Expanding the Phenotype of Homozygous KCNMA1 Mutations; Dyskinesia, Epilepsy, Intellectual Disability, Cerebellar and Corticospinal Tract Atrophy

Abstract

Background: The KCNMA1 gene encodes the α-subunit of the largeconductance, voltage, and calcium-sensitive potassium channel(BK channels) that plays a critical role in neuronal excitability.Heterozygous mutations in KCNMA1 were first illustrated in a largefamily with generalized epilepsy and paroxysmal nonkinesigenicdyskinesia. Recent research has established homozygous KCNMA1mutations accountable for the phenotype of cerebellar atrophy,developmental delay, and seizures.Case Report: Here, we report the case of a patient with a novelhomozygous truncating mutation in KCNMA1 (p.Arg458Ter)presenting with both the loss- and gain-of-function phenotype withparoxysmal dyskinesia, epilepsy, intellectual delay, and corticospinal–cerebellar tract atrophy.Conclusion: This report extends the KNCMA1 mutation phenotypewith a patient who carries a novel frameshift variant, presenting withboth the gain- and loss-of-function phenotypes along with spinal tractinvolvement as a novel characteristic.