Diagnosis, natural history, and management of Charcot-Marie-Tooth disease

Charcot-Marie-Tooth disease is the most common inherited neuromuscular disorder. There have been substantial advances in elucidating the molecular bases of this genetically heterogeneous neuropathy and, in most cases, molecular diagnosis is now possible. The diagnostic approach requires careful assessment of clinical presentation and mode of inheritance, nerve-conduction studies, and DNA testing, and current research is focused on assessing natural history and finding effective treatments. Disease course is variable because of genotypic and phenotypic heterogeneity. At present, there is no drug therapy for Charcot-Marie-Tooth disease, and rehabilitation therapy and surgical procedures for skeletal deformities are the only available treatments, although best practice has not been defined. Animal models are proving useful for the identification of therapeutic targets and approaches. Progesterone antagonists, neurotrophic factors, ascorbic acid, and curcumin have shown promising results in experimental models, and ascorbic acid is being studied in large randomised controlled trials.