TY - JOUR
T1 - Developmental delay in Rett syndrome
T2 - Data from the natural history study
AU - Neul, Jeffrey L.
AU - Lane, Jane B.
AU - Lee, Hye Seung
AU - Geerts, Suzanne
AU - Barrish, Judy O.
AU - Annese, Fran
AU - Baggett, Lauren Mc Nair
AU - Barnes, Katherine
AU - Skinner, Steven A.
AU - Motil, Kathleen J.
AU - Glaze, Daniel G.
AU - Kaufmann, Walter E.
AU - Percy, Alan K.
N1 - Funding Information:
This study was supported by NIH U54 grants RR019478 and HD061222, Office of Rare Disease Research, and IDDRC grant HD38985, funds from the International Rett Syndrome Foundation and the Civitan International Research Center. The Rett Syndrome Natural History Study (U54 HD061222) is a part of the National Institutes of Health (NIH) Rare Disease Clinical Research Network (RDCRN), supported through collaboration between the NIH Office of Rare Diseases Research (ORDR) at the National Center for Advancing Translational Science (NCATS), and the Eunice Kennedy Shriver Child Health and Human Development Institute (NICHD). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors report no conflicts of interest. The authors acknowledge the gracious participation and provision of information by the families of the reported participants. Dr. Mary Lou Oster-Granite, Health Scientist Administrator at NICHD, provided invaluable guidance, support, and encouragement for this Rare Disease initiative.
Publisher Copyright:
© 2014 Neul et al.; licensee BioMed Central Ltd.
PY - 2014/7/22
Y1 - 2014/7/22
N2 - Background: 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. Methods: 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). Results: 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. Conclusions: 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. Trial registration: This NHS study, clinicaltrials.gov (NCT00296764), represents the largest group of RTT participants assessed repeatedly by direct examination.
AB - Background: 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. Methods: 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). Results: 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. Conclusions: 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. Trial registration: This NHS study, clinicaltrials.gov (NCT00296764), represents the largest group of RTT participants assessed repeatedly by direct examination.
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U2 - 10.1186/1866-1955-6-20
DO - 10.1186/1866-1955-6-20
M3 - Article
C2 - 25071871
AN - SCOPUS:84952877388
SN - 1866-1947
VL - 6
JO - Journal of Neurodevelopmental Disorders
JF - Journal of Neurodevelopmental Disorders
IS - 1
M1 - 20
ER -