EMR. When we consider the natural history of rare diseases like the genetic epilepsies, we typically think about a lack of longitudinal data that contrasts with the abundant genetic information that is available nowadays – the so-called phenotyping gap. We typically suggest that we need to obtain this information in future prospective studies to better understand long-term outcome, response to medications, and potential early warning signs for an adverse disease course. However, a vast amount of clinical data is collected on an ongoing basis through electronic medical records (EMR) as a byproduct of regular patient care. In a recent study, our group built tools to mine the electronic medical records to assess the disease history of 658 individuals with known or presumed epilepsies using clinical information collected at more than 62,000 patients encounters across more than 3,200 patient years. Here is a brief summary of our first study on EMR genomics, an untapped resource that has the potential to improve our understanding of the genetic epilepsies. Continue reading
Category Archives: SLC6A1
The genetics of Doose Syndrome or Myoclonic Astatic Epilepsy
MAE. There are many distinct childhood epilepsy syndromes that we have become critically aware of in the genomic era as they are linked to prominent genetic causes, including Dravet Syndrome (SCN1A) and Epilepsy of Infancy with Migrating Focal Seizures (KCNT1). However, there are many other epilepsy syndromes where a genetic cause has long been suspected, but has remained elusive. One of the epilepsy syndromes that has largely remained unexplored is Doose Syndrome, also referred to as Myoclonic Astatic Epilepsy (MAE) or Epilepsy with Myoclonic-Atonic Seizures. In a recent study in Epilepsia, we explored the genetic architecture of Doose Syndrome and identified monogenic causes in 14% of individuals, including SYNGAP1, NEXMIF (KIAA2022), and SLC6A1. Our study suggests that Doose Syndrome is genetically heterogeneous, possibly with a distinct genetic landscape. Continue reading
SLC6A1 – a generalized epilepsy phenotype emerging
GAT1. When we first identified SLC6A1 in 2015, we were surprised that a significant proportion of patients with disease-causing variants in this gene had a rare epilepsy phenotype referred to as Myoclonic Astatic Epilepsy (MAE). Typically, at the time of gene discovery, it is often unclear how far the phenotypic spectrum expands. In a recent publication in Epilepsia, we reviewed the phenotype of 34 patients with SCL6A1-related epilepsy. Surprisingly, in contrast to many other epilepsy genes that showed a broad and occasionally non-specific phenotypic range, the SLC6A1-related phenotype expands beyond MAE, but remains centered around generalized epilepsies with a predominance of absence seizures and atonic seizures. It is a gene that has started to write its own story. Continue reading
