How to find recessive disease genes for epileptic encephalopathies

The E2 story continues. There has been major progress in identifying the role of de novo mutations in infantile spasms and other epileptic encephalopathies. Over the last two years, more than 20 new genes for epileptic encephalopathies were discovered and we have good evidence suggesting that de novo mutations play a major role in these disorders. Moreover, we have gotten a good sense on how complicated it can be to call a de novo mutation pathogenic given the flood of rare genetic variants in the human genome. However, de novo mutations are not what we think about clinically when assessing a patient with new-onset epileptic encephalopathy. In a clinical setting, we are often concerned about underlying metabolic disorders, many of which are recessive. Accordingly, we felt that the next task of the E2 consortium was to assess the role of inherited variants in epileptic encephalopathies. Just to tell you in advance, it is not as easy as it sounds.

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Have we given up on the genetics of febrile seizures?

Fever, genes, and seizures. Undoubtedly, febrile seizures are the most common epilepsy syndrome in humans. Up to 5% of children have febrile seizures. In most children, these febrile seizures are self-limiting, and there is no recurrence. Usually, no long-term treatment is required. We know from family studies and twin studies that febrile seizures have a significant genetic component. Now here are two surprising facts: first, the genetic contribution to febrile seizures is entirely unknown. Secondly, to my knowledge, the genetic contribution to the most common epilepsy syndrome in man has not been addressed in any of the current large-scale studies. Let’s review why this is the case and why we should change this. Continue reading

Should we stop talking about heritability in 2014?

Genetic epidemiology. Long before the first epilepsy gene was discovered, clinicians and researchers were wondering about a genetic contribution to epilepsy. Some epilepsy syndrome were found to run in families in an autosomal dominant or recessive pattern. In other epilepsies, there was an obvious excess of affected family members in the immediate or extended family. And this is how we got stuck with the concept of heritability. Let’s review the perils and pitfalls of heritability and ask the question whether we should retire this concept in the current era of genomic medicine. Continue reading

When will we have the $1000 epilepsy genome?

Falling prices. The initial Human Genome Project took 10 years and cost more than $3 billion US Dollars. The $1000 genome catch phrase was first used in 2001 and indicated that prices would need to fall significantly to allow for genome sequencing to be used for routine diagnostics. Currently, in 2014, the $1000 genome seems on the horizon. However, will we ever have a $1000 epilepsy genome? Continue reading

The top three publications in epilepsy genetics 25 years ago

Looking back. In this week’s ILAE Genetics Commission post, we would like to look 25 years back and examine the most important publication in the field in 1989, the year the Berlin wall fell. What concepts did we have back then and how did our understanding of epilepsy and genes change? Here are the top three publications of 1989. Continue reading

Precision medicine in genetic epilepsies – three criteria to consider

Three criteria. You hear the phrase precision medicine quite frequently these days and might wonder what this is all about. In a nutshell, in the context of genetic epilepsies, the basic idea behind precision medicine is to use genetic patient information for treatment decisions. The broader vision behind this aims at improving the lives of individuals with epilepsy by making smarter and faster treatment decisions, which lead to better treatment response and fewer side effects. But how should we assess information on reports of precision medicine in the literature? Here are the three important criteria to assess. Continue reading

We want you to be an Epilepsiome builder

YESTI. On behalf of the ILAE Genetics Commission, we are looking for young clinician scientists who would like to help us build the Epilepsiome – a comprehensive, up-to-date database on epilepsy and genes. We are looking for YESTI’s – “young experts with sufficient time and interest”. Read more about what we would expect from you. Continue reading

Want to learn about epilepsy genetics more effectively? Keep reading…

Demystify. In an earlier post, Ingo blogged about the exciting new Genetic Literacy series that should appear in Epilepsia later in 2014. When we first had the idea at the International Epilepsy Congress in Montreal, we conceived of the Genetic Literacy series as a practical learning resource for practising clinicians and healthcare professionals. We really want to use this opportunity to demystify epilepsy genetics and make this information accessible and useful to readers. Continue reading

Building the Epilepsiome

Wireframe. In this post you will learn about our plans for the Epilepsiome database that is envisioned by the ILAE Genetics Commission. This knowledge database will curate information on epilepsy and genes. Also, it should be up-to-date and written in a straightforward “this is what you must know” style. Basically, the website that you want to go to if you need an update on a given gene or syndrome. But how do you get started on a project like this? Let me start by telling you what a wireframe is. Continue reading

Three reasons why we need a new genetic literacy to understand epilepsy

ILAE Genetic Commission weekly. As you might already know, Beyond the Ion Channel has become the official blog of the Genetics Commission of the International League Against Epilepsy. Starting with this post, we would like to publish a weekly post about the issues relevant to what the ILAE-GC does. We’ll kick off this new segment by telling you about the reasons behind the Genetic Literacy Series that is currently in the works. This series of 10 papers will appear this year and next in Epilepsia. Continue reading