Further delineation of LRSAM1-related Charcot-Marie-Tooth type 2P with parkinsonism.

Abstract

LRSAM1 pathogenic variations are linked to an axonal motor and sensory polyneuropathy known as Charcot-Marie-Tooth disease type 2P, but extra peripheral neurologic impairment is suspected. We report a patient with CMT2P and parkinsonism. We describe a 66-year-old man presenting with pes cavus, gait instability, and mild distal motor weakness. Nerve conduction studies revealed sensory-motor axonal neuropathy consistent with CMT2P. After several months, he developed lower-limb and right upper-limb hypertonia, jerky eyes, and hypomimia. ¹²³ I-FP-CIT single-photon emission computed tomography revealed bilateral alteration of the presynaptic dopaminergic pathway, especially regarding the putamen. The full CMT panel confirmed a heterozygote pathogenic variant (NM_001005373.4: c.2093_2104del, p.(Gln698_Gln701del)) in the LRSAM1 gene. To the best of our knowledge, this is the seventh clinical description linking an LRSAM1 pathogenic variant and parkinsonism. Consequently, we believe that patients with parkinsonism and sensorimotor axonal neuropathy should be explored for LRSAM1 mutation.