Finally, biallelic null mutations, whether from nonsense mutations or missense mutations with no detectable sodium current, are lethal in utero or at birth.8 In hindsight, this paradigm suggests the original report of SCN4A-associated CMS was indeed caused by a recessive compound heterozygote (p.S246L/p.V1442E).5 Because the fast-inactivation defect for p.V1442E was much greater (−33 mV shift) than for p.S246L (−7.3 mV), we initially considered p.S246L to possibly be a benign polymorphism. This evidence concerns the gene SCN4A and congenital myasthenic syndrome.