Parkinsonism and Charcot-Marie-Tooth neuropathy type 2P in a French patient with LRSAM1 pathogenic variation.

Fiche publication

Date publication

juillet 2025

Journal

European journal of medical genetics

Auteurs

Membres identifiés du Cancéropôle Est :
Pr VERGER Antoine

Tous les auteurs :
Ducatel P, Verger A, Selton M, Renaud M, Puisieux S, Grosset A, Hopes L, Michaud M

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/40721190

Résumé

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. 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.