Inherited peripheral neuropathies: Charcot-Marie-Tooth disease

Charcot-Marie-Tooth disease (CMT) refers to a spectrum of inherited peripheral neuropathies. They affect approximately one in 2500 people, and are one of the most common inherited neurological disorders. The genetic mutations follow autosomal dominant, recessive, and X-linked inheritance patterns, and spontaneous mutations also occur. CMT has been divided into two broad forms based on electrophysiological and morphologic criteria, with demyelinating forms associated with slow conduction velocities and axonal forms with normal or mildly slowed conduction velocities. However, this likely represents an oversimplification as genotyping reveals overlap in conduction velocities in some families. The clinical features of CMT follow a length-dependent pattern with distal weakness and sensory loss and reduced or absent reflexes. Some patients may be minimally affected, obscuring a familial pattern without a high index of suspicion. The discovery of new mutations has focused on physiologic mechanisms, but a clear understanding of pathologic mechanisms has remained elusive. At this time there is no effective treatment for CMT.