Co-Occurrence of and Variants in a Patient With Paroxysmal Extreme Pain Disorder, Contradictory Analgesia, and Intractable Paroxysmal Non-Kinesigenic Dyskinesia.
Gain-of-function mutations in , encoding the voltage-dependent Nav1.7 sodium channel, cause three autosomal-dominant disorders associated with severe pain: primary erythromelalgia, paroxysmal extreme pain disorder (PEPD), and small fiber neuropathy. On the other hand, biallelic loss-of-function mutations have been linked to impaired pain perception. Notably, the coexistence of both hyperalgesia and hypoalgesia within the same patient harboring the I234T variant has been reported in three independent patients to date. We report a 7-year-old girl harboring co-occurring (I234T) and variants who presented with paroxysmal extreme pain disorder, contradictory analgesia, sensitivity to heat, and intractable head-drop attacks. Based on the genetic and clinical analyses, she was diagnosed as having PEPD and -related paroxysmal dyskinesia. The intractable head-drop attacks were considered as paroxysmal non-kinesigenic dyskinesia. In addition, she exhibited easy fatigability and hypotonia. Taken together with her cold, cyanotic feet, these findings suggest that she may have also had small fiber neuropathy.