Exome sequencing in the rolandic epilepsies

Beyond GRIN2A. The childhood epilepsies traditionally referred to as Benign Rolandic Epilepsy (BRE) or benign epilepsy with centro-temporal spikes (BECTS) have had various names in the past, which reflects somewhat the difficulties of fully putting this group of seizure disorders into clear categories. While most presentations are relatively mild and self-limited childhood epilepsies, a sizeable fraction of these non-lesional focal epilepsies have an atypical course. The genetics of the rolandic epilepsies and the related epilepsy-aphasia spectrum are tightly linked to GRIN2A, the most prominent gene in this group of conditions. However, are there other genes? A recent publication examined the genetic basis of self-limited focal epilepsies of childhood and found interesting new candidate genes in atypical presentations. Continue reading

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

SCN3A – a sodium channel in epilepsy and brain malformations

The missing ion channel. A little more than two years ago, we wrote about our discovery of SCN3A as a novel disease gene in epileptic encephalopathies. At the time, SCN3A was the missing ion channel, the only brain-expressed voltage gated sodium channel that did not have a clear gene-disease relationship. However, since the initial discovery of SCN3A as a disease gene, both the phenotypic spectrum and variant landscape have expanded considerably. In a recent publication, we updated our knowledge based on information of 22 individuals with SCN3A-related disorders, which showed brain malformations in more than 75% of individuals and an unusual clustering of pathogenic variants in parts of the Nav1.3 channel. Continue reading

Ten steps ahead while six feet apart – telemedicine in child neurology

Telehealth. Yes, looking at my last post, this blog has been silent for a while. With the COVID-19 pandemic ongoing, it has been difficult to find a good launching point to write about genetic epilepsies again without somehow feeling that I’m missing the point with regards to the major challenges that the epilepsy genetic community is facing in 2020. But was has actually happened in epilepsy genetics in the United States during the pandemic? In parallel to the dramatic medical issues at the frontline, something very interesting has happened in the background – the shift from in-person medicine to telemedicine, including the vast majority of outpatient visits in child neurology. Telemedicine, remote healthcare services that include audio and video equipment, has long been technically feasible, but has led a niche existence due to licensing restrictions and lack of reimbursement. However, this all changed quickly during the COVID-19 pandemic. But did this transition work? Is telemedicine really as effective as suggested and were we able to provide care along the entire spectrum of disorders in child neurology, including the genetic epilepsies? In a new publication in Neurology, we analyzed more than 2,500 telehealth visits in child neurology, facilitated by a new healthcare analytics pipeline that we built in response to the challenges of the telemedicine transition. Continue reading