If there are large numbers of patients with hereditary sensory-motor neuropathies (or CMT for Charcot-Marie-Tooth disease), it is not the same for the « pure motor » forms, also known as of spinal CMT or Distal hereditary motor neuropathies (dHMN). These forms are autosomal recessively or dominantly inherited and are due to mutations in less than 20 genes (including the recently implicated SORD gene). High-throughput sequencing of these genes accelerated the search for correlations between genotypes and phenotypes.
Two articles published in December 2020 illustrate these advances. The first one, from a Spanish consortium, reports data from 163 patients from 108 families with dHMN. The diagnostic yield was 29% for the 108 families, the HSPB1, GARS1, BICD2 and DNAJB2 genes being the most frequently mutated.
In the other publication, from China, and on a smaller sample (24 families), the diagnostic yield was found to be exactly the same (29%), with a gene distribution being slightly different. In both studies, the role of the SORD gene, usually responsible for autosomal recessive forms, is emphasized. The relatively low diagnostic yield suggests that many more dHMN genes remain to be discovered.