Authors :
Presenting Author: Kirsten Eschermann, MD – Paracelsus Medical University Salzburg
Verena Schmeder, BS – SYNGAP Elternhilfe e.V.
Marcos Mengual Hinojosa, MS – SYNGAP Elternhilfe e.V.
Gerhard Kluger, Prof – Schön Klinik Vogtareuth, Germany, PMU Salzburg, Austria
Milka Pringsheim, MD – Paracelsus Medical University, Salzburg, Austria
Till Hartlieb, Paracelsus Medical University, Salzburg, Austria – Research Institute for Rehabilitation, Transition and Palliation
Celina von Stülpnagel, MD – Paracelsus Medical University, Salzburg, Austria
Daniel Weghuber, MD – Paracelsus Medical University, Salzburg, Austria
Martin Zenker, MD – Otto- von-Guericke University, Magdeburg, Germany
Lorenz Kiwull, MD – Paracelsus Medical University
Rationale:
SYNGAP1-related encephalopathy is a rare developmental and epileptic encephalopathy with urgent need for disease-modifying therapies. To evaluate clinical trial readiness, we conducted a rapid global survey of patients and caregivers using the PATRE registry platform (PATient-Based phenotyping and evaluation of therapy for Rare Epilepsies, www.patre.info).
PATRE is part of EURAS, the EUropean network for neurodevelopmental RASopathies, which aims to accelerate the development of treatments for Cardio-facio-cutaneous syndrome, Costello syndrome, Noonan syndrome and SYNGAP1-related encephalopathy. The Horizon Europe project was initiated by the German SYNGAP1 patient organisation and its medical advisory board.
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Methods:
Within a two-week period in June 2025, a structured digital survey was disseminated via an app to families enrolled in the PATRE SYNGAP1 registry. The survey assessed willingness to participate in clinical trials, attitudes toward different treatment modalities and trial procedures, and priorities for symptom domains to be targeted.
Results:
A total of 197 patients/families participated (N=197), which is about two thirds of the enrolled patients.
Overall, 75% indicated interest in participating in future clinical trials, while only 6% were opposed and 19% were unsure. For early-phase drug trials, 43% reported willingness to participate, with 41% undecided. With respect to intrathecal administration every 2–3 months, 20% agreed outright and 38% would consider it if efficacy was high. Regarding travel, 36% were willing to travel >500 km within Europe, 26% within their country ( >200 km), and only 5% were not willing to travel. The most important therapeutic targets identified by families were epilepsy, behavior/aggression, and cognitive function, followed by communication, motor skills, sleep, and gastrointestinal symptoms.
Notably, a separate analysis by patient age showed that for children under 12 years, both overall willingness to participate (80%) and readiness to travel were even higher. Furthermore, the survey data can, if required, be matched with existing registry information such as clinical severity, validated scores, and the specific SYNGAP1 mutation type for trial planning.
Conclusions:
This large, rapid, app-based survey demonstrates that the SYNGAP1 community is highly motivated and ready to engage in clinical trials. The data highlight both enthusiasm for participation and realistic considerations regarding trial design. Importantly, the study underscores the feasibility and performance of the PATRE digital registry as a powerful tool for community engagement, rapid data collection, and trial support in rare epilepsies.
Funding: EURAS is funded by HORIZON EUROPE / the European Commission Grant no. 101080580