Charcot Marie Tooth Disease Research Paper

Signs and symptoms

Charcot Marie Tooth disease encompasses a group of inherited disorders that affect motor and sensory peripheral nerves. It is a type of neuropathy characterized by damage to myelin sheaths and nerve axon structure that results in impaired ability of the peripheral nervous system to send signals or relay sensory information. CMT typically presents with distal predominance of limb-muscle wasting, weakness, and sensory loss , . Symptoms start in the feet, which commonly have high arches, hammer toes, intrinsic muscle weakness, and wasting. The disease then begins to affect the legs and the lower thighs, which results in distal atrophy of the lower limbs. The hands become affected, followed by the forearms. Sensory loss also

occurs and patients experience decreased sensation of vibration, touch and pain in the feet and hands in particular. Deep-tendon reflexes are reduced, and skeletal deformities, often involving the feet, are common.

Onset and progression
Disease onset usually occurs before the patient reaches their 20s and progresses over time. Upon disease onset patients may notice difficulty walking or running, twisting of the ankle, tripping, weakness, sensory loss of distal segments of lower limbs, and reduced deep-tendon reflexes. Other common early symptoms are hand tremors, muscle cramps, cold feet, foot callosities, and acrocyanosis. Onset can sometimes occur so early that it causes hypotonia (floppy baby syndrome), delayed motor development, and toe walking, while for other CMT subtypes onset can occur late in life , .

Common CMT subtypes and their associated phenotypes
CMT1 (dominant, demyelinating): Extensive slowing of motor and sensory nerve conduction velocity as well as variable degree of progression and disability . Nerve biopsies show myelin abnormalities as well as secondary axonal degeneration , .
CMT2 (dominant or recessive, axonal): Nerve conduction velocity slightly decreased. Nerve biopsies indicate chronic axonal neuropathy and, in certain cases, patients experience hearing and vision impairment.
CMTX (X-linked dominant or recessive): Since this trait is x-linked, men more affected than women. Motor nerve conduction velocity is intermediate in men, and around CMT2 ranges in women. CMTX, uniquely, can present with asymmetrical conduction velocity slowing as well as deafness and intellectual disabilities. It is associated with axonal loss, and some demyelination.
Intermediate CMT: This subtype is mild to moderate severity, with conduction velocities somewhere between those found in CMT1 and CMT2 patients. Intermediate CMT also presents with pathological features of both CMT1 and CMT2 subtypes.
CMT3: This subtype is known for early onset and is more severe than CMT1. Neuron conduction velocities are very slow and nerve biopsies show dysmyelination as well as onion bulbs .
dHMN: Preserved or mildly slowed nerve conduction velocities, variable onset, and occasionally vocal cord palsy causing respiratory difficulties.
CMT4 (recessive, demyelinating): It has more severe course than CMT1 and earlier onset. Along with slowed conduction velocities it is associated with impaired vocal cord movement, hearing loss, and facial and diaphragmatic weakness.
CMT5: Associated with involvement of pyramidal neurons, which affects deep-tendon reflexes and can result in spastic paraplegia. This subtype usually presents with axonal loss and reduced amplitudes of sensory action potentials .
CMT6: Is characterized by early onset and optic atrophy that results in severe visual loss .