A global literature review of comorbidities and concomitant supportive medications among individuals with Rett syndrome.

Abstract

Aim: To synthesize evidence on the multisystem clinical burden of Rett syndrome, integrating comorbidity prevalence and concomitant medication use to inform proactive care. Materials & methods: A structured search of PubMed, Embase and Cochrane (January 2000 to July 2024), plus gray literature, identified clinical trials, observational studies, registries, and case series (n >10). Non-English articles, case reports, reviews and commentaries were excluded. Two investigators independently screened studies, extracted data and synthesized the evidence using a descriptive approach with evidence mapping. Results: Of 6253 records screened, 148 studies met inclusion criteria, spanning 24 countries and participants aged 7 months to 37 years. Neurological, musculoskeletal and developmental manifestations predominated (reported in 62.0%, 44.0% and 41.0% of studies, respectively). Epilepsy prevalence ranged from 15.0% to 91.0%, scoliosis 8.9-100% and gastrointestinal dysfunction was common, including constipation (16.4-82.8%) and gastroesophageal reflux (15.8-100.0%). Hand stereotypies were reported in 11.4% of studies, with prevalence of 70.0-100.0%. Among studies reporting developmental burden, inability to walk ranged from 19.0% to 100.0%. Additional comorbidities included sleep, oral, and endocrine disorders, among others. Antiepileptic medications contributed most to treatment burden (14.3-33.0% for monotherapy). Other commonly used medications targeted sleep (melatonin, 7.7-30.0%), gastrointestinal symptoms (proton-pump inhibitors, 37.0-61.0%) and behavioral symptoms (anti-anxiety agents, 10.0-21.4%). Conclusion: Rett syndrome imposes a substantial, lifelong multisystem burden requiring continuous surveillance. Findings highlight the importance of anticipatory, multidisciplinary care rather than symptom-driven management. Patterns of medication use, particularly for epilepsy, reflect reliance on symptom-directed therapies and highlight the need for routine medication review, careful prescribing and longitudinal monitoring to optimize outcomes.