The KCNB1 gene encodes the pore-forming and voltage-sensing β subunit of the voltage-gated potassium (K+) channel subfamily 2 (Kv2.1) that is expressed throughout the brain and plays essential roles in regulating neuronal excitability, contributing to action potential repolarization and dynamic modulation of neuronal activity.
These channels are found primarily in the brain where they transport potassium ions out of neurons.
Pathogenic variants that affect the KCNB1 potassium channel impair the flow of potassium ions in the brain. In most cases, the KCNB1 mutation leads to decreased activity of the affected ion channel. Changes in the flow of potassium ions in the brain causes epilepsy and associated developmental disorders.
KCNB1-related disorder is inherited in an autosomal dominant pattern.
In most individuals with KCNB1-related disorders, the pathogenic KCNB1 variant occurred spontaneously (de novo). In rare cases, the pathogenic KCNB1 variant has been passed on from an asymptomatic parent due to parental mosaicism.
The diagnosis of KCNB1 encephalopathy is made by molecular genetic testing. This is usually done with an epilepsy gene panel looking at a number of genes associated with epilepsy or by whole exome sequencing.
To date, more than 50 mutations has been reported.