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Charcot-marie-tooth Disease Type 2e

Disease Details

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Description: Charcot-Marie-Tooth disease type 2E (CMT2E) is a genetic disorder characterized by progressive damage to the peripheral nerves, leading to muscle weakness and atrophy, primarily in the lower legs and feet.
Type: Charcot-Marie-Tooth disease type 2E (CMT2E) is a type of inherited neurological disorder. The genetic transmission for CMT2E is autosomal dominant.
Signs And Symptoms: Symptoms of CMT usually begin in early childhood or early adulthood but can begin later. Some people do not experience symptoms until their early 30s or 40s. Usually, the initial symptom is foot drop or high arches early in the course of the disease. This can be accompanied by hammertoe, where the toes are always curled. Wasting of muscle tissue of the lower parts of the legs may give rise to a "stork leg" or "inverted champagne bottle" appearance. Weakness in the hands and forearms occurs in many people as the disease progresses.Loss of touch sensation in the feet, ankles, and legs as well as in the hands, wrists, and arms occurs with various types of the disease. Early- and late-onset forms occur with 'on and off' painful spasmodic muscular contractions that can be disabling when the disease activates. High-arched feet (pes cavus) or flat-arched feet (pes planus) are classically associated with the disorder. Sensory and proprioceptive nerves in the hands and feet are often damaged, while unmyelinated pain nerves are left intact. Overuse of an affected hand or limb can activate symptoms including numbness, spasm, and painful cramping.Symptoms and progression of the disease can vary. Involuntary grinding of teeth and squinting are prevalent and often go unnoticed by the person affected. Breathing can be affected in some, as can hearing, vision, and neck and shoulder muscles. Scoliosis is common, causing hunching and loss of height. Hip sockets can be malformed. Gastrointestinal problems can be part of CMT, as can difficulty chewing, swallowing, and speaking (due to atrophy of vocal cords). A tremor can develop as muscles waste. Pregnancy has been known to exacerbate CMT, as well as severe emotional stress. Patients with CMT must avoid periods of prolonged immobility such as when recovering from a secondary injury, as prolonged periods of limited mobility can drastically accelerate symptoms of CMT.Pain due to postural changes, skeletal deformations, muscle fatigue, and cramping is fairly common in people with CMT. It can be mitigated or treated by physical therapies, surgeries, and corrective or assistive devices. Analgesic medications may also be needed if other therapies do not provide relief from pain. Neuropathic pain is often a symptom of CMT, though, like other symptoms of CMT, its presence and severity vary from case to case. For some people, pain can be significant to severe and interfere with daily life activities. However, pain is not experienced by all people with CMT. When neuropathic pain is present as a symptom of CMT, it is comparable to that seen in other peripheral neuropathies, as well as postherpetic neuralgia and complex regional pain syndrome, among other diseases.
Prognosis: The severity of symptoms varies widely even for the same type of CMT. Cases of monozygotic twins with varying levels of disease severity have been reported, showing that identical genotypes are associated with different levels of severity (see penetrance). Some patients are able to live a normal life and are almost or entirely asymptomatic. A 2007 review stated that, "life expectancy is not known to be altered in the majority of cases."
Onset: Charcot-Marie-Tooth disease type 2E (CMT2E) generally has an onset in childhood or adolescence. However, the exact age of onset can vary depending on the individual.
Prevalence: The prevalence of Charcot-Marie-Tooth disease type 2E (CMT2E) is not precisely known, but CMT overall affects about 1 in 2,500 people. CMT2E is one of the less common subtypes of Charcot-Marie-Tooth disease.
Epidemiology: Charcot-Marie-Tooth disease type 2E (CMT2E) is a subtype of Charcot-Marie-Tooth disease, a genetic disorder that affects the peripheral nerves. The epidemiology of CMT2E is as follows:

- **Prevalence**: CMT as a whole affects about 1 in 2,500 people globally. CMT2E is a rarer subtype, but precise prevalence data for CMT2E specifically are not well-documented due to its rarity.
- **Age of Onset**: Symptoms usually appear in the first or second decade of life but can vary.
- **Sex Distribution**: It affects both males and females equally.
- **Geographic Distribution**: CMT2E has been reported worldwide, with no specific geographic predilection.

