Peroneal Muscular Atrophy
Disease Details
Family Health Simplified
- Description
- Peroneal muscular atrophy, also known as Charcot-Marie-Tooth disease, is a hereditary neurological disorder characterized by progressive loss of muscle tissue and touch sensation, primarily affecting the feet and legs.
- Type
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Peroneal muscular atrophy, also known as Charcot-Marie-Tooth disease (CMT), is a type of hereditary motor and sensory neuropathy. It primarily involves progressive loss of muscle tissue and touch sensation across various parts of the body. The disease has several subtypes, each with different genetic causes and inheritance patterns. The most common forms are:
1. **CMT1**: Autosomal dominant
2. **CMT2**: Autosomal dominant
3. **CMTX**: X-linked
Less common types can be inherited in an autosomal recessive manner. - 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
- Peroneal muscular atrophy, also known as Charcot-Marie-Tooth (CMT) disease, typically has an onset in adolescence or early adulthood, although symptoms can sometimes appear in childhood or later in adulthood. The age of onset can vary depending on the specific type and genetic factors involved.
- Prevalence
- Peroneal muscular atrophy, also known as Charcot-Marie-Tooth disease, has an estimated prevalence of about 1 in 2,500 people worldwide.
- Epidemiology
- Peroneal muscular atrophy, also known as Charcot-Marie-Tooth disease (CMT), is one of the most common inherited neurological disorders. CMT affects approximately 1 in 2,500 people worldwide. The condition is caused by mutations in genes that affect the structure and function of peripheral nerves, leading to progressive muscle weakness and atrophy. The disease can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner, with the autosomal dominant type being the most prevalent. Symptoms typically begin in adolescence or early adulthood and progress slowly over time.
- Intractability
- Peroneal muscular atrophy, also known as Charcot-Marie-Tooth disease (CMT), is a genetic disorder that currently has no cure, making it intractable. However, the symptoms can be managed through physical therapy, occupational therapy, orthopedic devices, and sometimes surgery. Genetic counseling may also be helpful for affected families.
- Disease Severity
- Peroneal muscular atrophy, also known as Charcot-Marie-Tooth disease, is a group of inherited disorders that affect the peripheral nerves. Disease severity can vary widely among individuals, ranging from mild to severe. Symptoms may include muscle weakness, atrophy, and sensory loss primarily in the lower legs and feet, but can also affect the hands and arms. The progression of the disease is typically slowly progressive, and while it can lead to significant physical impairment, it is not usually life-threatening.
- Healthcare Professionals
- Disease Ontology ID - DOID:10595
- Pathophysiology
- Peroneal muscular atrophy, also known as Charcot-Marie-Tooth disease, primarily involves the degeneration of peripheral nerves, leading to muscle weakness and atrophy. The condition is often caused by genetic mutations that affect the production of proteins necessary for myelin (the protective sheath around nerves) or axonal function (nerve fibers). This disruption impairs nerve signal transmission, resulting in the progressive loss of function and muscle degeneration, particularly in the lower legs and feet, and sometimes in the hands and forearms.
- Carrier Status
- Peroneal muscular atrophy, also known as Charcot-Marie-Tooth disease, is a hereditary condition. Carrier status is relevant primarily in the context of autosomal recessive and X-linked forms of the disease. In autosomal recessive forms, an individual must inherit two copies of the mutated gene (one from each parent) to develop symptoms. Carriers, with just one copy of the mutation, typically do not show symptoms but can pass the mutated gene to their offspring. In X-linked forms, males with the mutation exhibit symptoms, while females with one mutated gene are usually carriers who may have mild to no symptoms.
- Mechanism
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Peroneal muscular atrophy, also known as Charcot-Marie-Tooth disease (CMT), encompasses a group of inherited disorders that affect the peripheral nerves. Here are the mechanisms and molecular mechanisms involved:
**Mechanism:**
1. **Demyelination or Axonal Degeneration:** CMT can result from defects causing demyelination (loss of the myelin sheath insulating the nerves) or axonal degeneration (loss of nerve fibers themselves).
2. **Peripheral Neuropathy:** This leads to progressive weakness and atrophy of the muscles, especially in the lower legs and feet, as well as sensory loss.
**Molecular Mechanisms:**
1. **Genetic Mutations:** CMT is caused by mutations in various genes that encode proteins essential for peripheral nerve function.
- **PMP22 Duplication:** One common mutation in CMT1A involves duplication of the PMP22 gene, which encodes a myelin protein.
- **MFN2 Mutations:** In CMT2A, mutations in the MFN2 gene, involved in mitochondrial fusion, can cause axonal degeneration.
2. **Protein Misfolding and Aggregation:** Mutations can result in misfolded proteins that aggregate and cause cellular stress.
3. **Defective Myelin Formation:** In demyelinating types of CMT, mutations disrupt the formation or maintenance of the myelin sheath.
4. **Impaired Axonal Transport:** Mutations affecting axonal transport proteins may result in defective nerve transmission.
These molecular defects disrupt the normal function of peripheral nerves, leading to the clinical manifestations of peroneal muscular atrophy. - Treatment
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Peroneal muscular atrophy, also known as Charcot-Marie-Tooth disease, is a hereditary neurological disorder that affects the peripheral nerves. Treatment focuses on managing symptoms and improving quality of life. It may include:
- Physical therapy to maintain muscle strength and flexibility.
- Orthotic devices like braces or splints to support weakened muscles and improve mobility.
