De novo KCNB1 missense variant causing developmental and epileptic encephalopathy: Two case reports

Abstract

Rationale: Developmental and epileptic encephalopathy (DEE) defines a group of severe and heterogeneous neurodevelopmental disorders. The voltage-gated potassium channel subfamily 2 voltage-gated potassium channel α subunit encoded by the KCNB1 gene is essential for neuronal excitability. Previous studies have shown that KCNB1 variants can cause DEE. Herein, we report the cases of 2 children with DEE caused by pathogenic variants in the KCNB1 gene. Trio whole-exome sequencing identified novel KCNB1 genotypes, c. 1160C > A and c.1012C > T, which had not been reported previously, in 2 unrelated patients.

Patient concerns: Two children were admitted to our hospital for a detailed evaluation of frequent seizures. And both of these children have abnormal electroencephalogram and brain magnetic resonance imaging results, accompanied by developmental delay.

Diagnoses: A genetic study using trio-whole-exome sequencing confirmed the diagnosis of KCNB1-related developmental and epileptic encephalopathy.

Interventions: Both patients accepted the treatment of antiepileptic drugs. 1 patient had seizure remission with a combination of sodium valproate and lamotrigine, and the other was lost to follow-up.

Outcomes: Trio-whole-exome sequencing technology was used to determine the etiology of the 2 children with DEE.

Lessons: This study confirmed that genetic testing provides a basis for the diagnosis of children with abnormal electroencephalogram and brain magnetic resonance imaging findings and developmental delay, and provides data supporting a future phenotype-genotype correlation study.