This case report illustrated that (1) phenotypic heterogeneity in PEPD is greater than previously appreciated, notably in terms of clinical trajectory and therapeutic response to conventional treatment, (2) early genetic diagnosis is critical in avoiding potential opioid spirals and facilitating family planning and cascade testing, and (3) selective Nav1.7 antagonists currently in clinical development may offer hope for refractory cases. Here, SCN9A is linked to paroxysmal extreme pain disorder.