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Background: Mutations in SCN4A may lead to myotonia. Methods: Presentation of a large family with myotonia, including molecular studies and patch clamp experiments using human embryonic kidney 293 cells expressing wild-type and mutated channels. Results: In a large family with historic data on seven generations and a clear phenotype, including myotonia at movement onset, with worsening by cold temperature, pregnancy, mental stress, and especially after rest after intense physical activity, but without weakness, the phenotype was linked with the muscle sodium channel gene ( SCN4A ) locus, in which a novel p.I141V mutation was found. This modification is located within the first transmembrane segment of domain I of the Na v 1.4 α subunit, a region where no mutation has been reported so far. Patch clamp experiments revealed a mutation-induced hyperpolarizing shift (−12.9 mV) of the voltage dependence of activation, leading to a significant increase (approximately twofold) of the window current amplitude. In addition, the mutation shifted the voltage dependence of slow inactivation by −8.7 mV and accelerated the entry to this state. Conclusions: We propose that the gain-of-function alteration in activation leads to the observed myotonic phenotype, whereas the enhanced slow inactivation may prevent depolarization-induced paralysis.

Cortical plasticity of the human brain permits functional recovery after brain injury even in the absence of neuronal recovery. We report the combined evaluation, including electrophysiology and functional magnetic resonance imaging, of the pattern of cortical and cerebellar reorganization, in a patient with mirror movements as a sequel of perinatal unilateral brain injury. Recovery resulted in motor control by the healthy hemisphere using direct ipsilateral corticospinal projections and the contralateral cerebellum.