Charcot-Marie-Tooth disease (CMT) is one of the most common hereditary neuropathies. Very heterogeneous from a clinical and electrophysiological point of view, but also genetically (nearly a hundred known genes, all forms included), CMT causes a distal motor deficit predominant in the muscles of the feet and hands. In later onset forms, especially in the elderly, the diagnosis is often difficult because other causes, not hereditary, may be involved.
In an article published in November 2020, European clinicians and geneticists have focused in this population on the subgroup of axonal forms of CMT but also on a particular gene, the MME gene, recently implicated in this age group and which encodes a metalloprotease called neprilysin. Two hundred and thirty patients with axonal forms of neuropathy which began after the age of 35, benefited from a genetic study, either in whole exome (126 patients) or exclusively targeting the MME gene (104 patients). As expected, the diagnostic performance of the whole exome was quite disappointing, with 18% of cases having a mutation in genes for CMT or other hereditary neuropathies. Among the resolved cases, the MME gene was frequently involved (1/3 of cases). Mutations in this gene can give rise to both autosomal recessive and autosomal dominant forms, the former being more serious. Therefore the implication of this gene should be investigated as a priority in late-onset forms of CMT.
