Charcot Marie tooth disease has been classified into various types depending upon the genes affected and the type of neuropathy caused by it. Charcot Marie Tooth disease Type 2 is a different type of neuropathy when compared to other CMT disease types because the pathological mechanism responsible for it is different. Charcot Marie Tooth disease is also known as hereditary sensorimotor neuropathy because it can involve both sensory and motor nerves of the peripheral nervous system.
What Is Charcot Marie Tooth Disease Type 2?
Charcot Marie Tooth disease type 2 is a type of sensorimotor neuropathy in which the mechanism of nerve damage the neuronal degeneration. It occurs due to mutation seen in ATP1A1 gene. It involves the damage to the axons of neural cells which causes the neuropathic symptoms. It is distinct from other types of Charcot Marie Tooth diseases because it is not associated with demyelination of nerve fibers as seen in have types.[1] The pattern of inheritance is autosomal dominant type but a few of its subtypes have been detected lately with the autosomal recessive type of inheritance.
The degeneration mechanism of neuronal axons is usually by Wallerian degeneration. It is an active process of degeneration in which the axons are damaged in a retrograde manner towards the cell body.[2] After axonal damage, there can be demyelination due to loss of Schwann cells and clearing of debris with the help of macrophages. It is a slowly progressing sensorimotor neuropathy which can progress till the 6th decade and sometimes the symptoms do not get much severe till later stages of the disease.
It is a peripheral neuropathy affecting the distal-most parts of the nerve fibers. The distinct feature is that it can affect both myelinated and unmyelinated nerve fibers. The appearance of the symptom is generally seen in the first two decades of life. It is characterized by slowly progressive muscle weakness found firstly in distal-most parts of the lower limbs and then involves upper limbs also. Muscle wasting and atrophy could also be seen in it. Difficulty in walking and other activities is the first symptom encountered by the patients. Due to the involvement of the lateral compartment of the lower limb, it can also present as foot drop.
On physical examination muscle wasting, bony deformities due to persistent muscle spasm, etc. can be seen. Deep tendon reflexes are severely diminished or even absent. Trophic ulcers, skin breakdown, burn due to non-sensation, non-healing lesions, etc. can be found on the skin.
Hand weakness occurs when the muscles of the upper limb are involved and there is difficulty in hand movements, finger control, handwriting, etc. suffered by the patient. Muscle cramps and pain are sometimes associated with it. Sensory loss of the associated skin and other tissues with pins and needle sensation, tingling, etc. is seen in early stages. Usually, the pain and temperature nerve fibers lack myelination and are spared in this disease but it can be involved sometimes in Charcot Marie Tooth disease type 2 because the mechanism is axonal degeneration and not the demyelination.
Conclusion
Charcot Marie Tooth disease type 2 is a sensory and motor neuropathy inherited from the parents most commonly as an autosomal dominant pattern. It is usually associated with Wallerianfamily history of similar neuropathies in the parents and other previous generations. Even a single parent if affected is sufficient to transmit the mutation in the next generation. A few other subtypes have been found in recent researches which are autosomal recessive in nature.
Progressive muscle weakness and loss of various cutaneous and deeper sensations with a slow progression is a characteristic feature of the Charcot a tooth disease. The usual age of presentation is 1st and 2nd decade of life. The involvement of both systems helps it to differentiate from other types of peripheral neuropathies. Consanguineous marriages should be avoided and prenatal detection of the mutation in the fetal DNA could be helpful in the prevention of the disease in future generations.
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