Clinical and electrophysiological aspects of CMT

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Neuromolecular Med. 2006;8(1-2):3-22.

Clinical and electrophysiological aspects of charcot-marie-tooth

disease.

Pareyson D, Scaioli V, M.

Division of Biochemistry and Genetics, Carlo Besta National

Neurological Institute, via Celoria, 11, 20133, Milan, Italy.

Charcot-Marie-Tooth disease (CMT) is a genetically heterogeneous

group of disorders sharing the same clinical phenotype, characterized

by distal limb muscle wasting and weakness, usually with skeletal

deformities, distal sensory loss, and abnormalities of deep tendon

reflexes.

Mutations of genes involved in different functions eventually lead to

a length-dependent axonal degeneration, which is the likely basis of

the distal predominance of the CMT phenotype. Nerve conduction

studies are important for classification, diagnosis, and

understanding of pathophysiology.

The subdivision into demyelinating CMT1 and axonal CMT2 types was a

milestone and is still valid for the majority of patients.

However, exceptions to this partition are increasing. Intermediate

conduction velocities are often found in males with X-linked CMT

(CMTX), and different intermediate CMT types have been identified.

Moreover, for some genes, different mutations may result either in

demyelinating CMT with slow conduction, or in axonal CMT. Nerve

conduction slowing is uniform and diffuse in the most common CMT1A

associated with the 17p12 duplication, whereas it is often asymmetric

and nonhomogeneous in CMTX, sometimes rendering difficult the

differential diagnosis with acquired inflammatory neuropathies.

The demyelinating recessive forms, termed CMT4, usually have early

onset and run a more severe course than the dominant types. Pure

motor CMT types are now classified as distal hereditary motor

neuronopathy.

The diagnostic approach to the identification of the CMT subtype is

complex and cannot be based on the clinical phenotype alone, as

different forms are often clinically indistinguishable. However,

there are features that may be of help in addressing molecular

investigation in a single patient.

Late onset, prominent or peculiar sensory manifestations, autonomic

nervous system dysfunction, cranial nerve involvement, upper limb

predominance, subclinical central nervous system abnormalities,

severe scoliosis, early-onset glaucoma, neutropenia are findings

helpful for diagnosis.