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Charcot-marie-tooth Disease Type 4c

Disease Details

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Description: Charcot-Marie-Tooth disease type 4C is a genetic disorder characterized by progressive weakness and atrophy of muscles in the feet, legs, and hands, often accompanied by sensory loss.
Type: Charcot-Marie-Tooth disease type 4C (CMT4C) is an autosomal recessive disorder. This means both copies of the gene in each cell have mutations, and typically, each parent of an individual with an autosomal recessive condition carries one copy of the mutated gene but usually does not show signs and symptoms of the condition.
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 4C (CMT4C) typically presents in childhood, with symptoms often beginning between the ages of 2 and 10.
Prevalence: Charcot-Marie-Tooth disease type 4C (CMT4C) is a rare subtype of the disease. The exact prevalence of CMT4C is not well-documented, but CMT as a whole affects approximately 1 in 2,500 people. CMT4C is characterized by early onset of symptoms, usually in childhood, and involves progressive muscle weakness and sensory loss, particularly in the legs and arms.
Epidemiology: Charcot-Marie-Tooth disease type 4C (CMT4C) is a form of Charcot-Marie-Tooth disease, a group of inherited peripheral neuropathies. CMT4C is particularly rare and is characterized by early-onset, progressive muscle weakness and atrophy, primarily affecting the distal limbs, along with spinal deformities such as scoliosis. It is inherited in an autosomal recessive pattern and is caused by mutations in the SH3TC2 gene. Given its rarity, precise epidemiological data are limited. However, CMT4C is more frequently observed in populations with high rates of consanguinity.
Intractability: Charcot-Marie-Tooth disease type 4C (CMT4C) is generally considered intractable as there is currently no cure. Treatment options primarily focus on managing symptoms and improving quality of life, often through physical therapy, occupational therapy, orthopedic devices, and sometimes surgical interventions to correct deformities.
Disease Severity: Charcot-Marie-Tooth disease type 4C (CMT4C) can vary in severity. Most individuals experience moderate to severe symptoms, including progressive muscle weakness and atrophy, particularly in the distal limbs. Symptoms typically present in childhood or adolescence and can lead to significant impairment in mobility and function. The severity can vary even among affected family members.
Healthcare Professionals: Disease Ontology ID - DOID:0110183
Pathophysiology: Charcot-Marie-Tooth disease type 4C (CMT4C) is a subtype of Charcot-Marie-Tooth disease, which is a group of inherited peripheral neuropathies. The pathophysiology of CMT4C involves mutations in the SH3TC2 gene, located on chromosome 5q32. This gene is responsible for encoding a protein involved in the structure and function of myelin in peripheral nerves. Myelin is the insulating layer that surrounds nerves and is crucial for rapid and efficient transmission of electrical signals.

The mutations in SH3TC2 disrupt normal myelin function, leading to demyelination (loss of the myelin sheath) and subsequent axonal degeneration. This results in the clinical manifestations of CMT4C, which include muscle weakness and wasting, primarily in the distal limbs, sensory loss, and foot deformities such as high arches or hammertoes. The disease typically presents in childhood or adolescence and progressively worsens over time.
Carrier Status: Carrier status for Charcot-Marie-Tooth disease type 4C (CMT4C) can occur because it is an autosomal recessive disorder. This means that carriers have one mutated copy and one normal copy of the gene responsible for CMT4C, but they do not typically show symptoms. If both parents are carriers, there is a 25% chance with each pregnancy that their child will have CMT4C.
Mechanism: Charcot-Marie-Tooth disease type 4C (CMT4C) is a form of inherited peripheral neuropathy.

**Mechanism:**
CMT4C is caused by mutations in the SH3TC2 gene. This gene provides instructions for producing a protein that is crucial for the proper functioning of Schwann cells, which are essential for myelination in the peripheral nervous system. Myelination involves the formation of the myelin sheath, a protective covering that enables efficient transmission of nerve impulses.

**Molecular Mechanisms:**
Mutations in the SH3TC2 gene lead to the production of an abnormal protein or reduce the amount of functional protein, thereby impairing the function of Schwann cells. This deficiency negatively affects the myelination process, resulting in demyelination and subsequent axonal degeneration. The disrupted nerve signaling leads to the muscle weakness and sensory loss characteristic of CMT4C.

Understanding these mechanisms helps in exploring potential therapeutic approaches and provides insight into the broader category of inherited peripheral neuropathies.
Treatment: Charcot-Marie-Tooth Disease Type 4C (CMT4C) is a subtype of CMT characterized by genetic mutations leading to peripheral nerve damage. There is currently no cure for CMT4C, but treatment focuses on managing symptoms and improving quality of life.

1. **Physical Therapy**: To maintain muscle strength and flexibility, and to prevent muscle atrophy.
2. **Orthopedic Devices**: Braces or orthotic devices can help with mobility and support.
3. **Pain Management**: Over-the-counter pain relievers or prescription medications may be used for neuropathic pain.
4. **Surgical Interventions**: In some cases, surgery may be required to correct foot deformities.
5. **Occupational Therapy**: Helps individuals perform daily activities and maintain independence.
6. **Assistive Devices**: Canes, walkers, or wheelchairs may be necessary for mobility as the disease progresses.

Regular follow-up with a neurologist and a multidisciplinary healthcare team is essential for ongoing care and to address any complications.
Compassionate Use Treatment: Charcot-Marie-Tooth disease type 4C (CMT4C) is a subtype of Charcot-Marie-Tooth disease, a group of inherited neuropathies. CMT4C specifically is caused by mutations in the SH3TC2 gene and typically presents with severe demyelinating neuropathy.

