The notion that dysfunction in the same ion channel can be associated in distinct paroxysmal phenotypes is already known for SCN9A. In 17 of 18 patients with SCN9A missense mutations published to date, the rectal, ocular and mandibular pain seen in PEPD does not overlap with the severe burning hand and foot pain characteristic of PE [48]. This evidence concerns the gene SCN9A and paroxysmal extreme pain disorder.