DCM. This is my second blog post on SYNGAP1-related disorders within a month, which highlights how fast the area of clinical trial readiness is moving for one of the most common synapse disorders. Over the last few years, we have become more and more attuned to the fact that readying genetic epilepsies for clinical trials requires a systematic approach. The first step in this process is a disease concept model (DCM). In a recent publication in Pediatric Neurology, the authors comprehensively mapped the lived experience of SYNGAP1-related disorders. Here is what the authors found.
Monthly Archives: June 2025
The 70-mile synapse – riding for Lulu’s Crew
MDBR 2025. Imagine a sugar cube-sized piece of our brain. Within this small segment of neuronal tissue, the total length of nerve fibers amounts to approximately 70 miles. This is exactly the distance I rode for the 2025 Million Dollar Bike Ride last Saturday as a member of Lulu’s Crew. Here is my blog post on a different kind of fundraising for rare disease research, the type of advocacy that has raised more than a million dollars for STXBP1 in the last seven years while making your legs feel like Jello.
CACNA1A-related hemiplegic migraine—the big unknown
FHM. There are few neurological phenomena that are as perplexing as CACNA1A-related hemiplegic migraines. Neither migraines, seizures, nor strokes, CACNA1A-related hemiplegic migraines are poorly characterized neurological events that often defy explanation. In a recent publication, we characterized how hemiplegic migraines in children with CACNA1A-related disorders present across time. Here is what we found.
Out of sync – HCN2, epilepsy, and the h-current current
Funny current. Neuronal firing patterns rely on the coordinated interplay of ion channels, mediating different aspects of how neurons fire and repolarize. In the early 70s, a strange phenomenon was observed: an ion current that became active when it shouldn’t. Subsequently named the h-current or funny current, it activates when neurons are at their resting potential, pulling them away from their resting membrane potential and helping with pace-making. HCN channels are the molecular equivalents of the h-current. In a recent publication, Houdayer and collaborators explore the phenotypic consequences of mutations in HCN2, one of the key components mediating the neuronal h-current. Here is a brief summary of the unusual clinical spectrum associated with variants in HCN2.
A bittersweet goodbye – my decade on the ILAE Genetics Commission
Stepping down. You may have noticed that the ILAE logo on the blog has disappeared. After having served on the ILAE Genetics Commission for roughly a decade, I decided to step down. It is somewhat of a bittersweet feeling. Being part of the international epilepsy genetics community has always been very important to me. However, over the last two years, I realized that I could no longer devote the effort to the ILAE that I wanted to. We were incredibly busy in two new areas: clinical trial readiness studies for STXBP1 and SYNGAP1 and our data-driven analyses of natural histories in genetic epilepsies. Here is a brief personal overview of the three things that made the ILAE Genetics Commission special during this time. Continue reading
Understanding the SCN8A fingerprint through real-world data
Nav1.6. It has been several years since I last wrote a blog post about SCN8A. A wide range of clinical presentations have been described since, and significant progress has been made towards understanding the disease mechanism. However, SCN8A-related disorders have not become less puzzling. In a recent publication, we tried to understand whether SCN8A-related disorders have a unique clinical profile by harmonizing the electronic medical record data of 82 individuals across more than 600 patient years. Here is what we found.