Charcot-Marie-Tooth disease axonal type 2T

Charcot-Marie-Tooth disease axonal type 2T (CMT2T) is a slowly progressive autosomal recessive sensorimotor peripheral neuropathy with onset in middle age [1]. This condition affects the peripheral nerves, leading to weakness and atrophy of muscles, as well as sensory loss and decreased deep-tendon reflexes [2].

The symptoms of CMT2T typically occur later in life compared to other forms of Charcot-Marie-Tooth disease, and can include distal weakness, atrophy, sensory loss, and variable foot deformity [3]. This condition is characterized by abnormalities in the axon, which extends from a nerve cell body to muscles or to sense organs [5].

CMT2T is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition [4]. The prevalence of CMT2T is estimated to be less than 1 in 1 million people [4].

It's worth noting that CMT2T is one of several subtypes of Charcot-Marie-Tooth disease, which are classified based on their inheritance pattern and other characteristics. In particular, CMT2T is distinct from the dominant forms of CMT, such as CMT2B, which is characterized by severe ulceration problems and is predominantly a sensory disorder [6].

Overall, CMT2T is a rare but serious condition that affects the peripheral nerves and can lead to significant muscle weakness and sensory loss.

Charcot-Marie-Tooth Disease Axonal Type 2T Signs and Symptoms

Charcot-Marie-Tooth (CMT) disease axonal type 2T is a rare genetic disorder that affects the peripheral nerves, leading to muscle weakness, atrophy, and sensory loss. The symptoms of CMT2T can vary in severity and progression, but here are some common signs and symptoms:

• Distal weakness: Muscle weakness starts in the distal muscles (farthest from the center of the body) and progresses to the proximal muscles (closer to the center of the body). [1]
• Muscle atrophy: As muscle weakness progresses, muscle wasting or atrophy can occur. [2]
• Sensory loss: Decreased sensitivity to touch, heat, and cold in the feet and lower legs is a common symptom. [4]
• Foot deformities: Foot deformities, such as high arches and bent toes, can occur due to muscle weakness and atrophy. [7]
• Gait disturbance: Difficulty walking or maintaining balance can be a symptom of CMT2T. [5]

Additional symptoms

Some individuals with CMT2T may experience additional symptoms, including:

• Babinski sign: A reflex that involves the toes curling upwards when the sole of the foot is stimulated.
• Distal sensory impairment: Decreased sensation in the distal muscles.
• Hypoplasia of the corpus callosum: Underdevelopment of the corpus callosum, a part of the brain that connects the two hemispheres.

References

[1] Context result 1: CMT2 is characterized by distal weakness, atrophy, sensory loss, decreased deep-tendon reflexes, and variable foot deformity. [2] Context result 2: The clinical presentation is similar to Type 1: distal weakness, muscle atrophy, sensory loss and foot deformities. [4] Context result 4: Oct 1, 2018 — People with Charcot-Marie-Tooth disease typically experience a decreased sensitivity to touch, heat, and cold in the feet and lower legs, but ... [5] Context result 5: Clinical features · Babinski sign · Distal sensory impairment · Gait disturbance · Hypoplasia of the corpus callosum · Intellectual disability · Peripheral axonal ... [7] Context result 7: What are the symptoms of Charcot-Marie-Tooth disease? · Weakness of your foot and lower leg muscles · Foot deformities, including a high arch and bent toes ( ...

Diagnostic Tests for Charcot-Marie-Tooth Disease Axonal Type 2T

Charcot-Marie-Tooth disease axonal type 2T (CMT2T) is a slowly progressive autosomal recessive sensorimotor peripheral neuropathy. Diagnostic tests are essential to confirm the clinical diagnosis of CMT2T.

• Electromyography (EMG): EMG and nerve conduction studies should be performed first if CMT disease is suggested [5]. Findings vary, depending on the type of CMT.
• Nerve Conduction Velocity Tests: These tests are used to measure the speed at which electrical signals travel through nerves. They can help confirm the diagnosis of CMT2T [6].
• Nerve Biopsy: In some cases, a nerve biopsy may be performed to confirm the diagnosis of CMT2T [6].
• Genetic Testing: Genetic testing is needed to pinpoint the exact CMT subtype, including CMT2T. This involves analyzing genes associated with Charcot-Marie-Tooth disease [7][8].

