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Charcot-Marie-Tooth Disease (CMT)


What is Charcot-Marie-Tooth disease type 1 (CMT1)?

CMT type 1 is the most common subtype of CMT, accounting for roughly two-thirds of all cases. CMT1 is inherited in an autosomal dominant pattern.

What are the symptoms of CMT1?

CMT1 is characterized by muscle weakness and atrophy, which can lead to repeated ankle sprains, and changes in sensation (paresthesia), which can cause clumsiness. Symptoms of this form of CMT usually start in childhood and mostly affect the periphery of the body, particularly in the feet, lower part of the legs, hands, and forearms. Patients with CMT1A may have associated sleep apnea (stop breathing while sleeping).1,2

What causes CMT1?

CMT1 is caused by damage to the myelin sheath covering nerves. CMT1 is commonly referred to as “demyelinating” CMT.

A subtype of CMT1 called CMT1A (caused by a duplication or, less commonly, a point mutation in the PMP22 gene on chromosome 17) accounts for around 70% to 80% of CMT1 cases, making it the most common subtype of CMT1. Duplication of PMP22 leads to accumulation of the peripheral myelin protein 22 (PMP22) protein, and point mutations alter its distribution. Patients with point mutations usually have more prominent clinical manifestations. PMP22 is vital for the normal creation and maintenance of the myelin sheath. CMT1 patients usually present with typical CMT onset within adolescence but remain ambulatory with no reduced life expectancy.

CMT1B is the second most common subtype of CMT1. CMT1B is caused by a defect within the MPZ gene, which lies on chromosome 1. The MPZ gene produces myelin protein zero (MPZ protein), and the disruption of this mutated protein causes deficits within the myelin sheath. There are also mutations within the MPZ genetic region of DNA that alter the ability of cells to edit MPZ efficiently.3 CMT1B patients have onset and symptoms similar to those of CMT1A patients, although there is a wide range of variability within CMT1B.

Other rare forms of CMT1 and their gene defects include:

Diagnosis Associated Gene

Roussy-Levy syndrome is a CMT1 phenotype (physical characteristics) with manifestations that include postural tremor (involuntary shaking), difficulty walking, distal (far from the center of the body) muscle atrophy, foot deformities, absent deep-tendon reflexes, and mild distal sensory loss.


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