Charcot-Marie-Tooth disease (CMT) is a genetically and clinically heterogeneous polyneuropathy characterized by progressive motor and sensory deficits. It is one of the most common inherited causes of neuropathy. Symptoms of weakness in the limbs and sometimes the hands are often first noted in late childhood or early adulthood. It may be accompanied with mild to moderate sensory loss and sometimes neuropathic pain. There is usually some atrophy of small muscles in the hands and feet. Deep tendon reflexes are often depressed, and it is common for pes cavus (a fixed plantar flexion, ie, the arch of the foot does not flatten when bearing weight) and hammer toes to develop. Several dominant forms of CMT are related to mutations in a tRNA synthetase and activation of a integrated stress response.
CMT can be subdivided into two large groups on the basis of electrophysiologic criteria: CMT1 is the demyelinating form and CMT2 the axonal form. Patients with primarily distal motor neuropathy are sometimes considered to comprise a third type. Nerve conduction velocity is reduced and electromyography can also be diagnostically helpful. It may be helpful to look for characteristic changes such as loss of myelinated fibers and the presence of focal myelin sheath folding in sural nerve biopsies.
Early-onset glaucoma, optic atrophy, and sensorineural hearing loss are found in some families. Dementia and intellectual deficits are not generally a part of CMT.
ICD10CM: G60.0 – Hereditary motor and sensory neuropathy
SNOMEDCT: 398100001 – Hereditary motor and sensory neuropathy
Differential Diagnosis & Pitfalls
Various features of CMT may be mimicked by other disorders. The hereditary motor neuropathies do not have sensory features, while the hereditary sensory neuropathies usually have few motor symptoms. Sporadic disease in individuals without a family history is more likely to have a neuropathy due to inflammation or infections. HIV, syphilis, an occult neoplasm, vitamin deficiency (eg, thiamine), or metal intoxication may have an associated neuropathy. Diabetes mellitus and alcohol use disorder must be ruled out.