Statistical Shape Modeling Characterization of Cavovarus Deformity Between Demyelinating and Axonal Subtypes of Charcot-Marie-Tooth Disease.

Background: Charcot-Marie-Tooth disease (CMT) is an inherited peripheral neuropathy that is associated with a cavovarus foot deformity that leads to impaired mobility and pain. Structural differences in the hindfoot, midfoot, and forefoot that contribute to this cavovarus deformity have not been fully characterized or described between disease subtypes. This study aimed to identify structural differences in the foot associated with CMT and between demyelinating and axonal subtypes in a retrospective cross-sectional study.

Methods: In this study, we use statistical shape modeling, a mathematical tool to describe morphologic averages and variation to create a 14-bone model of the tibia through metatarsals from retrospectively identified weightbearing computed tomography (WBCT) images from individuals with CMT and controls, classified as having either demyelinating or axonal disease. We used a Hotelling T² test and a principal components analysis followed by statistical tests to identify significant differences in morphology between CMT and control groups and between demyelinating, axonal, and control groups.

Results: Results of this analysis showed similarity in the overall foot deformity between subtypes and supported previous research on foot alignment by highlighting several regions of the foot and ankle with an alignment-driven deformity. Differences in overall cavovarus position were identified between CMT and control groups, with additional increase in hindfoot varus rotation seen in the demyelinating group. Along each component of the deformity, the demyelinating group demonstrated more severe deformity than the axonal group.

Conclusion: There are differences in foot morphology throughout the hindfoot, midfoot, and forefoot that contribute to the cavovarus deformity seen in CMT. Demyelinating CMT presents with severe global deformity with pronounced hindfoot varus while axonal CMT has a more midfoot-centered deformity.

Clinical relevance: These results demonstrate the importance of disease subtype in treatment planning for individuals with CMT-related cavovarus deformity and support the use of 3-dimensional imaging in characterization of cavovarus foot structure.