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We identified a recurrent mutation in <jats:italic>KCNA2<\/jats:italic> (c.881G&gt;A, p.R294H), encoding the voltage\u2010gated K<jats:sup>+<\/jats:sup>\u2010channel, K<jats:sub>V<\/jats:sub>1.2, in two unrelated families with HSP, intellectual disability (ID), and ataxia. Follow\u2010up analysis of\u2009&gt;\u20092,000 patients with various neurological phenotypes identified a de novo p.R294H mutation in a proband with ataxia and ID. Two\u2010electrode voltage\u2010clamp recordings of <jats:italic>Xenopus laevis<\/jats:italic> oocytes expressing mutant K<jats:sub>V<\/jats:sub>1.2 channels showed loss of function with a dominant\u2010negative effect. Our findings highlight the phenotypic spectrum of a recurrent <jats:italic>KCNA2<\/jats:italic> mutation, implicating ion channel dysfunction as a novel HSP disease mechanism. 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