SCN9A and paroxysmal extreme pain disorder: In contrast to IE, the SCN9A mutations associated with PEPD alter Nav1.7 by impairing inactivation of the channel leading to an enhanced persistent current.44 A key unanswered question is why the Nav1.7 mutations associated with IE and PEPD cause such different phenotypic expression particularly in terms of the distal predominance of symptoms in the former and proximal in the latter.