Utilization of Non-pharmacological Interventions in Rett Syndrome: A Systematic Review of the Literature on...

Rett syndrome (RTT) is a rare neurodevelopmental disorder characterized by early childhood loss of mobility, reduced verbal communication, and behavioral impairment. Although non-pharmacological supportive interventions are widely used, there is a need to better understand their role in RTT care globally.

Following PRISMA guidelines and a PICOST framework, a systematic review of white (PubMed, Embase, Cochrane) and gray literature was conducted. Non‑pharmacological interventions examined in the United States (US) and outside the US (OUS) settings included ancillary services (e.g., physical therapy [PT]), assistive devices (e.g., wheelchairs), surgical procedures (e.g., scoliosis correction), and assisted interventions (e.g., enteral feeding).

Across 28 eligible studies, patient ages ranged from 1 to 66 years, and 71.4% focused exclusively on female patients with RTT. Approximately 25.0% of the studies were conducted in the US, while 75.0% were conducted in OUS. Six studies examined ancillary service use, where PT utilization ranged from 24.4% to 100.0% and occupational therapy (OT) ranged from 11.5% to 91.7%. Pediatric patients demonstrated a two- to fourfold higher utilization of PT and OT services compared to adults. Among six studies evaluating assistive devices, wheelchair use was reported in up to 90.0% of patients. Nine studies reported surgical procedures, with 1.2%-50.0% of patients requiring scoliosis surgery. Eighteen studies examined assisted interventions, showing enteral feeding utilization rates from 2.0% to 52.0%.

Despite the universal clinical reliance on non-pharmacological interventions in RTT, the evidence base quantifying their real-world utilization remains sparse. The wide variability in reported rates might be due to differences in data sources, geographic settings, and patient populations which underscores the need for standardized, prospective, longitudinal research. Age-related declines in ancillary service use and geographic gaps highlight systemic disparities that warrant further investigation. These findings provide a foundational evidence base to inform health resource planning and future research priorities in RTT.