Potassium. The channelopathies are the largest group of genetic epilepsies, and disease-causing variants in genes for neuronal sodium channels, calcium channels, and potassium channels are among the most common causes of genetic epilepsies. However, amongst the various ion channel families, potassium channels stand out due to sheer number. There are more than 70 potassium channel genes encoded in the human genome, and the combination of various subtypes and auxiliary units generates an enormous combinatorial potential. In a recent publication, de novo variants in KCNA6, the gene for the voltage-gated potassium channel Kv1.6, were identified in childhood-onset neurodevelopmental disorders. Here is the somewhat unusual story of the most recent potassium channel gene implicated in human epilepsy. Continue reading
Tag Archives: KCNA2
The many faces of KCNA2: a 2017 update
KCNA2. We have previously discussed KCNA2 and that pathogenic variants in this gene can lead to a spectrum of neurological phenotypes. Pathogenic KCNA2 variants were first recognized in individuals with early-onset developmental and epileptic encephalopathies and have subsequently been found also in individuals and families with hereditary spastic paraplegia, episodic ataxia, and milder epilepsies. KCNA2 encodes the Kv1.2 potassium channel, a delayed rectifier class of potassium channel that enables neuronal repolarization after an action potential. A new study by Masnada and colleagues provides clinical and functional data from 23 patients, representing the largest KCNA2 cohort reported to date. Within the KCNA2-related encephalopathy spectrum, it now seems that there may be three distinct phenotypes. Continue reading
KCNA2 – an epilepsy gene in hereditary spastic paraplegia
HSP. I have to admit that the hereditary spastic paraplegias are not mentioned all that frequently on our blog. The main reason is that there is little overlap between early-onset epilepsies and adult-onset progressive neurodegenerative conditions that are characterized by spasticity and weakness in the lower extremities. In a recent publication, we described an epilepsy gene that became an HSP gene, showing an unusual overlap between both groups of conditions and establishing a novel mechanism in HSP pathogenesis. Here is a continuation of the KCNA2 story. Continue reading
SCN1A and Dravet Syndrome – your questions for the Channelopathist
Comments. After posting our 2015 update on what you should know about SCN1A, we received a number of comments on our blog and by email. We usually have the policy to respond to every comment individually. However, after we had realized that we had fallen behind with a few replies for several weeks, we felt that it might be worthwhile rephrasing some of the questions as general topics to write about, especially since many of your questions raised interesting points. Here are the questions that you asked regarding SCN1A and Dravet Syndrome. Continue reading
The two faces of KCNA2 – a novel epileptic encephalopathy
Delayed rectifier. The discovery of de novo mutations in ion channel genes as a cause for genetic epilepsies continues. In a recent publication in Nature Genetics, we have identified de novo mutations in KCNA2 as a novel cause of epileptic encephalopathies associated with ataxia. Interestingly, even within a single gene, two different phenotypes seem to be emerging. Continue reading
