Fusion. If you have ever tried to merge soap bubbles, you know the paradox. Soap bubbles look soft and fragile, but the moment you bring them close, they push each other away. Membranes behave similarly. A synaptic vesicle and the presynaptic membrane do not naturally want to merge. They repel each other. Therefore, synaptic vesicle release requires a mechanism that overcomes this resistance, holds two membranes in close contact, and then triggers fusion on demand within milliseconds. In a recent paper, that mechanism is brought into focus through UNC13A, a gene encoding one of the central priming factors that makes synaptic fusion possible. Here is what the study shows.
The MACF1 puzzle: when a cytoskeletal giant causes multiple brain disorders
Connections. Spectraplakins sit at the interface of architecture and motion inside a cell. They do not merely hold structures together but coordinate how the cytoskeleton rearranges itself when neurons migrate, polarize, and extend processes. One of the central spectraplakins is encoded by MACF1, a microtubule–actin crosslinking factor that couples microtubules to actin filaments and helps steer growing microtubules. This job requires multiple binding domains, flexibility, and scale. Spectraplakins are therefore large proteins encoded by enormous genes. A recent study examined how variants in MACF1 translate into human brain disease, and why seemingly similar variants may lead to surprisingly different neurodevelopmental outcomes. Here is why interpreting MACF1 variants is so complex.
Signals in the noise – qEEG patterns in genetic epilepsies
qEEG. The electroencephalogram is one of the oldest tools in neurology. We use it every day to diagnose and monitor brain function, yet, even in the era of genomic medicine, most of our EEG interpretation still relies on visual inspection, a human reading of squiggled traces. In a recent publication in Neurology, we asked whether the information embedded in these signals could be measured more objectively in children with STXBP1, SCN1A, and SYNGAP1-related disorders. Here is the story on how we identified hidden signals in the EEG tracings of individuals with genetic epilepsies.
The quiet revolution – revising ACMG criteria for epilepsy genes
VUS. The story begins with a patient in clinic. A young child with severe epilepsy, carrying a variant in SCN1A, the classic gene for Dravet Syndrome. But the variant is labeled a variant of uncertain significance (VUS). Dravet Syndrome is a clinical diagnosis, and the treatments we have today do not hinge on whether the variant is clearly pathogenic or not. But then we wonder whether a novel precision therapy could be an option, and we look up inclusion criteria and hesitate. Trial frameworks often require a variant to be pathogenic or likely pathogenic, and future precision medicine approaches in routine clinical care may require the same. For this patient, a VUS is a door that does not open. Here lies the quiet revolution in epilepsy genetics that is unfolding in the background: the refinement of variant interpretation itself.
The gentle singularity that cannot draw a synapse
Singularity. A few months ago, Sam Altman, the CEO of OpenAI, published a short essay about the future of artificial intelligence. His central message was a gentle role for AI—a vision in which technology supports us quietly in the background rather than staging some dramatic takeover of human life. What caught my attention, however, was not the word “gentle” but the word “singularity.” For science fiction readers, this term carries weight. It evokes images of runaway technology, accelerated futures, and the moment when machines surpass human intelligence. Yet in the world I inhabit, working with rare diseases and clinical genetics, the reality is far more modest. AI is entering our lives in practical, incremental ways. And despite its advances, one telling detail remains: it cannot draw a synapse. This small but persistent limitation says something important about where we are—and where we are not.
Influenza and acute necrotizing encephalopathy – the genetic dimension
ANE. A rare complication with hidden genetic clues. Imagine a healthy child who goes to bed with a fever and wakes up unable to recognize their parents, slipping rapidly into coma. This is the terrifying course of acute necrotizing encephalopathy (ANE), one of the most severe neurological complications of influenza. In a recent study, children with influenza who developed ANE showed an unexpected pattern: nearly half of those tested carried genetic variants that might predispose them to this devastating complication.
Different genes, convergent processes – rare disease lessons from neurogenesis
A paradox in the hippocampus. Immature dentate granule cells are often described as the “plasticity reserve” of the hippocampus. They provide a pool of neurons that integrate into existing circuits, supporting learning, memory, and repair. In neurological disease, these cells have been suggested to buffer against injury or degeneration. In a recent publication, researchers showed that the hippocampus continues to generate new neurons throughout life, but that the molecular instructions for doing so vary dramatically across species. The surprising finding is this: the processes of neurogenesis are conserved, while the genes underlying these processes are often completely different. This is an important reminder that biology often converges at the level of function, even when the building blocks are not the same.
The placental mirror – methylation and neurodevelopment in congenital heart disease
Neurodevelopment. Congenital heart disease (CHD) refers to a broad group of structural abnormalities of the heart that are present at birth and affect approximately 1% of all live births. Over the past two decades, advances in neonatal surgery and perioperative care have dramatically increased survival rates. Yet this success has revealed an important challenge, and focus has gradually shifted from the heart alone to the brain. A growing body of evidence has shown that children with CHD are at increased risk for neurodevelopmental disorders, including delayed language acquisition, executive dysfunction, and visuospatial processing difficulties. In a recent publication, we took advantage of a unique biorepository to explore how early differences can be identified on the molecular level that may inform later neurodevelopmental features. Here is what we found.
Three things the beach told me about science in 2025
Rehoboth. It has been a while since I posted my annual post-beach-vacation thoughts about how my experiences at the shore made me think about science. I initially started these posts after a vacation in Marielyst, Denmark when I realized that my sandcastle building skills were not appreciated as much as I thought. This reminded me that similar things happen with our scientific achievements. Here is what the beach told me about science in 2025, twelve years after I started to compare academic endeavors with alluvial relaxation. Continue reading
Chasing the Demosthenes gene – the complex genetics of stuttering
Fluency. When we think of stuttering, we might first think of speech therapy, of pauses and repetitions, and of the courage it takes to speak when words get stuck. But what if we could step back and see its genetic architecture laid out across the globe? A recent study looked at the genetics of stuttering at an unprecedented scale: over 1.1 million individuals, including almost 100,000 people who self-reported a history of stuttering. Stuttering shows a significant overlap with other neurodevelopmental disorders and enrichment of genes expressed in the brain. Here is a brief summary of one of the most important studies in stuttering research in the last few decades.