Remarkable Seizure Reduction with Trofinetide in An Adult with Rett Syndrome
Abstract number :
2.148
Submission category :
18. Case Studies
Year :
2025
Submission ID :
342
Source :
www.aesnet.org
Presentation date :
12/7/2025 12:00:00 AM
Published date :
Authors :
Presenting Author: Semihan Adegbite, BS – Sidney Kimmel Medical College
Pooneh Memar Ardestani, MD, PhD – Sidney Kimmel Medical College
Maromi Nei, MD – Sidney Kimmel Medical College
Rationale: Rett syndrome (RTT), a neurodevelopmental disorder caused by mutations in the MECP2 gene, often leads to severe cognitive, motor, and behavioral regression. Seizures affect 50-90% of individuals with RTT and are frequently resistant to treatment. Trofinetide, the first approved treatment for RTT, has shown promise in improving core symptoms, though its effect on seizures remains underexplored. We present the case of a late-diagnosed adult with RTT refractory epilepsy with significant clinical improvement and seizure reduction following initiation of trofinetide, highlighting the potential benefits even in delayed-diagnosis scenarios.
Methods: Case presentation: We report the case of a 63-year-old woman with refractory epilepsy. She had normal development until the age of 24 to 36 months, when there was gradual regression, including loss of speech and regression of fine motor skills. She later developed further cognitive decline, spastic diplegia, and epilepsy, with seizures beginning at the age of 13. Seizures were initially nocturnal tonic-clonic seizures, but they later transitioned to daily tonic seizures. Several anti-seizure medications (ASM) were tried but discontinued due to adverse effects and/or lack of efficacy. On lacosamide, the patient continued to have frequent seizures and seizure clusters with up to 3-4 tonic seizures per day, averaging approximately 26 tonic seizures/month. Video-EEG during a typical tonic seizure recorded an electrodecremental response associated with bilateral upper extremity tonic posturing. In addition, severe constipation led to frequent emergency room evaluations. Diagnosis of Rett syndrome (c.380C >T (p.Pro127Leu), mutation in MECP2) was made when the patient was 55 years old through genetic testing. Shortly after trofinetide received Food and Drug Administration (FDA) approval, the patient was started on treatment and, which she has continued for over two years. Since initiating treatment, she has experienced a significant reduction in seizure frequency as well as improvements in behavioral symptoms and constipation. Apart from three clusters of seizures, with one provoked by a urinary tract infection and another occurring after an attempt to reduce the lacosamide dose, the patient has remained seizure-free since starting trofinetide.
Results: N/A
Conclusions: To our knowledge, this patient is the first reported case of an older individual with RTT with significant seizure reduction after starting trofinetide. This suggests that long-term use of trofinetide may result in sustained symptom improvement in older individuals and in people who were diagnosed later in life with RTT. Our patient had seizure recurrence when an attempt was made to reduce the dose of lacosamide. This suggests that trofinetide may have a synergistic effect on seizure control when used with some ASMs. However, further studies specifically designed to evaluate seizure outcomes, as well as specific ASM combinations, are necessary to determine possible benefits of trofinetide in seizure management in Rett syndrome.
Funding: NONE
Case Studies