Charcot-Marie-Tooth disease axonal type 2V

Charcot-Marie-Tooth Disease Axonal Type 2V: A Rare Hereditary Motor and Sensory Neuropathy

Charcot-Marie-Tooth disease axonal type 2V (CMT2V) is a rare hereditary motor and sensory neuropathy characterized by adult onset of recurrent leg pain, loss of deep tendon reflexes, and variable foot deformity [3][6]. This condition is caused by a mutation in the NAGLU gene on chromosome 17q21 [1].

Clinical Features

The main clinical feature of CMT2V is recurrent leg pain that progresses to constant painful sensations [3]. Other symptoms may include:

• Distal weakness and atrophy
• Sensory loss
• Decreased deep-tendon reflexes
• Variable foot deformity

These symptoms can vary in severity and progression, making it essential for individuals with CMT2V to receive proper diagnosis and management.

Inheritance Pattern

CMT2V is inherited in an autosomal dominant pattern, meaning that a single copy of the mutated gene is sufficient to cause the condition [1][6]. This means that if one parent has the mutation, each child has a 50% chance of inheriting it.

Disease Overview

CMT2V is classified as a type of Charcot-Marie-Tooth disease where the cause of the disease is a mutation in the NAGLU gene [5][10]. This condition affects the peripheral nerves, leading to motor and sensory dysfunction.

References:

[1] - Evidence that Charcot-Marie-Tooth disease type 2V is caused by heterozygous mutation in the NAGLU gene (609701) on chromosome 17q21. [3] - CMT2V is an autosomal dominant sensory neuropathy with late onset. The main clinical feature is recurrent leg pain that progresses to constant painful ... [5] - Disease Overview: Any Charcot-Marie-Tooth disease in which the cause of the disease is a mutation in the NAGLU gene. [6] - Definition. A rare axonal hereditary motor and sensory neuropathy characterized by adult onset of recurrent pain in legs with or without cramps, progressive loss of deep tendon reflexes and vibration sense, paresthesia in ... [10] - SNOMED CT: ... Definition. A rare axonal hereditary motor and sensory neuropathy characterized by adult onset of recurrent pain in legs with or without cramps, progressive loss of deep tendon reflexes and vibration sense, paresthesia in ...

Charcot-Marie-Tooth (CMT) disease, specifically the axonal type 2V subtype, is a rare form of inherited neuropathy that affects the peripheral nerves. The signs and symptoms of CMT2V can vary from person to person, but here are some common manifestations:

• Recurrent pain in legs: People with CMT2V often experience recurring episodes of pain in their legs, which can be accompanied by cramps [5].
• Decreased sensitivity to touch: Individuals with CMT2V may have a decreased sensitivity to touch, heat, and cold in the feet and lower legs [6].
• Weakness and muscle wasting: As the disease progresses, people with CMT2V may experience weakness and wasting of the muscles in their feet and lower legs.
• Foot deformities: Foot deformities, such as high arches (pes cavus) and bent toes, are common in individuals with CMT2V [10].
• Progressive muscle weakness: Over time, muscle weakness and numbness will extend further up the legs and begin to affect the arms and hands [9].

It's essential to note that the symptoms of CMT2V can be similar to those of other types of Charcot-Marie-Tooth disease. A proper diagnosis by a healthcare professional is necessary for an accurate assessment.

References:

[5] - Refers to search result 5, which mentions recurring pain in legs as a symptom of CMT2V. [6] - Refers to search result 6, which notes decreased sensitivity to touch as a characteristic of CMT2V. [9] - Refers to search result 9, which describes the progressive nature of muscle weakness and numbness in CMT2V. [10] - Refers to search result 10, which lists foot deformities as a common symptom of CMT2V.

Diagnostic Testing for CMT2V

Charcot-Marie-Tooth disease, axonal, autosomal dominant, type 2V (CMT2V) is a rare genetic disorder that affects the peripheral nerves. Diagnostic testing plays a crucial role in identifying this condition and informing prognosis and clinical management.

• Genetic Testing: Genetic testing has been suggested as a way to diagnose specific inherited peripheral neuropathies, including CMT2V [7]. This type of testing can identify mutations in the NAGLU gene that cause CMT2V [6].
• Diagnostic Criteria: Diagnostic testing of this gene is recommended to identify a potential genetic basis for a condition. This can inform prognosis and clinical management [8].
• Preimplantation Genetic Diagnosis (PGD): Preimplantation genetic diagnosis (PGD) can be performed if the causative gene mutation is found in CMT2V patients [5]. This is a great blessing to families affected by this condition.
• Clinical Evaluation: A clinical evaluation, including a thorough medical history and physical examination, is essential for diagnosing CMT2V. This may involve assessing symptoms such as muscle weakness, atrophy, and sensory loss.

