Charcot-Marie-Tooth disease (CMT) is a slowly progressive sensorimotor neuropathy that manifests as muscular atrophy and weakness of the lower extremities. There are two forms of this disease based on electrophysiologic and pathologic findings. In type I disease, the pathologic abnormality is demyelination resulting in a marked reduction of motor nerve conduction velocities (generally < 42 m/sec) and an onion bulb appearance of the swollen portions of nerves on histopathologic examination. In type II disease, the pathology is of the neuron itself and not the myelin sheath, there are no onion bulb swellings of the nerves on histopathologic exam, and nerve conduction velocities are normal or nearly so.
CMT is an inherited disorder. Based on the form of inheritance and the genes affected there are several types of CMT. In the autosomal dominant inherited forms there are several types to include CMT1A (believed to be the most common type with the genetic abnormality located on chromosome 17), CMT1B (genetic abnormality on chromosome 1), CMT1C, CMT2A, CMT2B, and hereditary neuropathy with pressure palsies. CMT-2 usually presents later in life and usually lacks foot and back deformities, upper limb involvement, areflexia, and tremor. CMT1-AR is the autosomal recessive form of disease with CMTX being the X-linked form. Deferine-Sottas disease (severe neuropathy affecting young children) and Refsum’s disease are two other types of hypertrophic neuropathy.
Physical findings include high-arched feet, hammer toes, and kyphoscoliosis. Physical exam findings of thickened peripheral nerves, postural tremor, and absent or reduced reflexes are suggestive. Muscular atrophy of the lower extremities results in the characterisitic inverted champagne bottle abnormality. Family members should be screened although they may be unaware of their slowly progressive symptoms.
Molecular genetic testing may help identify underlying disease. Peripheral nerve myelin protein 22 (PMP22) gene duplication on chromosome 17 is the most common cause of CMT disease type 1. P0 gene mutation is responsible for another cause of type 1 disease. Connexin 32 mutation is seen with X linked CMT disease.