How I treat Rett syndrome: impact of trofinetide on symptoms and comorbidities of the disease

Rett syndrome (RTT) is a rare neurodevelopmental disorder primarily associated with mutations in the MECP2 gene that lead to developmental regression and difficulties with language, motor skills, and hand use. Additionally, patients with RTT suffer from seizures, scoliosis, issues with sleep, and behavioral and gastrointestinal issues. Trofinetide is approved for the treatment of RTT in patients aged ≥2 years in the US and Canada. Before this approval, core symptoms of RTT lacked pharmacological intervention, and other symptoms and comorbidities were managed individually causing significant polypharmacy. Additionally, some of these symptoms that lack treatment options rank among the most important symptoms to address according to caregivers of patients with RTT. Here, I present the current pharmacological and nonpharmacological approach I use to manage the symptoms and most prevalent comorbidities of RTT in my practice, highlighting areas where trofinetide is positively impactful and overlaying corresponding caregiver ranking of importance. Future research is needed to determine the effect of trofinetide and concomitant medications on the improvement of RTT symptoms.