1. **Compassionate Use Treatment**:
- Compassionate use treatments for CMT4C are generally provided on a case-by-case basis and may involve experimental therapies not yet approved by regulatory agencies. These treatments are granted to patients with serious or life-threatening conditions for whom no comparable or satisfactory alternative therapy options are available.

2. **Off-label Treatments**:
- Currently, there are no widely recognized off-label pharmaceutical treatments specifically for CMT4C. However, off-label use of medications may be considered to manage symptoms, such as:
- Gabapentin or pregabalin for neuropathic pain.
- Physical therapy to improve mobility and muscle strength.
- Orthopedic interventions to correct foot deformities or maintain walking ability.

3. **Experimental Treatments**:
- Gene therapy is a highly experimental approach being explored for various genetic disorders, including CMT4C. Efforts focus on correcting the underlying genetic defect.
- Clinical trials may be conducted to test novel drug candidates, but as of now, significant breakthroughs specifically targeting CMT4C have not yet been established.

Patients and caregivers should consult with specialized healthcare professionals to explore the most current and applicable treatment options, including participation in clinical trials if available.
Lifestyle Recommendations: Charcot-Marie-Tooth Disease Type 4C (CMT4C) is a genetic neurological disorder affecting the peripheral nerves. Here are some lifestyle recommendations for individuals with CMT4C:

1. **Physical Therapy**: Engage in regular physical therapy to help maintain muscle strength, flexibility, and mobility. Customized exercise programs can also prevent muscle atrophy and contractures.

2. **Occupational Therapy**: Work with an occupational therapist to learn techniques and use adaptive devices that help with daily activities, enhancing independence and quality of life.

3. **Low-Impact Exercises**: Participate in low-impact activities such as swimming, cycling, and walking. These exercises can help maintain cardiovascular health and muscle tone without putting too much strain on the joints.

4. **Proper Footwear**: Choose well-fitting, supportive shoes. Orthotic devices may also be recommended to correct foot deformities and improve walking stability.

5. **Assistive Devices**: Use braces, canes, walkers, or wheelchairs as needed to assist with mobility and prevent falls. Consulting a healthcare provider can determine the appropriate device.

6. **Nutrition**: Maintain a balanced diet to support overall health. Adequate nutrition can help manage weight, which is crucial for reducing stress on weakened muscles and joints.

7. **Avoid Overexertion**: Balance activity with rest to avoid fatigue and overexertion, which can exacerbate symptoms.

8. **Regular Medical Check-ups**: Keep up with regular visits to healthcare providers, including neurologists and genetic counselors, to monitor disease progression and manage symptoms effectively.

9. **Emotional Support**: Seek support from mental health professionals, support groups, or community resources to help cope with the emotional and psychological challenges of living with a chronic condition.

10. **Education**: Stay informed about the disease and current research developments. Knowledge can empower you to make better decisions about your health and treatment options.

These recommendations aim to help manage the symptoms and improve the quality of life for those with CMT4C. Always consult with healthcare providers for personalized advice and treatment plans.
Medication: Charcot-Marie-Tooth disease type 4C (CMT4C) is a subtype of Charcot-Marie-Tooth disease that involves degeneration of peripheral nerves, leading to muscle weakness and sensory loss. Currently, there are no specific medications to cure or halt the progression of CMT4C. Management generally focuses on symptomatic treatment and supportive care, including physical therapy, occupational therapy, orthopedic interventions, and sometimes medications to manage pain. Genetic counseling may also be beneficial for affected individuals and their families.
Repurposable Drugs: Charcot-Marie-Tooth disease type 4C (CMT4C) is a hereditary neuropathy caused by mutations in the SH3TC2 gene. Currently, there are no specific drugs approved to treat CMT4C, but certain repurposable drugs may provide symptomatic relief or slow disease progression in related neuropathies. Some repurposable drugs under investigation include:

1. **Ascorbic Acid (Vitamin C)**: Potentially beneficial due to its role in myelin maintenance and antioxidant properties.
2. **Pioglitazone**: A PPARγ agonist that may offer neuroprotective effects.
3. **N-Acetylcysteine (NAC)**: Known for its antioxidant properties, possibly reducing oxidative stress in neurons.

Further clinical trials are needed to confirm the efficacy of these drugs specifically for CMT4C. Always consult with a healthcare provider for personalized medical advice.
Metabolites: Charcot-Marie-Tooth disease type 4C (CMT4C) is a subtype of Charcot-Marie-Tooth disease, which is a group of inherited peripheral neuropathies. CMT4C specifically is associated with mutations in the SH3TC2 gene. Regarding metabolites, there is no detailed list of specific metabolites uniquely altered in CMT4C that is widely recognized or systematically reported. As a result, it is important to approach this disease primarily through genetic and clinical examination rather than focusing on metabolites.
Nutraceuticals: Currently, there is no established evidence to support the use of nutraceuticals specifically for Charcot-Marie-Tooth disease type 4C. Management typically focuses on supportive care, physical therapy, and orthopedic interventions. Consultation with a healthcare provider is recommended for personalized advice.
Peptides: Charcot-Marie-Tooth disease type 4C (CMT4C) is a recessive inherited neuropathy caused by mutations in the SH3TC2 gene. It is not directly associated with peptides or nanoparticles (nan). Research in the treatment of CMT4C may involve various molecular approaches, but specific interventions involving peptides and nanoparticles are not a primary focus as of the latest information. Management typically includes physical therapy, orthopedic devices, and symptomatic treatment.