed Central
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