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.