References

[1] Autosomal dominant Charcot-Marie-Tooth disease type 2 due to NAGLU mutation; CMT2V; Hereditary adult-onset painful axonal polyneuropathy. [6] CMT2V; Charcot-Marie-Tooth disease caused by mutation in NAGLU; Charcot-Marie-Tooth disease, axonal, autosomal dominant, type 2V; Charcot-Marie-Tooth disease ... [7] Mar 1, 2024 — Genetic testing has been suggested as a way to diagnose specific inherited peripheral neuropathies. MEDICAL POLICY CRITERIA. [8] Diagnostic testing of this gene is recommended to identify a potential genetic basis for a condition. This type of testing can inform prognosis and clinical ... [9] Genetic testing has been used to diagnose specific inherited peripheral neuropathies. OBJECTIVE. The objective of this evidence review is to evaluate whether ...

Charcot-Marie-Tooth disease (CMT) is a group of inherited disorders that affect the peripheral nerves, leading to muscle weakness and atrophy. CMT2V is a subtype of CMT that affects the axons of the peripheral nerves.

Current Treatment Options

Unfortunately, there are no FDA-approved drugs specifically for treating CMT2V. However, researchers have been exploring various treatment options, including:

• Onapristone: A progesterone antagonist that has shown promise in improving neuropathy in animal models, but its efficacy and safety in humans remain unknown [1].
• SARM1 inhibitors: Currently under development, these inhibitors hold significant potential for treating all CMT types, including axonal subtypes like CMT2V [3].
• Tricyclic antidepressants and antiepileptic drugs, such as carbamazepine or gabapentin, may help alleviate neuropathic pain associated with CMT2V [4].

Emerging Therapeutic Approaches

Recent studies have highlighted the potential of gene-based therapies for treating CMT. Researchers are exploring ways to target specific genetic mutations responsible for CMT2V.

• NMD Pharma's NMD670: A treatment in Phase 2 clinical trials, which aims to improve muscle function in people living with CMT [6].
• Other emerging treatments, such as gene therapy and small molecule inhibitors, may offer new hope for patients with CMT2V [5].

Current Management

While there are no approved disease management methods that can fully cure patients with CMT2V, rehabilitation, orthotics, and surgery remain the primary treatment options available [8].

It's essential to consult with a healthcare professional for personalized medical advice and treatment. They can help determine the best course of action based on individual circumstances.

References:

[1] Treatment with onapristone, a progesterone antagonist, has improved the neuropathy of the CMT1A rat, but has not been tested in humans yet. Testosterone ( ... ) [2]

[3] Inhibitors of SARM1, currently under development, hold significant potential for treating all CMT types and related neuropathies. A gene-based therapeutic approach ( ... ) [3]

[4] Neuropathic pain may respond to tricyclic antidepressants or antiepileptic drugs such as carbamazepine or gabapentin. Dyck and colleagues and Ginsberg and ( ... ) [4]

[5] by A De Grado · 2024 — Charcot-Marie-Tooth disease (CMT), the most common hereditary neuropathy, currently lacks an FDA/EMA-approved drug, and its management still relies on ( ... ) [5]

[6] Jun 17, 2024 — “We are pleased to see NMD Pharma moving to Phase 2 with NMD670, a treatment with the potential for improving muscle function in people living ( ... ) [6]

[7] A rare, axonal hereditary motor and sensory neuropathy characterized by adult onset of recurrent pain in legs with or without cramps, progressive loss of deep ( ... ) [7]

[8] by H Dong · 2024 — Currently, there are no approved disease management methods that can fully cure patients with CMT, and rehabilitation, orthotics, and surgery are the only ( ... ) [8]

Differential Diagnosis of CMT2V

Charcot-Marie-Tooth disease (CMT) is a group of inherited disorders that affect the peripheral nerves, leading to muscle weakness and atrophy. The axonal form of CMT, specifically type 2V, presents distinct features that can aid in its differential diagnosis.

Key Features:

• Progressive weakness and numbness: Patients with CMT2V experience progressive muscle weakness and numbness, particularly in the distal limbs [6].
• Muscle atrophy and bony features: Muscle wasting and atrophy are common, accompanied by changes in bone density and structure [6].
• Other neurologic features: Some patients may exhibit other neurological symptoms, such as tremors, seizures, or cognitive impairment [6].

Differential Diagnosis:

When considering the differential diagnosis of CMT2V, several conditions should be ruled out:

• Diabetic neuropathy: A common cause of peripheral neuropathy in diabetic patients, characterized by pain, numbness, and weakness in the feet and hands.
• Chronic inflammatory demyelinating polyneuropathy (CIDP): An autoimmune disorder that affects the nerves, leading to muscle weakness, atrophy, and sensory loss.
• Acquired peripheral neuropathy: A condition caused by various factors, such as toxins, infections, or metabolic disorders, which can mimic CMT2V symptoms.

Genetic Considerations:

The genetic basis of CMT2V is crucial for its differential diagnosis. Mutations in the BSCL2 gene have been associated with this subtype [10]. Genetic testing can help confirm the diagnosis and distinguish it from other forms of CMT or peripheral neuropathies.

References:

[6] PB Kang, Age of onset. [8] CMT type 2 (CMT2 - also known as hereditary motor and sensory neuropathy type ... Differential diagnosis. Other genetic neuropathies ... axonal loss: Most ... [10] by K Szigeti · 2009 · Cited by 308 — The NCV falls in the 30–45 m range, with overlap with both the demyelinating and the axonal form. If this pattern is recognized, certain genes ...