CHD2 – here is what you need to know in 2023

Chromodomain. Today is International CHD2 Awareness Day and we are publishing this blog post in time for our CHD2 webinar where we present the result of a four-week sprint to analyze harmonized clinical data. We also updated our gene page on CHD2, which was long overdue. In addition to becoming a more well-known gene, here are three things to know about CHD2 in 2023. Continue reading

Precision medicine in the absence of outcomes

EMR. Genomic data is increasingly available for large patient cohorts. In parallel, healthcare is increasingly digitized and large amounts of data can easily be extracted and analyzed at the click of a button. In principle, this should provide tremendous opportunities to understand how epilepsy care can be personalized based on genetic factors. However, we quickly run into challenges. Obtaining information on seizure frequencies, for example, requires manual chart review. Trying to understand how a person’s genetic makeup affects responses to anti-seizure medications is therefore not possible in large healthcare systems where related questions in other diseases can increasingly be answered. Here is a brief overview of how we can meaningfully engage with clinical data when outcomes are simply not available. Continue reading

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

The history of epilepsy genetics

Timeline. There are a few factors converging at the moment that motivated me to write this blog post. Our blog is officially 14 years old, a fact that has generated surprise, but also nostalgia over the weekend. Second, we were asked to provide an editorial for an interesting review paper by the Lal group, which data-mined PubMed to characterize the history of epilepsy gene discovery. And third, I have heard too often that our 2016 timeline of epilepsy gene discovery that is often used in presentations is antiquated. Let us provide everybody with an update in this blog post. But first, let’s start with a seemingly easy question: what exactly is an epilepsy gene? Continue reading

The millennium variant – SCN1B, gene validity, and GEFS+

800 years. The discovery of SCN1B as a causative gene for Genetic Epilepsy with Febrile Seizures Plus (GEFS+) was one of the most pivotal moments in epilepsy genetics. This discovery not only shaped our understanding of the channelopathy concept, but also highlighted the importance of careful phenotyping. Therefore, it may be surprising that SCN1B took almost a quarter of a century to accrue sufficient evidence to be considered as a definite epilepsy gene. However, this is not the only aspect where SCN1B operates on its own time scale. In a recent publication, one of the most common disease variants in SCN1B could be traced back more than 800 years to a single founder event. Here is a 2023 update on the journey of one of the most well-known but also most mysterious epilepsy genes whose origins are lost in the depth of time. Continue reading

This was epilepsy genetics in 2022

Looking back. This is our final blog post for 2022 and a good opportunity to look back at what happened in the last 12 months in epilepsy genetics. In brief, it was a busy time and if I were to look back at 2022 in a few years, I would probably characterize this year as a transitional year. Antisense oligonucleotides, gene therapies, and other novel treatments are on the horizon, but the field is not quite there yet. For this blog post, I would like to put the focus on five discoveries in 2022 that did not receive as much attention on our blog as they probably should have. Continue reading

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

Walking in Memphis – TARGETing Epilepsy at St. Jude

Memphis, TN. Prior to this year’s AES meeting, the epilepsy genetics community descended upon St. Jude Children’s Research Hospital in Memphis. I had previously largely associated St. Jude with pediatric cancer treatment, but within the last few years, a large-scale pediatric neuroscience program was launched, putting Memphis on the epilepsy genetics map. And with Heather Mefford’s new lab, the program at St. Jude includes one of the major epilepsy genetics groups. While blogging about scientific meetings is always tricky, one particular quote from the first day struck me as particularly relevant for the current state of therapeutic development: “quick, but not too quick”. Here is where the field of epilepsy genetics and precision medicine finds itself at the end of 2022. Continue reading

CACNA1A – five things to know in 2022

Epilepsy genes. It has admittedly been quiet around the gene pages on our blog and many pages require an update. When we initially launched the Epilepsiome pages, we wanted to create a small resource for gene-based information according to the “what you need to know” principle, a condensed digest regarding epilepsy genes written by clinicians and researchers with deep expertise in the field. We chose CACNA1A as the first gene to get an update. The reason for this is the following: Laina has taken on the role of modernizing this blog and CACNA1A is the main condition that she is working on. Here are five things to know in 2022 about CACNA1A. Continue reading