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

Retiring the word “mutation” in clinical practice

Mutation. What images does the word conjure up for you? Genetic counselors have long avoided using this term in clinical practice due to its similarity to the word “mutant”, favoring instead the vague but people friendly term “changed gene”. In fact, there is a far more scientific reason for clinicians to avoid using the term “mutation”, and that is the definition of the word itself.  Continue reading

What’s new with KCNT1 – a 2016 update

Continued expansion of the KCNT1 phenotype. In 2012, de novo heterozygous KCNT1 variants were first described in six individuals with migrating partial seizures of infancy (MPSI) (Barcia et al, 2012). In the same edition of Nature Genetics, Heron and colleagues (2012) described 3 families with frontal lobe epilepsy with prominent psychiatric features were also identified to have heterozygous disease-causing variants in KCNT1. Within the last 5 years, de novo and inherited heterozygous KCNT1 variants have been found in a number of patients with MPSI and ADNFLE. Yet, there have been no clear genotype-phenotype correlations established. Recently, several studies have identified KCNT1 variants in patients with other types of epilepsy. Keep reading to learn more about the expansion of the KCNT1-associated epilepsy phenotype. Continue reading

What’s new with SCN8A – a 2016 update

An unexpected twist in the SCN8A story. SCN8A mutations were first implicated in epilepsy in 2012, when a de novo missense variant was identified in a patient with early infantile epileptic encephalopathy (EIEE) via genome sequencing. Since then, a number of patients with de novo heterozygous SCN8A variants and epilepsy have been reported, firmly establishing the role of SCN8A in EIEE, and we have learned a lot about the associated phenotype, mutation spectrum and disease mechanism within the last four years. Recently, a heterozygous familial SCN8A missense variant was identified in several families with a significantly milder epilepsy phenotype than reported in previous patients. Read further to learn more about the expanded SCN8A-associated epilepsy phenotype. Continue reading

STXBP1 – your questions for the Channelopathist

Controversy. Our recent post that featured our Neurology publication on STXBP1 generated much interest, discussion, and debate. In particular, we received feedback from the online STXBP1 parent community that our assessment of STXBP1 encephalopathy as a static rather than a degenerative disease may be incomplete. Let me try to reconcile the results of our study with the experiences that families have shared with us in the last two weeks, trying to understand how STXBP1 can be a disease with many faces and what the common features are. Continue reading