Boy in the Barrel: Excruciating Paroxysmal Pain Disorder Associated With an SCN9A Gain-of-Function Variant

Gain-of-function variants in SCN9A, encoding the Nav1.7 sodium channel, cause inherited painful neuropathic disorders. We report a young man with severe childhood-onset heat-triggered paroxysmal pain, autonomic dysfunction, skeletal abnormalities, and a de novo SCN9A p.Ile234Thr variant, emphasizing the diagnostic and therapeutic relevance of comprehensive phenotyping.

The patient developed excruciating lower-limb pain in early childhood, partially relieved by prolonged immersion in cold running water. Evaluation demonstrated marked small-fibre dysfunction, absent sympathetic skin responses, impaired sweating, absent lower-limb pain-related evoked potentials, loss of dermal and epidermal nerve fibres, pronounced small myelinated fibre loss on sural nerve biopsy, and mild large-fibre involvement. Whole-exome sequencing identified the de novo pathogenic SCN9A variant c.701 T>C; p.Ile234Thr. Carbamazepine led to more than 90% pain improvement and substantial functional recovery.

This case expands the clinical spectrum associated with SCN9A p.Ile234Thr and illustrates how genetic diagnosis may directly guide treatment. The associated large-fibre abnormalities and acetabular dysplasia are interpreted cautiously, as their relationship to SCN9A dysfunction remains uncertain.