KCNT1 mutations in seizure disorders: the phenotypic spectrum and functional effects

Mutations in the potassium channel subunit gene KCNT1 have been identified during the past three years in patients with neurological disorders including nocturnal frontal lobe epilepsy, epileptic encephalopathies and white matter diseases. KCNT1 mutations have also been linked to cardiac arrhythmias. In this review we describe the current knowledge of the KCNT1 gene and its protein product. We discuss the mutational spectrum and range of disorders associated with KCNT1, KCNT1 protein function, the functional effect of KCNT1 mutations, and how this may be related to disease causation. We also discuss preliminary clinical trials of the drug quinidine as a treatment for patients with KCNT1-related disorders. Quinidine alters KCNT1 channel function and its potential use in the treatment of these disorders is an example of personalised medicine based on genetic information. (By Dr. Sarah Heron, http://jmg.bmj.com/content/early/2016/01/06/jmedgenet-2015-103508 )