Rett syndrome imposes a substantial, lifelong multisystem burden requiring continuous surveillance and anticipatory, multidisciplinary care rather than symptom-driven management.
A global literature review of 148 studies across 24 countries found that Rett syndrome is associated with high prevalence of neurological, musculoskeletal, and gastrointestinal comorbidities, including epilepsy (15-91%), scoliosis (8.9-100%), constipation (16.4-82.8%), and gastroesophageal reflux (15.8-100%). Medication use is common, with antiepileptic drugs being the most frequent (monotherapy 14.3-33.0%), followed by proton-pump inhibitors (37-61%), melatonin (7.7-30%), and anti-anxiety agents (10-21.4%). The findings support proactive, coordinated care and routine medication review.
Evidence Score
Study Evidence
Study 1. A global literature review of comorbidities and concomitant supportive medications among individuals with Rett syndrome.
observationalRashid N, Rajagopalan K, Syed SS, Okeke CM, Nechi RN, Yunusa I · Journal of comparative effectiveness research (2026)
Result:
Mechanism Graph
Limitations
- ⚠The review is descriptive and does not provide meta-analytic effect sizes or statistical synthesis.
- ⚠Prevalence ranges are wide, reflecting heterogeneity across studies and potential differences in diagnostic criteria or populations.
- ⚠The review may be subject to publication bias, as it excluded non-English articles and case reports.
Frequently Asked Questions
What are the most common comorbidities in Rett syndrome?▼
The most common comorbidities are neurological (e.g., epilepsy, with prevalence up to 91%), musculoskeletal (e.g., scoliosis, up to 100%), and gastrointestinal (e.g., constipation up to 82.8% and gastroesophageal reflux up to 100%).
Which medications are most frequently used in Rett syndrome?▼
Antiepileptic drugs are the most common, with monotherapy reported in 14.3-33% of patients. Other commonly used medications include proton-pump inhibitors (37-61%), melatonin (7.7-30%), and anti-anxiety agents (10-21.4%).
Does Rett syndrome affect only children?▼
No, Rett syndrome is a lifelong condition. The review included participants aged 7 months to 37 years, and the findings indicate that the multisystem burden persists throughout life, requiring continuous surveillance.
Why is multidisciplinary care recommended for Rett syndrome?▼
Because Rett syndrome affects multiple body systems simultaneously, and comorbidities are interconnected (e.g., worsening scoliosis is linked to more frequent seizures), coordinated care across specialists is essential for proactive management rather than waiting for symptoms to worsen.
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References
- 1.Rashid N, Rajagopalan K, Syed SS, Okeke CM, Nechi RN, Yunusa I. "A global literature review of comorbidities and concomitant supportive medications among individuals with Rett syndrome.." Journal of comparative effectiveness research, 2026. PMID: 42610386 DOI: 10.57264/cer-2026-0100