Charcot-Marie-Tooth disease

Charcot-Marie-Tooth (CMT) disease, also known as hereditary motor and sensory neuropathy (HMSN), is the most commonly inherited neuropathy of lower motor (to a lesser degree sensory) neurons.

Clinical presentation

Signs and symptoms usually become first evident in childhood. Typically this starts in the lower limbs with weakness, atrophy and deformity, and later affects the upper limbs. It rarely involves the more proximal musculature and rarely involves the cranial nerves. Sensory changes are present but usually to a lesser degree.

Pathology

It is not a single condition, but a cluster of heterogeneous mutations with many subtypes, classified by which gene is affected. As expected the number and classification is in flux. Most frequently it is autosomal dominant in inheritance (although this is variable).

Classification

• CMT type 1
  • this form of CMT disease is a disorder of peripheral myelination
  • repeated cycles of demyelination and remyelination result in a thick layer of abnormal myelin around the peripheral axons
  • these changes cause what is referred to as an onion bulb appearance
• CMT type 2
  • this primarily is a neuronal (i.e. axonal) disorder, not a demyelinating disorder. CMT type 2 results in peripheral neuropathy through direct axonal death and Wallerian degeneration
• CMT type 3 (also known as Déjerine-Sottas disease)
  • characterized by infantile onset, this condition results in severe demyelination with delayed motor skills; it is much more severe than type 1
• CMT X (X-linked CMT) and CMT 4: these are also demyelinating neuropathies

Radiographic features

The nerve roots are typically hypertrophic with onion bulb sign. This represents hypertrophic demyelination. Denervation changes in muscles are apparent.

Some enhancement may be seen on MRI, but it is not usually a prominent feature.

History and etymology

It is named after Jean-Martin Charcot, Pierre Marie and Howard Henry Tooth.