Charcot-Marie-Tooth disease axonal type 2S

Charcot-Marie-Tooth disease (CMT) type 2S is a rare form of autosomal recessive axonal neuropathy that affects the peripheral nerves. It is characterized by:

• Onset in childhood: Symptoms typically appear in the first decade of life, with slow progression over time [1][2].
• Axonal involvement: The disease primarily affects the axons, which are the long, thin extensions of nerve cells that transmit signals to muscles or sensory organs [5].
• Relatively pure form: CMT type 2S is considered a relatively pure form of autosomal recessive axonal neuropathy, meaning it is less likely to be associated with other systemic symptoms [1][2][6].

It's worth noting that CMT type 2S is a rare condition, and its prevalence is estimated to be less than 1 in 1 million people [3]. The disease is inherited in an autosomal recessive pattern, meaning that both parents must carry the mutated gene for their child to inherit it [4].

References:

[1] Context result 1: Charcot-Marie-Tooth disease type 2S is a relatively pure form of autosomal recessive axonal neuropathy characterized by onset in the first decade of slowly ...

[2] Context result 6: Charcot-Marie-Tooth disease type 2S is a relatively pure form of autosomal recessive axonal neuropathy characterized by onset in the first decade of slowly ...

[3] Context result 3: Prevalence: <1 / 1 000 000

[4] Context result 3: Inheritance: Autosomal recessive

[5] Context result 5: Type 2 (CMT2) is characterized by abnormalities in the fiber, or axon, that extends from a nerve cell body to muscles or to sense organs.

[6] Context result 8: Charcot-Marie-Tooth disease type 2S is a relatively pure form of autosomal recessive axonal neuropathy characterized by onset in the first decade of slowly ...

Distal Weakness and Atrophy The signs and symptoms of Charcot-Marie-Tooth disease, specifically the axonal type 2S (CMT2S), include distal weakness and atrophy. This means that individuals with CMT2S experience muscle wasting and weakness in their hands and feet, starting from a young age [1]. The distal muscles, which are located farthest from the center of the body, are primarily affected.

Muscle Atrophy and Sensory Loss In addition to distal weakness, people with CMT2S also experience muscle atrophy, which is the wasting away of muscle tissue. This can lead to a decrease in muscle mass and strength [3]. Furthermore, sensory loss is another common symptom of CMT2S, where individuals may experience decreased sensitivity to touch, heat, and cold in their feet and lower legs [4].

Variable Foot Deformity CMT2S also often presents with variable foot deformities. This can include a high arch or bent toes, which are caused by the muscle weakness and atrophy in the feet [7]. The severity of these deformities can vary from person to person.

Progressive Nature It's essential to note that CMT2S is a progressive condition, meaning that symptoms will continue to worsen over time. This can lead to significant disability if left untreated or undertreated.

References: [1] - Context result 1 [3] - Context result 3 [4] - Context result 4 [7] - Context result 7

Diagnostic Tests for Charcot-Marie-Tooth Disease Axonal Type 2S (CMT2S)

Charcot-Marie-Tooth disease axonal type 2S (CMT2S) is a rare and inherited peripheral neuropathy. Diagnostic tests play a crucial role in confirming the clinical diagnosis, predicting disease prognosis and progression, facilitating early detection of symptoms, informing family planning and genetic counseling, or promoting enrollment in clinical trials.

Laboratory Tests

• Genetic testing: This involves analyzing DNA from a blood sample to identify mutations in the IGHMBP2 gene, which is responsible for CMT2S. [1][4]
• Nerve conduction studies (NCS): These tests measure the speed and strength of electrical signals traveling through nerves. Abnormal results can indicate nerve damage or dysfunction. [7]

Clinical Presentation

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

These symptoms are often first noticed in the lower legs, with foot drop, altered gait, hammertoes, high arches, and numbness/tingling being common presentations. [13]

Other Diagnostic Tests

• Family history: A thorough family history can provide clues about inherited conditions.
• Clinical presentation: A detailed medical history and physical examination are essential for diagnosing CMT2S.

Genetic Testing for Inherited Conditions

Recent advances in genetic testing have made it more affordable and comprehensive. Genetic testing may give people with the disorder more information for family planning, rule out other neuropathies, or confirm a clinical diagnosis. [12]

References:

[1] - CMT2S is caused by a mutation in the IGHMBP2 gene. [4] - Genetic testing of these genes may help confirm a clinical diagnosis... [7] - In addition to genetic testing, nerve conduction studies (NCS) can be used to diagnose CMT2S. [12] - Recent advances in genetic testing have made it more affordable and comprehensive. [13] - The initial symptoms of Charcot-Marie-Tooth disease are usually first noticed when an individual develops lower leg weakness and foot drop...

