Expanding the genetic and phenotypic relevance of KCNB1 variants in developmental andepileptic encephalopathies: 27 new patients and overview of the literature

Developmental and epileptic encephalopathies (DEE) refer to a heterogeneous group of devastating neurodevelopmental disorders. Variants in KCNB1 have been recently reported in patients with early-onset DEE. KCNB1 encodes the alpha subunit of the delayed rectifier voltage-dependent potassium channel K(v)2.1. We review the 37 previously reported patients carrying 29 distinct KCNB1 variants and significantly expand the mutational spectrum describing 18 novel variants from 27 unreported patients. Most variants occur de novo and mainly consist of missense variants located on the voltage sensor and the pore domain of K(v)2.1. We also report the first inherited variant (p.Arg583*).