Novel Biallelic PLEKHG5 Variant Associated With Intermediate Charcot-Marie-Tooth Disease: Case Report From South America

Abstract

Background and aims: Biallelic pathogenic variants in PLEKHG5 are associated with two distinct recessive phenotypes, including distal hereditary motor neuropathy AR type 4 and intermediate Charcot-Marie-Tooth disease type C (CMT). No South American cases have been previously reported.

Methods: We evaluated a male patient with suspected hereditary neuropathy using clinical, electrophysiological, and genetic studies.

Results: Symptoms began at 12 years with progressive distal weakness. At 40 years, he had foot drop, pes cavus, distal atrophy, areflexia, and sensory loss to the knees. Disability scales indicated moderate impairment. Electroneuromyography revealed abolished responses in the lower limbs and motor conduction velocities in the intermediate range (35-40 m/s). Genetic analysis identified the homozygous variant c.59G>A (p.Arg20Gln) in PLEKHG5, currently classified as VUS.

Interpretation: This reports presents a case from South American linking a homozygous PLEKHG5 variant to recessive intermediate CMT, expanding the geographic and phenotypic spectrum of PLEKHG5-related neuropathies.

Keywords: Charcot‐Marie‐tooth disease; PLEKHG5; hereditary neuropathy; intermediate CMT.