Charcot-Marie-Tooth disease

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

It is not a single condition, but a cluster of heterogenous mutations with many sub types, 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), with sign and symptoms usually becoming 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.

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.

The disease is divided into the following types:

• 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 (ie, 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 Dejerine-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.

Etymology

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