Understanding the SCN2A mystery – therapeutic responses in a heterogeneous disease

Heterogeneity. The diversity of clinical presentations and responses to anti-epileptic drugs (AEDs) has posed a major obstacle in developing strategies to treat patients with SCN2A-related epilepsies. While the literature provides multiple examples of single case reports with favorable responses to various AEDs, the broad range of disease presentations and known or presumed effects on channel function has made it extremely difficult to extrapolate findings from one patient to another. In a recent publication in Brain, we reviewed the largest cohort of patients with SCN2A-related neurodevelopmental disorders so far, including a subset of patients with detailed phenotypic data over time. With this data, we were able to find support for the hypothesis that age of seizure onset correlates with the functional effect of the mutations and the response to common anti-epileptic medications, taking a first step towards understanding the SCN2A mystery. Continue reading

Five things I learned about SCN2A in Chicago

SCN2A. Last Thursday, I hopped on a plane to Chicago to join the first FamilieSCN2a Foundation Conference. SCN2A, one of the most common genes in genetic epilepsies, has emerged as a gene with a broad range of phenotypes, which makes understanding this gene relatively complicated. I am very happy that the SCN2A community is currently coming together to provide a platform for patient initiatives and connections to clinicians and researchers. Here is my list of five things I learned about the genetic shape-shifter in Chicago. Continue reading

Three novel aspects about epilepsy gene panels

Gene panels. Epilepsy gene panels have emerged as the first line genetic test for most suspected genetic epilepsies. Gene panels for childhood epilepsies are among the most common genetic tests ordered in a pediatric setting. While the role of gene panel testing is well established, the ideal design of gene panels remains an ongoing issue. A recent publication in the Journal of Medical Genetics provides additional evidence for the role of gene panel analysis in patients with genetic epilepsies. There are three aspects of this study that are particularly noteworthy. Continue reading

SCN2A – a 2016 update

The story of SCN2A. Pathogenic SCN2A variants were first described in patients with autosomal dominant benign familial neonatal/infantile seizures (BFNIS) in the early 2000s. More recently, it has became clear that variants in SCN2A can cause a wider spectrum of epilepsy phenotypes, ranging from milder phenotypes, such as BFNIS, to severe phenotypes, such as infantile spasms and severe early onset epileptic encephalopathies, including Ohtahara syndrome and West syndrome. In addition, SCN2A variants have been identified in a small number of patients with autism, schizophrenia, and intellectual disability without seizures. Despite now having earned its title as a well-established epilepsy gene, we still have a lot to learn about SCN2A. Keep reading to learn more about the expansion of the SCN2A-associated epilepsy phenotype and other recent discoveries about SCN2A. Continue reading

Here are 5 quick free web-based tools for gene interpretation

Exome rounds. Interpreting genetic variants is one of the main challenges in genomic medicine. Many people have perceived barriers to starting some of the variant analysis themselves, given that there is the widespread notion that this requires expert bioinformatics knowledge. However, this is somewhat a concept of the past. There are some beautiful and simple tools online that you can use for free. Here are my favorite web-based tools for variant interpretation. Continue reading