Introduction:
Charcot-Marie-Tooth disease (CMT) is a nerve disorder subclinically categorized into numerous variants that are caused due to damage to the peripheral nerves. The peripheral nerve function is primarily affected. These nerves are responsible for transmitting information and signals from the brain and spinal cord to our body and the relay of sensory information back to the spinal cord and brain. It is named after three physicians who first described it in 1886 - Jean-Martin Charcot and Pierre Marie of France and Howard Henry Tooth of the United Kingdom.
What Is the Etiology Of Charcot- Marie -Tooth Disease?
Progressive muscle weakness is a characteristic change in adolescence or early adulthood, but disease onset can occur in any age group or decade. In CMT, the nerves that control the muscles can also be affected. Due to the longer distributed nerves being affected first, the clinical symptoms begin in the feet and lower legs and can progressively impact the fingers, hands, and arms. Most individuals with CMT also suffer physical disability wherein the psychosocial functions are considerably slowed down.
This disease is deemed as a common neurological disorder by inheritance, affecting 126,000 individuals in the United States and 2.6 million people worldwide. It is possible to have two or more types of CMT, which happens when the individual suffers mutations in two or more genes. This also gives it the characteristic of being a heterogeneous genetic disease. In heterogeneous genetic diseases, the mutations in different genes can produce similar clinical symptoms.
Particularly, the main theory accepted is the hypothesis that gene mutations in the genes that support or produce proteins involved in the structure and functioning of the peripheral nerve axon or the myelin sheath. According to traditional research, more than 40 genes have been identified in CMT, with each gene linked to multiple variants or gene types of the disease. Evidence also exists to show that cases of CMT are caused by the duplication of the PMP22 gene on chromosome 17. Due to the peripheral nerve malfunction, the gene defects in myelin cause dysfunction of the coating or the sheath that distorts or blocks nerve signals. The axon functions are limited in other alternate mutations of this disease, and axonal loss may occur.
How Is CMT Classified?
Based on the pathophysiology, they are classified into:
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CMT1 is caused by myelin sheath abnormalities. This is an autosomal dominant disorder.
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CMT2 results from axon abnormalities within the peripheral nerve cell and is less common than CMT1.
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CMT3 is a severe neuropathy caused by demyelinated neurons that begins in infants. These infants have a characteristic delay in motor skills development, sensory interruption, muscle weakness, and muscle atrophy.
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CMT4 is caused by a combination of demyelination of neurons and axonal or motor neuropathies. These are inherited by autosomally recessive traits.
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CMTX1 (also called CMT X, type 1) is an X chromosome-linked disease caused by mutations in the gene responsible for producing protein connexin-32. The function of connexin-32 protein is found in myelinating Schwann cells (cells that wrap around nerve axons and make up the myelin sheath) which are severely affected.
What Are the Clinical Symptoms of CMT?
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The earliest features of the disease may onset with the weakness or paralysis of the foot and lower leg muscles. The individual can hence have difficulty even lifting their foot, and because of the high gait during stepping or walking, it makes them prone to tripping or falling without support.
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Due to muscle loss and strain, the lower legs can be distinguished by an "inverted champagne bottle" shape. As the disease progresses, weakness may be felt in the hands with increased intolerance or a reduced ability to feel heat, cold, and touch due to sensory nerve degeneration. The proprioception is commonly affected as well in these individuals.
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Nerve pain in the feet may cause these patients to rely upon orthopedic devices to maintain mobility (depending on mild, moderate, or severe foot pain).
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Though the clinical symptoms and progression of the disease can vary from individual to individual, some common features can be observed like involuntary parafunctional habits like nighttime tooth grinding, jaw clenching (leading to regressive tooth alterations), vision squint, loss of height, hunch back appearance, malformed hips, etc.
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Tremors, visual difficulties, breathing impairment are indicative of nerve degeneration. Hence, hearing, vision, neck, shoulder, and diaphragm muscle issues are possible in these patients.
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Gastrointestinal problems can also be complicated in CMT, indirectly causing oral discomfort or difficulty swallowing (dysphagia).
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Muscle weakness, cramping, contractures, discomfort, or fatigue may be observed.
How to Diagnose CMT?
The physician may recommend electromyography and nerve conduction studies, which is the diagnostic gold standard for confirming CMT diagnosis.
EMG involves the needle electrode inserted through the skin to the muscle to measure the impacted muscle's bioelectrical activity. Specific abnormalities in these muscle activity readings imply axon loss. The advantage of EMG is that the neurologist can accurately assess the severity of peripheral nerve involvement.
Genetic testing can also be done by analyzing the individuals' blood samples for CMT detection. The neurologist may advise a nerve biopsy for confirmation by microscopically analyzing a small piece of peripheral nerve.
What Is the Treatment for CMT?
Though there is ideally no cure for this genetic disease, physical and occupational therapy along with orthopedic surgery and orthopedic device usage would be ideal for preventing long-term repercussions impacting the stamina and physical ability of the patient.
As advocated by the physician, physical therapy is pivotal for maintaining the long-term general systemic health of patients affected by CMT. It includes muscular strength training, stamina building or endurance providing exercise regimen, stretching exercises for muscles and ligaments, etc.
Ankle braces, orthopedic devices, ankle sprain prevention shoes, boots, thumb splints, etc., are other accessories for anti injury and mobility, providing physical protection to the wearer. The physician or neurologist may accordingly advise these devices to prevent physical disability from setting in.
Orthopedic surgery can also be advised based on the extent of pain and the ability of the patient to walk. Joint deformities and deformities of the hands and feet can also be treated successfully by currently advanced orthopedic surgical procedures.
Conclusion:
CMT does not usually pose a threat to life. The other name of CMT is hereditary motor and sensory neuropathy or peroneal muscular atrophy. The severity of symptoms of CMT can differ with each person. Most of the symptoms can be managed well with medication, assistive devices, and physical therapy. The earliest detection of CMT by the physician and neurologist is crucial for the management of the disorder to prevent and overcome long-term physical disability, progressive muscle weakness, and psychosocial limitations. One needs to take good care of their muscles and joints so as to reduce the risk of injury and loss of function.
