Decade. Over the past week, winter storm Fern has blanketed large parts of the United States with several feet of snow, leading to a virtual standstill in many regions. When I looked back, I realized that the last major snowstorm that paralyzed public life was a decade ago, a storm called Jonas. Snowed in exactly ten years ago, I reflected on the state of epilepsy genetics. Let’s see what has changed in the field since Jonas in 2016.
Tag Archives: SCN1A
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.
RBFOX3 and the hunt for epilepsy genes in 100,000 genomes
Large scale. Novel epilepsy genes are typically discovered through collaborative studies that combine information across various centers and research groups. However, there are also large-scale sequencing initiatives on a national level that include individuals with epilepsy. In a recent study published in Nature, a wide range of clinical phenotypes were assessed in an initial cohort of 34,000 individuals in the UK 100,000 Genomes Project. Let me dive into the associations related to epilepsy in this publication.
Predicting genetic epilepsies through EMR fingerprints
EMR. Clinical data on rare disease is not necessarily rare; it is our ability to unlock already existing data that is rare. Over the last decade, we have tried to understand the fingerprints that rare genetic epilepsies leave in the electronic medical record (EMR). In our flagship publication last year, we tried to push the boundary. Is EMR data, with all its strength and weaknesses, able to predict genetic diagnosis? Here is our journey through the hidden signals in large EMR datasets.
Takeaways from the 2024 Dravet Syndrome Foundation Biennial Family and Professional Conference
DSF. This June, our team attended the Biennial Family and Professional Conference held by the Dravet Syndrome Foundation (DSF). Over three days in Minneapolis, research findings and therapeutic advances were discussed, and families shared their stories. As a first-time attendee, it was a humbling experience to be invited into this tight-knit, motivated, and inspiring community. Here, I would like to share some of the lessons I learned while in attendance.
SCN1A in FinnGen – epilepsy, dementia, and type 2 diabetes
Isolates. Last week, the FinnGen biobank went live, and Nature dedicated an entire issue to the launch of this initiative. In brief, FinnGen is a large Finnish research project providing genomic and clinical data from a Finnish biobank with the aim to provide new insights into human disease. Finland is an isolated population, which offers unique insights into the role of rare variants in disease. When I checked the FinnGen database for association with SCN1A, I was surprised that three missense variants have been associated with various diseases. Here is what a founder population can tell us about the various roles of SCN1A in human disease. Continue reading
SCN1A gain-of-function, paralogs, and the Philadelphia variant
Between the ion channels. Rather than going “beyond the ion channel,” in this post, we aim to look between them. We want to dive into a study where examining the group of epilepsy-related sodium channels was initially more informative than the single gene itself—even when that gene was SCN1A, the most established epilepsy gene. A recurrent SCN1A variant turned out to be part of an emerging, previously underappreciated gain-of-function spectrum. Here, we discuss the unusual phenotype of SCN1A gain-of-function variants and how we are currently working on integrating information on paralogs into the official ACMG variant curation criteria.
Here are the most frequently read blog posts in epilepsy genetics
2022. In December, our blog passed an important milestone – one million views. Given that Beyond the Ion Channel is a niche blog on epilepsy genetics and pediatric neurogenetics, this is a milestone that we are proud of. In the current post, we would like to examine some of the trends on what people read on our blog. Given that this resource has been around for more than a decade, the topics and genes that people searched for reflect some interesting patterns in the field that may tell us about how information on genetic epilepsy is presented online and what we need to do better. Here are top five most frequently read posts, including some topics that surprised us. Continue reading
AES 2022 – Soundbites from Nashville, Tennessee
Music City. This year’s Annual Meeting of the American Epilepsy Society (AES) took place in Nashville, Tennessee. With a pre-meeting in Memphis and the annual Clinical Skills Workshop as the final event of the annual meeting, our team was able to spend more than a week in the Volunteer State. Yes, there is more than enough music in Nashville and it is virtually impossible to step into a pub, restaurant, or Honky Tonk without live music. Now that my ears have recovered, here is a summary of epilepsy genetics at AES 2022. Continue reading
How SCN1A comes to its own rescue
Modifier genes. When I compiled the most important updates on SCN1A genetics a few weeks ago, I forgot one of the most unusual studies that makes you pause and think. To provide some background: ever since the initial discovery of familial epilepsy syndromes such as Genetic Epilepsy with Febrile Seizures Plus (GEFS+), the intrafamilial range of presentations has been a big mystery. Within single families, we typically observe a very broad spectrum of phenotypes. Furthermore, in some families, the range of phenotypes is extreme – the same SCN1A variant may cause Dravet Syndrome in one individual, while other individuals are unaffected. In a recent study, we stumbled upon an unusual cause for this variability: a second SCN1A variant that neutralizes the pathogenic effect of the familial variant. Here is a summary of this unusual story. Continue reading