Anti-KCNA1 monoclonal antibody

We report on the case of a 10-year-old Iraqi Kurdish boy who developed recurrent short-lived attacks of severe instability of stance and gait, vertigo, nausea, and vomiting. Examination revealed peri-oral myokymia. Histories of fever, head trauma, seizures, migraine, or illicit drug abuse were not obtained. Needle electromyography revealed myokymic discharges. KCNA1 missense G1210A genetic mutation was found. The boy's parents and grandparents did not harbour this mutation. The patient had sporadic episodic ataxia type 1 and acetazolamide was prescribed.

The nervous system maintains a delicate balance between excitation and inhibition, partly through the complex interplay between voltage-gated sodium and potassium ion channels. Because K+ channel blockade or gene deletion causes hyperexcitability, it is generally assumed that increases in K+ channel gene expression should reduce neuronal network excitability. We have tested this hypothesis by creating a transgenic mouse that expresses a Shaker-type K+ channel gene. Paradoxically, we find that addition of the extra K+ channel gene results in a hyperexcitable rather than a hypoexcitable phenotype. The presence of the transgene leads to a complex deregulation of endogenous Shaker genes in the adult central nervous system as well as an increase in network excitability that includes spontaneous cortical spike and wave discharges and a lower threshold for epileptiform bursting in isolated hippocampal slices. These data suggest that an increase in K+ channel gene dosage leads to dysregulation of normal K+ channel gene expression, and it may underlie a mechanism contributing to the pathogenesis of human aneuploidies such as Down syndrome.