Modifier genes in Dravet Syndrome: where to look and how to find them

Converging thoughts. During late 2013, I had several unrelated discussions about the possible role of genetic modifiers of SCN1A in Dravet Syndrome. To some extent, SCN1A is a paradox. One the one hand, the connection between Dravet Syndrome and SCN1A is one of the clearest connections between gene and disease that we see in genetic epilepsies. On the other hand, we see a remarkable phenotypic heterogeneity in families, and some presumably pathogenic SCN1A variants can also be identified in unaffected control individuals. This leaves us with the question whether there are genetic modifiers in Dravet Syndrome that might help provide some insight into additional mechanisms of disease. This post is a collection of 10 individual thoughts that emerged during the discussions last year. Continue reading

The genetics of treatment response in newly diagnosed epilepsy

Two questions. There are two main questions that we would like to answer with genetics in the field of epilepsy. First, are there genetic risk factors for epilepsies and if so, what are they? Secondly, are there genetic factors that help us understand how patients react to treatment, i.e. are there genes that predispose to response to antiepileptic drugs or that might be associated with side effects? While we have made much progress in answering the first question by identifying many epilepsy genes, there have been few answers for the second question, the field of pharmacogenomics. Now, a recent study in Human Molecular Genetics looks at potential genetic risk factors for the response to antiepileptic drugs in newly treated epilepsy. This is a study that needed to be performed and that we were waiting for. Continue reading