Families. We tend to think that we understand familial epilepsy. The mental image is almost fixed: large pedigrees, clean inheritance, recognizable syndromes, and genes that segregate exactly as expected. But in a recent study from our epilepsy genetics program, we looked at something different. Not discovery cohorts and carefully selected multiplex families, but real-world genetic testing in 484 consecutive families. All families were evaluated in routine clinical care through ENGIN, our Epilepsy Neurogenetics Initiative, which has now evaluated more than 7,000 individuals with epilepsy and related disorders. The result was a picture of familial epilepsy that is both reassuring and unexpectedly complicated. Here is what we found. Continue reading
The Landscape of Communication in Genetic Neurodevelopmental Disorders
Signals. Communication is one of the clinical domains that we talk about often in genetic neurodevelopmental disorders, but surprisingly rarely study across disorders in a systematic way. In a recent preprint, the authors used large-scale research datasets to map communicative abilities across many genetic conditions linked to neurodevelopmental disorders and autism, asking a simple but powerful question: can we see disorder-specific patterns when we look at communication at scale? Here is what the authors found.
Phenotypes Are Like Water – Rare Disease Day 2026
Water. Three years ago, on Rare Disease Day 2023, I published a blog post comparing phenotypes to water, existing in three phases: solid, liquid, and vapor. At the time, I was trying to make a simple point. Rare diseases are not defined by their first description, nor only by a checklist of features. They are moving targets. Here is what has changed since then.
An Atlas into Pediatric Neuroimmunity
CSF. Even though our blog focuses on neurogenetics, there is a much wider range of rare diseases in child neurology, including many conditions that may not even have names yet. One emerging category is pediatric neuroimmune disorders. In a recent publication generating CSF immune profiles in these conditions, we contributed by providing the framework for pediatric sample acquisition. Here is what we learned and why ongoing biobanking is critically important in child neurology.
Decoding CACNA1A: How Function Shapes Phenotypes
Cav2.1. Among the various neurogenetic disorders that we follow in our clinic, CACNA1A-related disorders are somewhat unique. Even though these conditions have been known for several decades, our understanding has remained fragmented, and the functional effect of most missense variants is still not well understood. In a recent study, we contributed to a comprehensive functional assessment of 42 missense variants in CACNA1A, approaching the problem in a structured, top-down manner. Here are the main findings from our study.
Glymphatic System, Mirror Neurons, and Other Stories We Tell Ourselves
Glymphatic. I stumbled over the term glymphatic system last week and briefly had to pause. The concept is now widely used and feels intuitive, but it did not exist when I was in medical school. The term was only introduced in 2012 to describe a glia-dependent, perivascular clearance pathway in the brain. And yet, everything it refers to, including perivascular spaces, astrocyte endfeet, cerebrospinal fluid flow, interstitial clearance, was already in the textbooks. All the parts were familiar to me, but the label was new. That moment of confusion stayed with me: neuroscience moves forward not just through data, but also through names.
Minimal Fusion at WHX 2026
Improbable. A global metropolis rising from open desert simply should not exist. It should not work climatically, economically, or historically. And yet Dubai did it. At this year’s World Health Expo WHX in Dubai, one of the largest global healthcare gatherings with more than 60,000 participants, visitors entering the South Hall were greeted by a large-scale animation of synaptic vesicle fusion, the SNARE complex zippering into place guided by MUNC-18 (STXBP1). We developed this display to visualize mechanisms in genetic neurodevelopmental disorders. Watching this animation, I thought about improbability and about what makes complex systems succeed.
The Long Arc of TBC1D24
Arc. Among the various synaptic disorders, TBC1D24 remains one of the more mysterious conditions. Although this genetic epilepsy was first described in 2010, the trajectory of symptoms over time has been poorly understood. In a recent publication, we reconstructed longitudinal seizure histories and developmental trajectories from electronic medical record data. What emerged was a disorder that dramatically changes shape over time. Here is what we found.
USP25 and the gravity well of evidence
Evidence. I was a contributor to a recent commentary questioning whether the USP25 gene should currently be considered a validated gene for genetic generalized epilepsy. The motivation behind this commentary was not to challenge the initial data, but to ask what happens when a claim for gene validity encounters the full weight of accumulating evidence. Does USP25 remain robust as our expectations for validation rise? Or has it reached the point where additional evidence no longer supports the initial discovery?
Cure vs. treat: the Babel problem in rare disease language
Language. There are a few words in medicine that seem simple until you say them out loud in front of the wrong audience. In rare disease clinics, two of them are cure and treat. We use them constantly, sometimes interchangeably, and rarely stop to ask what they do to hope, to expectations, and to the quiet contract between clinicians and families. In rare disease, language is not a neutral medium. It is an intervention.