- Pain management through medications or other therapies.
- Occupational therapy to aid in daily activities and hand function.
- In some cases, surgical interventions to correct bone deformities or improve limb function.
- Genetic counseling for affected individuals and families to understand the inheritance pattern and risks.
There is currently no cure for Charcot-Marie-Tooth disease, but ongoing research aims to find more effective treatments. - Compassionate Use Treatment
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Peroneal muscular atrophy, also known as Charcot-Marie-Tooth disease (CMT), involves progressive muscle wasting and loss of sensation. Currently, there isn't a cure for CMT, but several off-label and experimental treatments are being explored:
1. **Compassionate Use Treatments**:
- **Nusinersen (Spinraza)**: Originally approved for spinal muscular atrophy, some researchers are investigating its efficacy for CMT.
- **Gene Therapy**: Experimental approaches aiming to correct or mitigate the genetic defects causing CMT.
2. **Off-Label Treatments**:
- **High-Dose Ascorbic Acid (Vitamin C)**: Suggested to potentially slow disease progression in some forms of CMT.
- **Gabapentin and Pregabalin**: Anticonvulsants used off-label to manage neuropathic pain associated with CMT.
3. **Experimental Treatments**:
- **PXT3003**: A combination of three molecules (baclofen, naltrexone, and sorbitol) currently under clinical investigation for its potential to slow down CMT progression.
- **Stem Cell Therapy**: Early-stage research exploring the use of mesenchymal stem cells to promote nerve repair and regeneration.
It's important to consult with healthcare providers for personalized treatment recommendations and to discuss potential involvement in clinical trials. - Lifestyle Recommendations
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Peroneal muscular atrophy, also known as Charcot-Marie-Tooth disease, primarily affects the peripheral nerves and leads to muscle weakness and atrophy. Lifestyle recommendations to manage this condition include:
1. **Physical Therapy**: Engaging in regular physical therapy can help maintain muscle strength and mobility.
2. **Occupational Therapy**: This aids in performing daily activities independently through adaptive techniques and tools.
3. **Exercise**: Non-strenuous exercises like swimming or low-impact aerobics can improve muscle tone without overexerting weak muscles.
4. **Orthopedic Devices**: Using braces or orthotic devices can provide support and improve walking ability.
5. **Foot Care**: Regular foot care is crucial due to the risk of ulcers and infections resulting from reduced sensation.
6. **Healthy Diet**: Eating a balanced diet can support overall health and manage any associated weight issues.
7. **Avoid Alcohol and Smoking**: Both can exacerbate symptoms and lead to further nerve damage.
8. **Rest**: Ensuring sufficient rest to prevent overexertion and manage fatigue.
These lifestyle adjustments, in conjunction with medical care, can help improve quality of life and manage symptoms effectively. - Medication
- Peroneal muscular atrophy, also known as Charcot-Marie-Tooth disease, primarily focuses on managing symptoms and maintaining functionality. Medications might include pain relievers, such as nonsteroidal anti-inflammatory drugs (NSAIDs) for pain management, and neuropathic pain medications like gabapentin or pregabalin. Physical therapy, occupational therapy, and orthopedic devices are commonly used to support mobility and muscle strength.
- Repurposable Drugs
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Peroneal muscular atrophy, also known as Charcot-Marie-Tooth (CMT) disease, is a group of inherited disorders that affect the peripheral nerves. There is ongoing research into repurposing existing drugs to manage its symptoms or slow its progression. Some drugs under investigation include:
1. **Gabapentin**: Originally approved for epilepsy and neuropathic pain, it may help alleviate pain and discomfort in CMT patients.
2. **N-Acetylcysteine (NAC)**: An antioxidant that has potential to reduce oxidative stress in nerve cells.
3. **Ascorbic Acid (Vitamin C)**: Some studies suggest it might slow nerve damage in certain subtypes of CMT.
Always consult healthcare professionals for current and personalized advice. - Metabolites
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Peroneal muscular atrophy, also known as Charcot-Marie-Tooth disease, can involve abnormalities in various metabolites due to its impact on peripheral nerves and muscle metabolism. Specific metabolites may include:
1. **Lactic Acid**: Elevated levels can occur due to muscle weakness and inefficient energy usage.
2. **Creatine**: Muscle degradation might affect creatine metabolism.
3. **Alanine and other amino acids**: Irregularities in amino acid metabolism due to muscle atrophy.
Further investigations and patient-specific assessments are often necessary to precisely identify metabolite changes. - Nutraceuticals
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For **peroneal muscular atrophy** (also known as Charcot-Marie-Tooth disease or CMT), nutraceuticals are not part of the standard treatment regimen. While some patients explore supplements to support nerve health, there is limited scientific evidence to support their efficacy. Consulting a healthcare provider is recommended before starting any nutraceuticals.
Research involving nanotechnology for CMT is in its early stages. Nanomedicine may offer future therapeutic options, such as targeted drug delivery, but these applications are still largely experimental and not yet in clinical use. - Peptides
- Peroneal muscular atrophy, also known as Charcot-Marie-Tooth disease (CMT), is a hereditary disorder that affects the peripheral nerves. Specific peptides have not been established as a standard treatment or therapeutic approach for this condition. Research in nanotechnology may hold potential for future therapeutic developments, but there are no widely accepted nanotechnology-based treatments for CMT at this time. Most current treatments focus on managing symptoms and improving the quality of life through physical therapy, orthotic devices, and sometimes surgical interventions.