The detailed epidemiological data specific to CMT2E may not be extensively documented due to its rarity and underreporting.
Intractability: Charcot-Marie-Tooth Disease Type 2E (CMT2E) is generally considered intractable, meaning it cannot be cured. Current treatments focus on managing symptoms and improving quality of life rather than halting or reversing disease progression. This can include physical therapy, occupational therapy, orthopedic devices, and, in some cases, medications to manage pain and other symptoms. Research is ongoing to find more effective treatments and potential cures.
Disease Severity: Charcot-Marie-Tooth disease type 2E (CMT2E) is a genetic disorder that primarily affects the peripheral nerves. The severity of CMT2E can vary widely among individuals. Some may experience mild symptoms, such as muscle weakness and sensory loss in the extremities, while others may have more severe manifestations, including significant mobility issues and muscle atrophy. The course of the disease is generally progressive, and symptoms often worsen over time. However, specific severity and progression can differ significantly based on the individual.
Healthcare Professionals: Disease Ontology ID - DOID:0110165
Pathophysiology: Charcot-Marie-Tooth disease type 2E (CMT2E) is a subtype of Charcot-Marie-Tooth disease, which is a group of inherited peripheral neuropathies. CMT2E specifically pertains to a type of axonal neuropathy. The pathophysiology involves mutations in the NEFL gene, which encodes the neurofilament light chain protein. This protein is a critical component of the neuronal cytoskeleton, and mutations can lead to abnormalities in axonal integrity and transport, resulting in the degeneration of peripheral nerves. This degeneration impairs the transmission of motor and sensory signals, leading to the characteristic symptoms of muscle weakness and atrophy, predominantly in the distal limbs, as well as sensory loss.
Carrier Status: Charcot-Marie-Tooth disease type 2E (CMT2E) is an autosomal dominant disorder caused by mutations in the NEFL gene. Carrier status does not typically apply to autosomal dominant conditions, as only one mutated copy of the gene is necessary to express the disease. In this case, someone who has a mutation in NEFL will typically exhibit symptoms of CMT2E.
Mechanism: Charcot-Marie-Tooth disease type 2E (CMT2E) is a subtype of Charcot-Marie-Tooth disease, which is a group of inherited disorders affecting the peripheral nerves.

**Mechanism:**
CMT2E is characterized by the degeneration of axons, the long projections of nerve cells that transmit electrical impulses to muscles and sensory organs. This leads to muscle weakness and atrophy, particularly in the distal muscles of the extremities (the lower legs, feet, hands, and forearms). Sensory deficits can also occur.

**Molecular Mechanisms:**
CMT2E is commonly associated with mutations in the NEFL gene, which encodes the neurofilament light chain (NFL) protein. NFL is a crucial component of the intermediate filaments in neurons, providing structural support and facilitating axonal transport. Mutations in NEFL disrupt the assembly and function of neurofilaments, leading to impaired axonal transport and structural integrity. This disruption contributes to axonal degeneration and the ensuing neurological symptoms of CMT2E.

Understanding these molecular mechanisms aids in developing therapeutic targets aimed at modulating neurofilament function and stabilizing axonal structures.
Treatment: Charcot-Marie-Tooth Disease Type 2E (CMT2E) primarily involves supportive treatments aimed at managing symptoms and improving quality of life. These treatments may include:

1. **Physical Therapy**: Exercises to maintain muscle strength, flexibility, and mobility.
2. **Orthotic Devices**: Braces or custom-made shoes to aid in walking and prevent injury.
3. **Occupational Therapy**: Assistance with daily activities and usage of adaptive devices.
4. **Pain Management**: Medications to control neuropathic pain.
5. **Surgical Interventions**: In some cases, surgery may be necessary to correct foot deformities or other skeletal abnormalities.

Currently, there is no cure for CMT2E, and treatments focus on symptom management and supportive care.
Compassionate Use Treatment: Charcot-Marie-Tooth disease type 2E (CMT2E) is a subtype of CMT caused by mutations in the NEFL gene. For compassionate use treatment, off-label, or experimental treatments currently being explored include:

1. **Gene Therapy**: Research is ongoing to develop therapies that target the NEFL gene to correct or mitigate the defective gene's effects.

2. **Nerve Growth Factors**: Experimental treatments using neurotrophic factors like CNTF (ciliary neurotrophic factor) are being studied to support nerve health and function.

3. **Antisense Oligonucleotides (ASOs)**: These are designed to specifically target and reduce expression of the mutated NEFL gene, and are being explored in preclinical models.

4. **Stem Cell Therapy**: Investigations are underway to determine the viability of stem cell transplantation to repair or replace damaged nerve tissues.