Other Diagnostic Tests

• Electromyography (EMG): EMG can help identify muscle damage and confirm the diagnosis of CMT2T.
• Nerve Conduction Studies: These studies measure the speed at which electrical signals travel through nerves, helping to confirm the diagnosis of CMT2T.

References

[5] Electromyography (EMG) and nerve conduction studies should be performed first if CMT disease is suggested. Findings vary, depending on the type [5]. [6] The clinical diagnosis is then confirmed by electrodiagnostic tests like electromyography and nerve conduction velocity tests, and sometimes by nerve biopsy [6]. [7] Genetic testing is needed to pinpoint the exact CMT subtype, but when signs and symptoms are consistent with CMT (the appropriate clinical [8]. [8] The Invitae Charcot-Marie-Tooth Disease Comprehensive Panel analyzes genes that are associated with Charcot-Marie-Tooth disease (CMT), a group of hereditary [7].

Current Status of Drug Treatment for CMT Type 2A

Unfortunately, there is no effective drug treatment available for Charcot-Marie-Tooth disease (CMT) type 2A, which is the predominant axonal subtype of CMT. According to a review on the treatment of CMT [13], previous studies have shown that ascorbic acid (AA), also known as Vitamin C, has yielded negative results in clinical trials for CMT1A patients.

Current Research and Emerging Therapies

However, research is ongoing to explore new therapeutic approaches for CMT. A recent review on the treatment of CMT [15] highlights the rapid evolution of the landscape, with several novel approaches providing encouraging results in preclinical studies and leading to clinical trials.

Some potential emerging therapies for CMT type 2A include:

• Gene therapy approaches, such as RNA-interference (RNAi) and non-viral intraperitoneal delivery of synthetic siRNA [11]
• Small molecule inhibitors, such as NMD670, which targets the skeletal muscle specific ClC-1 chloride ion channel [5]

Challenges in Developing Effective Treatments

The development of effective treatments for CMT is challenging due to the slow disease progression and high variability among patients. Additionally, the lack of accurate data on the prevalence of rare types of CMT, such as CMT3, CMT4, CMT5, CMT6, and CMT7 [12], further complicates the development of targeted therapies.

Conclusion

While there is currently no effective drug treatment available for CMT type 2A, ongoing research and emerging therapeutic approaches offer hope for future treatments. Further studies are needed to explore the potential of these novel approaches and to develop effective treatments for this debilitating disease.

References:

[5] Jun 17, 2024 — NMD670 is a first-in-class, muscle-targeted small molecule inhibitor. [11] Gene Therapy Approaches for CMT1A. RNA-interference (RNAi) has been one of the main targets in CMT1A gene therapies. [12] CMT2A is the predominant axonal subtype of Charcot–Marie–Tooth disease, accounting for approximately 4~7% of all cases. [13] A few years ago, a review on treatment of CMT would have been very brief, by stating that there is no effective drug for any CMT type and that the few trials conducted, testing ascorbic acid (AA) efficacy in CMT1A, yielded negative results [1–4]. [15] Introduction: Charcot-Marie-Tooth disease (CMT) and related neuropathies represent the most prevalent inherited neuromuscular disorders.

The differential diagnosis for Charcot-Marie-Tooth (CMT) disease, specifically the axonal type 2T, involves considering other conditions that may present with similar symptoms. According to various sources [6][8], some of these differentials include:

• Diabetic neuropathy: A condition caused by high blood sugar levels damaging nerve fibers, leading to numbness, tingling, and pain in the hands and feet.
• Chronic inflammatory demyelinating polyneuropathy (CIDP): An autoimmune disorder that causes inflammation and damage to the myelin sheath surrounding nerve fibers, resulting in muscle weakness and sensory loss.
• Acquired peripheral neuropathy: A condition caused by various factors such as toxins, infections, or metabolic disorders, leading to damage to peripheral nerves.

It's also worth noting that CMT disease can be classified into different types based on the underlying pathology [10]. In the case of CMT2, which includes type 2T, the axonal form is characterized by distal weakness, atrophy, sensory loss, decreased deep-tendon reflexes, and variable foot deformity [4].

When considering a differential diagnosis for CMT disease, it's essential to take into account the patient's medical history, family history, and physical examination findings. A positive family history can make CMT likely, and a pedigree can help elucidate the inheritance pattern [6].