Prevalence of orthopaedic conditions in Rett syndrome: a systematic review and meta-analysis

Rett syndrome (RTT), a developmental disorder primarily affecting girls and linked to methyl-CpG binding protein-2 (MECP2) gene mutations, presents musculoskeletal abnormalities with varying prevalence across studies and age groups. Our aim was to delineate the prevalence of orthopaedic conditions in individuals with RTT.

Three databases were searched and independently screened by two reviewers to retrieve observational studies published after 2000 that recruited 10 or more patients diagnosed with RTT and reported the prevalence of any orthopaedic conditions (scoliosis, hip displacement, knee problems or foot deformities). A random-effects meta-analysis was performed to determine the pooled prevalence based on study weight.

Of 867 screened studies, 21 studies involving 9997 girls with RTT (mean age 14.1 years; range, 3-38.5) met the inclusion criteria. The pooled prevalence of scoliosis was 64.5% [95% confidence interval (CI) 55.4-73.6%; I² = 99%; P < 0.01], of hip displacement was 29.6% (95% CI 8.9-50.2%; I² = 97%; P < 0.01) and of foot deformities was 53% (95% CI 17.5-89.2%; I² = 98%; P < 0.01). Knee problems were reported in only one study. Scoliosis prevalence increased in studies with a high percentage of genetic testing and MECP2 positivity [69.1% (95% CI 58.9-79.2%; I² = 99%; P < 0.01)], those with a mean age over 13 years [73% (95% CI 59.1-87%; I² = 100%; P < 0.01)], and studies combining both variables [80.13% (95% CI 70.8-89.4%; I² = 81%; P < 0.01)].

This meta-analysis found that approximately two in three girls with RTT develop scoliosis, one in two exhibit foot deformities and one in three experience hip displacement. These findings enhance our understanding of the prevalence of orthopaedic conditions in RTT, which can guide the establishment of surveillance protocols, clinical guidelines and management strategies tailored to the needs of RTT patients.