5. **Pharmaceutical Agents**: Certain drugs that modulate cellular stress responses, such as p38 MAP kinase inhibitors or HDAC inhibitors, may offer neuroprotective benefits and are under research for off-label use.

These treatments are typically in experimental stages or available through clinical trials and compassionate use programs, and they should be pursued under the guidance of a specialist experienced in managing CMT2E.
Lifestyle Recommendations: Lifestyle Recommendations for Charcot-Marie-Tooth Disease Type 2E (CMT2E):

1. **Physical Therapy**: Engage in regular physical therapy to maintain muscle strength and prevent atrophy. Tailored exercises can help improve mobility and balance.

2. **Occupational Therapy**: Work with an occupational therapist to adapt daily activities and use assistive devices that enhance independence.

3. **Orthopedic Support**: Use braces, orthotic devices, or special footwear to support weakened limbs and improve walking stability.

4. **Low-Impact Exercise**: Participate in low-impact exercises like swimming, cycling, and yoga to maintain cardiovascular health without putting excess strain on muscles.

5. **Healthy Diet**: Follow a balanced diet rich in vitamins and minerals to support overall health and potentially slow disease progression.

6. **Avoid Overexertion**: Balance activity with rest to avoid muscle fatigue and injury.

7. **Routine Medical Care**: Regular check-ups with a neurologist and other specialists to monitor disease progression and manage symptoms effectively.

8. **Pain Management**: Use prescribed pain management strategies, including medication, hot/cold therapy, and relaxation techniques.

9. **Foot Care**: Maintain proper foot hygiene and care to prevent sores and infections, which can be common in individuals with reduced sensation.

10. **Safety Modifications at Home**: Make home modifications like installing grab bars, using non-slip mats, and ensuring good lighting to prevent falls and injuries.
Medication: Charcot-Marie-Tooth disease type 2E (CMT2E) is a subtype of Charcot-Marie-Tooth disease characterized by progressive muscle weakness and atrophy. Currently, there is no cure, and management primarily focuses on symptomatic relief and supportive care. Physical therapy, occupational therapy, orthotic devices, and sometimes surgical interventions are commonly used to help maintain mobility and function. Medications may be prescribed for pain management or other symptoms, but specific pharmacological treatments targeting the underlying cause of CMT2E are not available yet.
Repurposable Drugs: As of now, there are no widely recognized repurposable drugs specifically for Charcot-Marie-Tooth disease type 2E (CMT2E). Research is ongoing to identify potential therapies. CMT2E is a genetic disorder primarily managed through supportive care, including physical therapy, occupational therapy, and orthopedic devices to improve mobility and quality of life. Always consult a healthcare provider for the most current treatment options.
Metabolites: Charcot-Marie-Tooth disease type 2E (CMT2E) primarily affects peripheral nerves and is linked to mutations in the NEFL gene, which codes for the neurofilament light chain. The metabolism of individuals with CMT2E involves typical cellular metabolites; however, specific abnormalities in these metabolites related to CMT2E are not well-documented. Therefore, there are no unique, disease-specific metabolites widely recognized for diagnostic or monitoring purposes in CMT2E. Research is ongoing to better understand the metabolic changes associated with this condition.
Nutraceuticals: Charcot-Marie-Tooth Disease Type 2E (CMT2E) is a genetic disorder affecting the peripheral nerves. The term "nan" might be unclear, but if it refers to "not available" or "not applicable," it would indicate that specific nutraceutical treatments for CMT2E are either not well-documented or studied. Generally, management includes physical therapy, occupational therapy, and possibly orthotic devices. Nutritional supplements might not have a direct impact on the disease itself but could support overall health. For specific recommendations, consult a healthcare professional.
Peptides: Charcot-Marie-Tooth Disease Type 2E (CMT2E) is a subtype of Charcot-Marie-Tooth disease, a hereditary neuropathy. CMT2E is associated with mutations in the NEFL gene, which encodes the neurofilament light chain protein. These mutations affect the axons, leading to progressive muscle weakness and atrophy.

Research into the use of peptides and nanotechnology for the treatment or management of CMT2E is ongoing. Peptides might be designed to interact with problematic proteins or pathways specific to this disease subtype. Nanotechnology could potentially be employed for targeted drug delivery, enhancing the efficacy and reducing side effects of treatments. However, there are no widely accepted peptide or nanotechnology-based treatments for CMT2E as of now, and such options remain largely experimental.