Exploring the Phenotypic Spectrum of KCNB1: A Case Series of Two Unique Presentations

Background and Purpose: We present two cases exemplifying the broad phenotypic spectrum associated with pathogenic changes in KCNB1 protein. Our case series highlights the variability of the outcomes of this genetic condition. Methods: This is a descriptive retrospective review of medical histories of two patients under the age of 18 years with KCNB1 related neurodevelopmental disorder. We performed a literature review from published articles in PubMed indexed journals. Brief Report: A 9-year-old girl with developmental delay and autism found to have a pathogenic mutation in the KCNB1 gene presented with regression in her language, staring spells, and EEG findings suggestive of Electrographic Status Epilepticus in Sleep (ESES). She is maintained on Clobazam and continues to make gains in her milestones. A 16-year-old boy with a heterozygous mutation in the KCNB1 gene presented with mild intellectual disability and attention deficit hyperactivity disorder. His EEG showed frequent bursts of generalized, sharply contoured theta activity - a finding of uncertain clinical significance. However, no clinical seizures were mentioned. He is maintained on valproic acid for mood stabilization. Conclusion: The phenotype associated with KCNB1-related neurodevelopmental disorders is variable and includes epilepsy, intellectual disabilities, and psychiatric diagnoses. While our first patient had typical manifestations of the condition, treatment with anti-seizure medication was seen as beneficial. Our second patient had no clinical seizures, and his case highlights the importance of assessing the risk-benefit ratio of anti-seizure medication. It is important to understand the spectrum of the disease in order to identify clinical manifestations and perform early testing for a better prognosis.