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Charcot-marie-tooth Disease Type 4h

Disease Details

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Description: Charcot-Marie-Tooth disease type 4H is a hereditary motor and sensory neuropathy characterized by progressive muscle weakness and atrophy, primarily affecting the feet, legs, hands, and arms, often accompanied by sensory loss and foot deformities due to mutations in the FGD4 gene.
Type: Charcot-Marie-Tooth disease type 4H is 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: Charcot-Marie-Tooth disease type 4H typically has an onset in early childhood.
Prevalence: Charcot-Marie-Tooth disease type 4H (CMT4H) is a rare variant of the Charcot-Marie-Tooth disease group. The exact prevalence is not well-documented due to its rarity, but Charcot-Marie-Tooth disease as a whole affects approximately 1 in 2,500 people.
Epidemiology: Charcot-Marie-Tooth (CMT) disease type 4H is a rare subtype of Charcot-Marie-Tooth disease, which is a group of inherited neuropathies. It falls under the category of autosomal recessive demyelinating forms of CMT. The exact prevalence of CMT type 4H is not well-documented, but CMT in general affects about 1 in 2,500 people globally. Type 4H is associated with mutations in the FGD4 gene (also known as FRABIN), and it is considered very rare within the broader spectrum of CMT disorders.
Intractability: Charcot-Marie-Tooth disease type 4H (CMT4H) is considered intractable because there is no cure currently available. The disease is a genetic disorder that affects the peripheral nerves, leading to progressive muscle weakness and atrophy. Treatment focuses on managing symptoms and improving quality of life through physical therapy, orthotic devices, and sometimes surgical interventions. Research is ongoing, but at present, the disease remains chronic and progressive.
Disease Severity: Charcot-Marie-Tooth disease type 4H (CMT4H) is a subtype of Charcot-Marie-Tooth disease, which is a group of inherited neuropathies. CMT4H is characterized by a range of severity from mild to severe. The onset is typically in childhood or adolescence, and symptoms may include muscle weakness and atrophy, sensory loss, and foot deformities. The progression of the disease can vary widely among individuals.
Healthcare Professionals: Disease Ontology ID - DOID:0110192
Pathophysiology: Charcot-Marie-Tooth disease type 4H (CMT4H) is a subtype of Charcot-Marie-Tooth disease, which is a group of inherited peripheral neuropathies. The pathophysiology of CMT4H involves mutations in the FGD4 gene, which encodes a protein called Frabin. This protein is involved in the organization of the actin cytoskeleton and is vital for Schwann cell function and myelin maintenance.

Mutations in FGD4 lead to disrupted signaling pathways affecting Schwann cell development and the myelination process. This causes the myelin sheaths around peripheral nerves to deteriorate, leading to the characteristic symptoms of distal muscle weakness, atrophy, and sensory loss. The disease typically follows an autosomal recessive inheritance pattern.
Carrier Status: Charcot-Marie-Tooth disease type 4H (CMT4H) is inherited in an autosomal recessive manner. This means that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the disease. Carriers, who have just one copy of the mutated gene, typically do not show symptoms of the disease but can pass the mutation to their offspring.
Mechanism: Charcot-Marie-Tooth disease type 4H (CMT4H) is a subtype of Charcot-Marie-Tooth disease, which is a group of inherited neuropathies. The mechanism and molecular mechanisms of CMT4H are as follows:

**Mechanism:**
CMT4H primarily affects the peripheral nerves, leading to progressive muscle weakness and atrophy. It is inherited in an autosomal recessive pattern.

**Molecular Mechanisms:**
CMT4H is caused by mutations in the FGD4 gene, also known as FRABIN. The FGD4 gene encodes a protein involved in actin cytoskeleton organization, cell shape modulation, and signal transduction pathways. Mutations in FGD4 disrupt its normal function, leading to impaired Schwann cell myelination. This affects the production and maintenance of the myelin sheath, which insulates nerve fibers and is critical for efficient nerve signal transmission. Consequently, peripheral nerve function is compromised, manifesting in the clinical symptoms of CMT4H.
Treatment: Charcot-Marie-Tooth disease type 4H (CMT4H) is a rare genetic disorder that affects the peripheral nerves. Treatment primarily aims to manage symptoms and improve quality of life, since there is no cure for CMT4H. Common approaches include:

1. **Physical Therapy:** Exercises to maintain muscle strength, flexibility, and range of motion.
2. **Occupational Therapy:** Techniques and tools to assist with daily activities and improve fine motor skills.
3. **Orthopedic Aids:** Braces, custom-made shoes, and other aids to support mobility and correct deformities.
4. **Pain Management:** Medications or other therapies to manage neuropathic pain.
5. **Surgical Interventions:** In some cases, surgery may be necessary to correct severe foot or spine deformities.
6. **Genetic Counseling:** To provide information and support for affected individuals and their families.
Compassionate Use Treatment: Charcot-Marie-Tooth Disease Type 4H (CMT4H) is a rare, hereditary neurological disorder characterized by progressive loss of muscle tissue and touch sensation across various parts of the body. For such rare conditions, treatment options may be limited and typically focus on managing symptoms and improving quality of life.

