Macrodactyly of the foot resulting from plantar nerve impairment

The role of the plantar nerve in the pathogenesis of macrodactyly of the foot is unknown. We investigated the distribution of affected toes and forefoot in 27 feet of 26 patients with pedal macrodactyly, and how this relates to innervation of the affected plantar nerve. A preoperative ultrasound examination was performed to determine the diameter and structure of the plantar nerve. Histologic findings were recorded during surgery. The microstructure of affected plantar nerves was evaluated by hematoxylin-eosin staining, while S100 expression was assessed by immunofluorescence analysis. Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) gene mutation in the affected nerve tissue was detected by Sanger DNA sequencing. The affected toes and forefoot involved innervation of the medial plantar nerve in 25/27 feet, the lateral plantar nerve in one foot, and both medial and lateral plantar nerves in one foot. All affected plantar nerves, which were accompanied by a fatty strip, were surrounded by or infiltrated with fat. The affected plantar nerves showed enlargement, a tortuous course, fatty infiltration, or a combination of these. Pathologic changes in affected plantar nerves involved only the epineurium and not the perineurium or endoneurium. Expression of the Schwann cell marker S100 was absent in some areas of affected nerves. Sequencing of PIK3CA exons identified a gain-of-function mutation (p.His1047Arg) in affected plantar nerves. These results indicate that pathologic impairment of the plantar nerve can lead to macrodactyly of the foot, which may be considered as a nerve trunk disease.