Background: The KCNMA1 gene encodes the α-subunit of the large conductance, 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 large family with generalized epilepsy and paroxysmal nonkinesigenic dyskinesia. Recent research has established homozygous KCNMA1 mutations accountable for the phenotype of cerebellar atrophy, developmental delay, and seizures.
Case report: Here, we report the case of a patient with a novel homozygous truncating mutation in KCNMA1 (p.Arg458Ter) presenting with both the loss- and gain-of-function phenotype with paroxysmal dyskinesia, epilepsy, intellectual delay, and corticospinal–cerebellar tract atrophy.
Conclusion: This report extends the KNCMA1 mutation phenotype with a patient who carries a novel frameshift variant, presenting with both the gain- and loss-of-function phenotypes along with spinal tract involvement as a novel characteristic.
Keywords: Cerebellar atrophy, dyskinesia, epilepsy, KCNMA1, spinal tract atrophy.