Charcot Marie Tooth (CMT) disease is the most common inherited neuromuscular disorder affecting approximately 1 person per 2500 populations in the United States. The disease is an inherited neuropathy with no known underlying metabolic disorder. It affects both sensory as well as motor nerves; autonomic nerves are usually not affected. The disease is also known as hereditary motor and sensory neuropathies. The disease is named after Jean-Martin Charcot, Pierre Marie and Howard Henry Tooth who first described the disease in 1886.
How Dangerous Is Charcot Marie Tooth & Is It Contagious?
Generally, Charcot Marie Tooth is a slow progressive neuropathy that leads to disability due to distal muscle weakness and deformities. The deterioration of motor function increases after the age of 50. Very rare cases of phrenic nerve involvement of the diaphragm are seen that can lead to ventilation problems. Generally, Charcot Marie Tooth is not related to increased mortality of shortening the life expectancy of patients.
Mostly, patients with Charcot Marie Tooth have a significant family history, but some cases may also be spontaneous mutations without any family history. Charcot Marie Tooth is usually seen in young age with people being in their first or second decade of life. Weakness and wasting is the most common complaint that may lead to difficulty walking, frequent tripping, frequent ankle sprains, falls, steppage and with worsening weakness, foot drop is noted. Foot deformities are also noted such as pes cavus (high heels) or hammertoe that can lead to calluses, ulcers, cellulitis, and lymphangitis. Weakness in the hands can cause poor finger control, poor handwriting, difficulty zipping and buttoning, and using small objects. Usually, no sensory complaints are there, but vibration and proprioception may be reduced and there may be a lack of sensory perception. The patient may also complain of muscle cramping, musculoskeletal and neuropathic pain. Some patients may complain of autonomic symptoms, however, they are rarely present.(1)
Since there is loss of protective sensations in the extremities, patients are at an increased danger of skin breakdown or burns, non-healing foot ulcers and in severe cases bilateral bony feet deformities as mentioned above. Patients are usually managed with orthoses to treat foot drop and bony foot deformities. Maternal Charcot Marie Tooth diseases can lead to increased risk of complications at the time of delivery, which can lead to increased emergency interventions at the time of birth.
Cause Of Charcot Marie Tooth Disease
Charcot Marie Tooth consists of a group of genetically different disorders that have similar clinical symptoms and more than 80 genes are implicated in the etiology of the disease. Charcot Marie Tooth can be subdivided into CMT 1, CMT 2, CMT 3, CMT 4, and Charcot Marie Tooth X and these divisions can be further subdivided. The disorder is associated with all forms of Mendelian inheritance pattern and can be autosomal dominant, autosomal recessive or X-linked dominant.
Autosomal dominant with band 17p11.2-12 is the most common form of inheritance that is seen in Charcot Marie Tooth 1A type of inheritance associated with hypertrophic neuropathy or with diffusely slow nerve conduction. Other CMT 1 (HMSN I) forms include Charcot Marie Tooth 1B (autosomal dominant), CMT 1C (unknown autosome), CMT X1 (X-linked dominant), CMT X2 (X-linked recessive), CMT X3 (X-linked recessive) and autosomal recessive Charcot Marie Tooth 1.
Charcot Marie Tooth 2 (HMSN II) has normal or borderline abnormal nerve conduction velocity and is either neuronal or axonal type. The subtypes include CMT 2A, CMT 2B, CMT 2C and CMT 2D, which are all autosomal dominant inheritance and autosomal recessive CMT 2 is also present.
Charcot Marie Tooth 3 (HMSN III) is also known as Dejerine-Sottas disease that is associated with hypertrophy of infancy and congenital hypomyelinated neuropathy. It is inherited in an autosomal recessive pattern. CMT 4 and CMT X are both demyelinating neuropathies.
HMSN IV is also known as Refsum syndrome and there is phytanic acid excess, which is inherited in an autosomal recessive pattern.
HMSN V is associated with spastic paraplegia; Roussy-Levy syndrome is inherited in dominant inheritance pattern. HMSN VI is associated with optic atrophy and HMSN VII is associated with retinitis pigmentosa.(1)