LRSAM1-related sensory-predominant axonal neuropathy: a nationwide Japanese cohort study

Leucine-rich repeat and sterile alpha motif-containing 1 (LRSAM1) variants cause Charcot-Marie-Tooth disease type 2P (CMT2P), a rare axonal subtype of CMT, but its clinical spectrum and genotype–phenotype relationship remain incompletely defined.

This nationwide Japanese cohort and pooled analysis demonstrate clustering of pathogenic LRSAM1 variants in the C-terminal RING domain and define CMT2P as an adult-onset, slowly progressive, sensory-predominant axonal neuropathy with marked lower-limb involvement.

LRSAM1 testing should be considered in adults with axonal neuropathy showing sensory ataxia, impaired vibration sense or distal lower-limb sensory loss, even when motor weakness is mild.