Abstract
To understand scoliosis, related comorbidities, and phenotype-genotype correlations in individuals with Rett syndrome (RTT), the Rare Disease Clinical Research Network database for RTT was probed. Clinical evaluations included a detailed history and physical examination, comprehensive anthropometric measurements, and two quantitative measures of clinical status, Clinical Severity Scale (CSS) and motor-behavioral analysis (MBA). All data were exported to the Data Technology Coordinating Center (DTCC) at the University of South Florida. Scoliosis assessment was based on direct examination and curvature measurements by radiography (Cobb angle). Statistical analyses included univariate and multiple logistic regression models, adjusting for age at enrollment or mutation type. Scoliosis data were available from 554 classic RTT participants, mean age = 10 y (0–57 y). Scoliosis was noted in 292 (53%); mean age = 15 y with scoliosis and 6 y without. Using multiple regression analysis, MBA severity score, later acquisition, loss or absent walking, and constipation were associated with scoliosis. Two common methyl-CpG-binding protein 2 (MECP2) mutations, R294X and R306C, had reduced risk for scoliosis. These findings corroborated previous reports on scoliosis and extended understanding of comorbidities, clinical severity, and relative risk reduction for specific mutations. Clinical trial design should account for scoliosis and related factors judiciously.
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Abbreviations
- CSS:
-
Clinical Severity Scale
- MECP2:
-
methyl-CpG-binding protein 2 gene
- MBA:
-
motor-behavioral analysis
- RTT:
-
Rett syndrome
- P:
-
having scoliosis
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Acknowledgements
We acknowledge the gracious participation and provision of information by families of the reported participants, the critical staff support of the International Rett Syndrome Foundation, and the expert guidance provided by Jeffrey Krischer, PhD, and Rachel Richesson, PhD, at the Data Technology Coordinating Center at the University of South Florida. Dr. Mary Lou Oster-Granite, Health Scientist Administrator at NICHD, provided invaluable guidance, support, and encouragement for this Rare Disease initiative.
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Supported by the NIH (NCRR: RR019478/NICHD: HD38985), the International Rett Syndrome Foundation, and the Civitan International Research Center.
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Percy, A., Lee, HS., Neul, J. et al. Profiling Scoliosis in Rett Syndrome. Pediatr Res 67, 435–439 (2010). https://doi.org/10.1203/PDR.0b013e3181d0187f
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DOI: https://doi.org/10.1203/PDR.0b013e3181d0187f
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