Objective:

To characterize the impact of a continuing medical education initiative that incorporated real-world patient scenarios in addressing diagnostic and treatment challenges in Rett syndrome (RTT).

Background:

The approval of trofinetide, the first therapy for RTT, requires greater clinician preparedness in treatment selection, caregiver counseling, and team-based management.

Design/Methods:

A multidisciplinary expert faculty panel developed a multicomponent CME curriculum (a 60-minute foundational module and a three-part, case-based series) centered on practical strategies to facilitate early diagnosis, therapy selection, AE management through neurology–gastroenterology collaboration, and integration of rehabilitation therapy. Real-world cases were gathered via a survey of clinicians who manage patients with RTT. The impact of the program was assessed through pre- and post-tests and intended practice changes. Chi-square tests compared responses (P<0.05; pre/post), effect size was estimated with Cohen’s d.

Results:

As of October 9, 2025, the education had reached 6,207 clinicians (343 on-platform, 5,864 via microlearning). At baseline, the most frequently cited diagnostic challenges were: differential diagnosis of RTT (33%), limited exposure to RTT (26%), and difficulty interpreting early signs in the absence of classic regression patterns (25%). Post education, data demonstrated substantial gains in recognition of early RTT signs (pre 48%, post 78%; P < 0.001), trofinetide efficacy and safety (pre 44%, post 81%; P < 0.001), and competence in AE management (pre 37%, post 79%; P < 0.001). Other areas of noticeable improvement included confidence in multidisciplinary coordination (pre 42%, post 76%; P < 0.001) and in caregiver counseling (pre 29%, post 68%; P < 0.001). The overall educational effect size was large (Cohen’s d = 0.82), with 79% of participants self-reporting intended practice changes, most related to AE mitigation and enhanced team-based collaboration.

Conclusions: