Charcot-Marie-Tooth Disease (CMT)

Severe, Early-Onset CMT

What is severe, early-onset Charcot-Marie-Tooth (CMT)?

Early-onset CMT is a subtype of CMT that is a particularly severe variant of the disease. Other terms used to describe this variant include CMT3, Dejerine-Sottas disease, and congenital hypomyelinating neuropathy.

The use of the terms “Dejerine-Sottas disease” and “congenital hypomyelinating neuropathy” began prior to the identification of the genetic defects currently used to classify CMT patients into subtypes. Therefore, many of the same genes that cause other subtypes of CMT also cause these disorders; however, patients are more severely affected.

In general, the Dejerine-Sottas disease subtype is used to classify patients who have a particularly severe form of CMT with onset of the disease at early infancy. Congenital hypomyelinating neuropathy describes patients whose disease is recognized even earlier, usually during infancy.

What are the symptoms of severe, early-onset CMT?

Severe, early-onset CMT presents in infancy with hypotonia (low muscle tone), delayed motor development, prominent sensory loss, distal followed by proximal weakness, absent reflexes, ataxia, and profound slowing of nerve conduction.

For more, see Signs and Symptoms.

What causes severe, early-onset CMT?

Severe, early-onset CMT is caused by defects in the genes for proteins found in axons, fibers that carry electrical signals between the brain and spinal cord and the rest of the body, or in the genes for proteins found in myelin, a coating on axons that insulates and nourishes them. Some of these same genes, such as PMP22, MPZ, and GJB, also cause CMT1 and CMT2.

Severe, early-onset CMT can be inherited in either an autosomal dominant or recessive pattern. For more, see Causes/Inheritance .

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