Current Status of Drug Treatment for CMT Type 2S

Charcot-Marie-Tooth disease (CMT) is a group of inherited disorders that affect the peripheral nerves. Among its various subtypes, CMT Type 2S is an axonal form characterized by progressive distal muscle weakness and atrophy [7]. Despite significant research efforts, there is currently no FDA/EMA-approved drug specifically targeting this subtype.

Investigational Therapies

However, recent developments offer hope for potential treatments. In February 2024, the U.S. FDA approved an Investigational New Drug (IND) application for a treatment aimed at CMT Type 2S [9]. Additionally, in February 2023, Orphan Drug Designation was granted by the FDA for VCA-894A, a compound being developed to treat this condition [10].

Other Therapeutic Options

While specific treatments for CMT Type 2S are still under investigation, other therapeutic approaches may provide some relief. Nonsteroidal anti-inflammatory drugs (NSAIDs), Cyclooxygenase-2 inhibitors, Tricyclic antidepressants, and physical therapy have been explored as potential management strategies [4][5].

Future Directions

Research into SARM1 inhibitors holds promise for treating all CMT types, including Type 2S. Gene-based therapeutic approaches are also being investigated to target specific mutations causing this condition [3]. A patient-specific cryptic splice site variant within immunoglobulin mu-binding protein 2 is another area of research focus [6].

References

• [1] Venlafaxine (Effexor) has been studied for its potential in treating neuropathic pain, which may be relevant to CMT Type 2S.
• [3] Inhibitors of SARM1 are being developed as a potential treatment for all CMT types, including Type 2S.
• [4] Nonsteroidal anti-inflammatory drugs (NSAIDs) have been explored as a management strategy for CMT.
• [5] Physical therapy and moderate activity have been shown to help maintain muscle function in patients with CMT.
• [6] Research is being conducted on gene-based therapeutic approaches targeting specific mutations causing CMT Type 2S.
• [7] CMT Type 2S is characterized by progressive distal muscle weakness and atrophy of both the lower and upper limbs.
• [8] Charcot-Marie-Tooth disease (CMT) currently lacks an FDA/EMA-approved drug, and its management still relies on symptomatic treatments.

The differential diagnosis for Charcot-Marie-Tooth (CMT) disease, specifically the axonal type 2S, involves a range of conditions that can present with similar symptoms. Here are some of the key differentials:

• Diabetic neuropathy: This is a common condition characterized by nerve damage due to high blood sugar levels. It can cause numbness, tingling, and pain in the hands and feet, which may be similar to the symptoms seen in CMT2S.
• Chronic inflammatory demyelinating polyneuropathy (CIDP): This is a rare autoimmune disorder that affects the nerves, causing muscle weakness, fatigue, and numbness. While CIDP typically presents with more widespread nerve involvement, it can be challenging to distinguish from CMT2S in some cases.
• Acquired peripheral neuropathy: This term refers to any type of nerve damage that occurs outside of a genetic or inherited context. Acquired peripheral neuropathies can cause a range of symptoms, including numbness, tingling, and pain in the hands and feet.

It's essential to note that CMT2S is a relatively pure form of autosomal recessive axonal neuropathy, characterized by onset in the first decade of slowly progressive distal muscle weakness and atrophy affecting both lower and upper limbs. Patients with CMT2S typically have decreased reflexes and variable distal sensory impairment.

When considering the differential diagnosis for CMT2S, it's crucial to take a comprehensive medical history, perform a thorough physical examination, and consider laboratory tests to rule out other conditions that may be causing similar symptoms. A positive family history of CMT can also help support the diagnosis.

References:

• [10] Charcot-Marie-Tooth disease type 2S is a relatively pure form of autosomal recessive axonal neuropathy characterized by onset in the first decade of slowly progressive distal muscle weakness and atrophy affecting both lower and upper limbs. Patients have decreased reflexes and variable distal sensory impairment (summary by Cottenie et al., 2014).
• [9] May 9, 2024 — Differentials · Diabetic neuropathy · Chronic inflammatory demyelinating polyneuropathy · Acquired peripheral neuropathy.
• [8] CMT type 2 (CMT2 - also known as hereditary motor and sensory neuropathy type ... Differential diagnosis. Other genetic neuropathies. Friedreich's ataxia ...