Westminster. The Westin in Westminster, Colorado has an inbuilt alarm clock. As the hotel is a relatively isolated tall building, you get the most intense sunrise over the big Colorado sky that gently wakes you up as it intensifies – a consolation prize if your hotel room doesn’t have the majestic mountain view, as was my case this year. The Westin the venue for this year’s STXBP1 Summit+ Family Meeting. Here are three takeaways from the summit, from my perspective as a clinician researcher.
Figure 1. Impressions from the 2025 STXBP1 Summit+, including Sarah’s award as the 2025 Clinical Champion, our “Bee Brave” painted stone at our conference table, the interactive word cloud at the start of the meeting, the epic Colorado sunrise, and a view of the Westin in Westminster, Colorado that hosted the STXBP1 family meeting for the second time in 2025. More impressions of the 2025 STXBP1 Summit+ can be found at https://www.stxbp1disorders.org/2025-summit.
Denver. Over the last few years, we have established a rhythm of meetings for STXBP1-related disorders. Every year, there is both a family summit and a scientific meeting. This year, the scientific meeting will take place in Heidelberg, Germany from October 8-11 and the STXBP1 Family Summit returned to Westminster, Colorado where we held the first summit two years ago. Given the rapid development in the STXBP1 field, it was a very exciting time to have a meeting specifically geared towards our STXBP1 families. Knowing that I won’t do the meeting justice by focusing on a subset of takeaways, here are three things I learned during this year’s Summit.
1 – A disease understood and explained. I did something unusual this year when I prepared my presentation on the clinical update on STXBP1. Knowing that many other speakers covered our STXBP1 natural history study (STARR), including specific clinical features such as autism characteristics, qEEG biomarkers, and considerations for upcoming gene therapy trials, I cut down on the content of my presentation. My idea was to spend less time adding content and more time explaining. Our current knowledge on STXBP1 is solid enough that we can apply it in a clinical setting, for example, we can determine the likelihood of seizures at certain ages, transitions between seizure types, and the average age of independent walking. I tried to change the focus from “understanding” to “explaining” and realized for the first time that STXBP1 is truly a condition that we can confidently explain in a way that gives families certainty amongst all the uncertainty that genetic diagnoses typically carry.
2 – Awards and 25 years of STXBP1 research. Several awards were handed out during this year’s STXBP1 Summit+ Family Meeting. And I would like to point out that Paula Rinaudo, who won the Everyday Hero Award, and the Baum family, who won the Transformative Changemakers Award, found themselves in historic company. It has been 25 years since Matthijs Verhage from VU Amsterdam published the first major paper on STXBP1 (I was in medical school back then). Matthijs was awarded the Innovative Research Award for spending the last quarter century thinking about and working on STXBP1. The Clinical Champion Award went to Sarah Ruggiero from our CHOP/Penn ENDD Center, which complements Matthijs’ award in a unique way. Sarah, in addition to having built the clinical ENDD program that gave rise to our STARR study, has talked to roughly 25% of the US STXBP1 population and has seen more STXBP1 families than any other person in the world. From gene discovery to calling any family with STXBP1 back within less than 25 hours. Congratulations Paula, Baum family, Matthijs, and Sarah!
3 – From fastest growing knowledge to solid foundation. There were several references to STXBP1 as the “rare disease with the fastest growing knowledge”, a title that our community acquired three years ago when we first presented our combined international efforts to decipher the unusual phenotypic landscape of a rare neurodevelopmental disorder with epilepsy that had previously puzzled clinicians due to its unpredictability. The “fastest growing knowledge” label reflects the fact that our clinical understanding on STXBP1-related disorders emerged virtually out of nowhere in the last five years and now includes FDA-compliant natural history data on more than 100 individuals, trial-ready qEEG biomarkers that align with developmental milestones, tremor assessments using wearables, and the first gene therapy clinical trials enrolling patients. Accordingly, we are at an inflection point in our understanding of STXBP1-related disorders. It is no longer a “start-up disease” where we need to fill in the blanks in an unknown landscape. Our knowledge forms a solid foundation to move ahead with clinical trials and ask focused research questions. However, “rare disease with the fastest growing knowledge leading to a solid knowledge base for clinical trials” is a bit of a mouthful and probably less memorable. Let’s see what title will be given to our community next.
What you need know. I picked three key personal takeaways from this year’s STXBP1 Summit+ Family Meeting. In contrast to the annual scientific meeting, this Family Summit always has its own kind of magic and allows us to connect with the STXBP1 community outside of clinic visits and natural history studies. From the viewpoint of a clinician-scientist, the STXBP1 Community is thriving, which is an important motivator to keep pushing ahead, for both junior and senior scientists. Thank you to the organizers and I’m already looking forward to the next Summit!
