Distal Hereditary Motor Neuropathy With SIGMAR 1 Mutation: 2 Cases at Fann University Hospital, Dakar, Senegal

Introduction: Distal hereditary motor neuropathies (dHMN) constitute a rare heterogeneous group of disorders characterized by degeneration of the motor component of peripheral nerves. Their clinical and electrophysiological presentation is very variable due to the genetic heterogeneity of these latter. Among the rare autosomal recessive forms of dHMN, mutations in the SIGMAR1 gene have recently been described and are responsible for variable phenotypes. Below, we describe the clinical, electrophysiological, and genetic features of two patients with dHMN linked to a mutation in the SIGMAR1 gene. Observations: The two patients, aged 15 and 19 at consultation, exhibited distal limb weakness beginning at ages 9 and 10, with progressive worsening that initially affected the lower limbs and later involved the upper limbs. The second patient had a first-degree consanguinity. Clinical examination revealed pes cavus in the first patient and equinovarus feet (in the second). Both showed distal motor deficits in the lower limbs without sensory involvement. Neurography showed very reduced or nearly absent motor response amplitudes in both cases, with preserved sensory potentials. Needle EMG revealed a pattern of chronic denervation Our two patients benefited from a whole exome sequencing from the DNA extracted from whole blood and the same genetic variant (variant c.580C>T) was identified homozygotically in the SIGMAR1 gene (genomic position 9:34635721 based on the reference genome version GRCh37). Given the autosomal recessive mode of transmission, genetic counseling was offered to affected families, informing them of the 25% risk of transmitting the causal mutation to their offspring. Conclusion: dHMN is a rare condition, and cases caused specifically by mutations in the SIGMAR 1 gene are even more uncommon. Since only a few patients with this mutation have been described in scientific literature, it is difficult to know exactly what phenotypes are linked to it. To improve our understanding, it xould be helpful to conduct more genetic studies and identify additional cases, which would add valuable information to what is already known.