### Compassionate Use Treatment
Compassionate use, or expanded access, allows patients with serious or life-threatening conditions to access investigational drugs or treatments outside of clinical trials when no comparable or satisfactory alternative therapies are available. For CMT4H, compassionate use treatments might include:

1. **Gene Therapy**: Though experimental, gene therapy aims to correct the genetic mutations responsible for CMT4H.
2. **Nerve Growth Factors**: Investigational drugs may be used to promote nerve regeneration and repair.

### Off-label or Experimental Treatments
Treatments considered off-label or experimental for CMT4H might include:

1. **Vitamin and Supplementation**: High-dose vitamin C and other supplements have been explored for their potential to slow disease progression.
2. **Pediatric Trials**: Some investigational drugs may specifically target the genetic mutation associated with CMT4H and could be available through clinical trials.
3. **Stem Cell Therapy**: Experimental use of stem cells to regenerate damaged neural tissues.
4. **Pharmacological Agents**: Drugs like ascorbic acid (vitamin C) and others may be used off-label based on their potential neuroprotective effects.

Given the complexity and rarity of CMT4H, these treatments typically require close collaboration with a medical team specializing in genetic and neuromuscular disorders.
Lifestyle Recommendations: For Charcot-Marie-Tooth Disease Type 4H (CMT4H), lifestyle recommendations include:

1. **Physical Therapy:** Engaging in regular physical therapy can help maintain muscle strength and flexibility.
2. **Assistive Devices:** Using braces or orthotic devices can provide support and improve mobility.
3. **Low-Impact Exercise:** Activities such as swimming or cycling are beneficial without putting excess stress on the muscles and joints.
4. **Healthy Diet:** Maintaining a balanced diet to support overall health and manage weight, which can reduce strain on muscles and joints.
5. **Foot Care:** Proper foot care is essential to prevent injuries, ulcers, or infections due to reduced sensation.
6. **Avoiding Alcohol and Smoking:** Both can exacerbate neuropathy and overall health issues.
7. **Regular Medical Follow-up:** Ongoing consultation with healthcare providers to adjust treatment plans and monitor progression.
8. **Occupational Therapy:** To help with daily activities and adaptations in the home and workplace.
9. **Mental Health Support:** Psychological counseling or support groups can offer emotional support and coping strategies.

Implementing these lifestyle adjustments can help manage the symptoms and improve the quality of life for those with CMT4H.
Medication: Charcot-Marie-Tooth disease type 4H (CMT4H) currently has no specific medication to cure the disease. Treatment mainly focuses on managing symptoms and improving quality of life through physical therapy, occupational therapy, orthopedic devices, and sometimes surgical interventions. Pain management strategies might include analgesics, while medications for associated symptoms are tailored to individual needs. Regular follow-up with a neurologist and a multidisciplinary care team is essential for optimal management of the condition.
Repurposable Drugs: Currently, there are no well-established repurposable drugs specifically for Charcot-Marie-Tooth disease type 4H (CMT4H). CMT4H is a rare genetic disorder, and effective treatments are limited mainly to symptomatic management and supportive therapies, such as physical therapy, orthotic devices, and sometimes surgical interventions to correct deformities. Research is ongoing to find potential therapies, and any repurposable drugs would typically be identified through extensive clinical trials and studies. For up-to-date and specific information, consulting recent scientific literature or a healthcare professional specializing in genetic neuromuscular disorders is recommended.
Metabolites: For Charcot-Marie-Tooth Disease Type 4H (CMT4H), there is no specific set of altered metabolites universally associated with the disease. CMT4H is a form of peripheral neuropathy caused by mutations in the FGD4 gene. While metabolic testing is not a primary diagnostic approach for CMT4H, research may identify secondary metabolic changes in affected individuals. Comprehensive metabolic profiling or specific studies might provide insight into altered metabolites in the future, but as of now, no widely recognized metabolic markers are defined for CMT4H.
Nutraceuticals: For Charcot-Marie-Tooth Disease Type 4H, there is currently no specific nutraceutical treatment established. Management of the disease typically focuses on supportive measures such as physical therapy, occupational therapy, and sometimes orthopedic interventions to maintain mobility and function. It's important for patients to work closely with their healthcare provider for comprehensive care.
Peptides: Charcot-Marie-Tooth disease Type 4H (CMT4H) is a subtype of Charcot-Marie-Tooth disease, which is a hereditary disorder affecting peripheral nerves. CMT4H is specifically caused by mutations in the FGD4 gene. The use or investigation of peptides in relation to this condition is not well-documented in the current medical literature. If you need specific details about therapeutic approaches involving peptides, further specialized research or consultations with specialists in neurogenetics or molecular medicine may be required.