Mechanisms underlying a life‐threatening skeletal muscle Na+ channel disorder

Non-technical summary Non-dystrophic myotonias are rare disorders of skeletal muscle that are characterized by delayed relaxation of the muscle force or increased muscle contraction. These disorders result from genetic defects in sodium and chloride channels that are expressed in the muscle fibres. We describe here the functional consequences of a defect that has been identified in a severe form of myotonia that was lethal in newborn babies. We show that the affected skeletal muscle sodium channel protein, called Nav1.4, has an exacerbated activity that may well lead to muscle hyperexcitability in the reported patients. We strongly recommend treating patients with severe neonatal episodic laryngospasm with sodium channel blockers as soon as the diagnosis has been established.