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Observational Study
. 2025 Aug;55(8):2873-2883.
doi: 10.1007/s10803-024-06399-y. Epub 2024 May 25.

Orthopedic Conditions and Interplay with Functional Abilities and MECP2 Variant Subtype in Rett Syndrome Patients

María Galán-Olleros #  1 , Elena González-Alguacil #  2 , Víctor Soto-Insuga  2 , María Teresa Vara-Arias  3 , Nelmar Valentina Ortiz-Cabrera  4 , J Ignacio Serrano  5 , Rosa M Egea-Gámez  6 , Juan José García-Peñas  2 , Ignacio Martínez-Caballero  6 ; RTT-HNJ, Rett Syndrome Multidisciplinary Group of Hospital Infantil Universitario Niño Jesús
Collaborators, Affiliations
Observational Study

Orthopedic Conditions and Interplay with Functional Abilities and MECP2 Variant Subtype in Rett Syndrome Patients

María Galán-Olleros et al. J Autism Dev Disord. 2025 Aug.

Abstract

Purpose: Rett syndrome (RTT) is a rare multi-systemic disorder primarily linked to mutations in MECP2 gene. This study aims to describe the prevalence of orthopedic conditions in RTT patients, and examine their intricate interplay with functional capabilities, and MECP2 variant subtypes.

Methods: Conducted as a cross-sectional retrospective observational study, the research encompassed 55 patients meeting clinical RTT criteria and holding MECP2 mutations. A review of clinical records was performed to gather demographic data, mutation subtypes, orthopedic conditions, management strategies, and assessments of function.

Results: Mean age of the participants was 10.22 ± 4.64 years (range, 2.9-19.41). Prevalence rates of orthopedic conditions were as follows: kyphoscoliosis 63.6%, hip displacement 14.6%, knee problems 40%, and foot deformities 75.5%. Significant relationship emerged between spinal (p < 0.01) and knee deformities (p < 0.01) with reduced motor function across various domains. Hip displacement significantly affected sitting ability (p = 0.002), and foot deformities impacted standing and walking capabilities (p = 0.049). Mutation clusters analysis revealed significant correlations with spinal (p = 0.022) and knee deformities (p = 0.002). Linear models highlighted the critical importance of mutation clusters, spine deformities, age, and hip management concerning functional variables.

Conclusions: In this study, foot deformities were the most frequent orthopedic manifestation, followed by spinal, knee, and hip deformities; and unveiled their relationships with functional status and groups of mutations in RTT patients.

Level of evidence: Level IV, Case series.

Keywords: MECP2 mutation; Functional assessment; Orthopedics; Rett syndrome; Scoliosis.

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Conflict of interest statement

Declarations. Conflict of Interest: The authors report there are no competing interests to declare. Ethical Approval: The study was approved by the Institutional Review Board (n°. R-0106/23). This study was performed in accordance with the ethical standards in the 1964 Declaration of Helsinki. Protocol: This manuscript adhered to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines for reporting observational studies. The study design and reporting have been structured in accordance with the STROBE checklist to ensure transparency and comprehensive reporting of our research findings. Quality Assessment: All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.

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