Purpose of review: This review focuses on recent advances in the diagnostic approaches and the underlying pathophysiological mechanisms of Charcot-Marie-Tooth (CMT) disease. We also discuss the emerging therapies for this hereditary neuropathy.
Recent findings: To date, numerous genes are implicated in CMT, and new genes have recently been found to be associated with this neuropathy (INF2, FBLN5, etc.). Some specific or evocative clinical signs of CMT subtypes (proteinuria with INF2 mutations, etc.) have been identified. Characteristic pathological findings, which may suggest gene mutations, are also recognized by nerve biopsy (mainly ultrastructural lesions).
Summary: CMT disease is the most common inherited neuromuscular disorder, with a fairly homogeneous clinical phenotype (progressive distal muscle weakness and atrophy, foot deformities, distal sensory loss, and depressed tendon reflexes). With more than 40 genes implicated, an update of the present and rather confusing classification of CMT is needed. Over the last few years, new mutated genes have been discovered. Although nerve biopsy is not routinely carried out in CMT neuropathies, it may show characteristic features, which can orientate the search for the mutated gene. There are currently no effective medications for CMT, but clinical trials are ongoing or planned.