A global literature review of comorbidities and concomitant supportive medications among individuals with Rett syndrome
Publication: Journal of Comparative Effectiveness Research
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.
Plain language summary: Understanding the full health burden of Rett syndrome: a review of co-occurring conditions & medications used worldwide
What is this article about?
Rett syndrome (RTT) is a rare genetic disorder that primarily affects girls and causes lifelong problems across many body systems, including the brain, muscles, digestive system and lungs. People with RTT often need multiple medications and care from many different specialists. This review brought together findings from 148 studies conducted in 24 countries to create a comprehensive picture of how common these health problems are and what medications are used to manage them.
What were the results?
Brain-related problems were the most commonly reported, with seizures affecting anywhere from 15 to 91% of people with RTT. Spinal curvature (scoliosis) affected up to 100% of individuals, and digestive problems like constipation (16–83%) and acid reflux (16–100%) were also very common. Sleep difficulties, anxiety, and breathing irregularities were frequently reported across all age groups. To manage these issues, many people required several medications simultaneously seizure medications were used most often, followed by laxatives, acid-reducing drugs and sleep aids.
What do the results mean?
These findings show that RTT causes health problems across multiple body systems throughout a person’s entire life, not just in childhood. Because these health problems are interconnected. For example, worsening spinal curvature is linked to more frequent seizures, therefore care should be coordinated across specialists from an early stage, rather than waiting for symptoms to worsen. Routine monitoring, proactive treatment planning and regular medication review are essential to improving quality of life for people with RTT and reducing the burden on their families.
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Received: 14 May 2026
Accepted: 22 July 2026
Published online: 18 August 2026
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A global literature review of comorbidities and concomitant supportive medications among individuals with Rett syndrome. (2026) Journal of Comparative Effectiveness Research. DOI: 10.57264/cer-2026-0100
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