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.
Monthly Archives: February 2026
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.