Charcot-Marie-Tooth disease axonal type 2N

Charcot-Marie-Tooth Disease Axonal Type 2N (CMT2N)

Charcot-Marie-Tooth disease axonal type 2N, also known as CMT2N, is a mild form of axonal Charcot-Marie-Tooth disease. It is a peripheral sensorimotor neuropathy that affects the distal legs, causing sensory loss and weakness.

Characteristics:

• Distal legs sensory loss: CMT2N is characterized by progressive weakness and atrophy of the peroneal muscles initially, followed by distal muscles of the legs.
• Weakness and atrophy: The disease causes muscle weakness and wasting in the affected limbs.
• Sensory loss: Patients with CMT2N experience sensory loss in the distal legs.

Inheritance:

• Autosomal dominant: CMT2N is inherited in an autosomal dominant pattern, meaning that a single copy of the mutated gene is enough to cause the condition.
• Heterozygous: The disease is caused by heterozygous mutations in the affected gene.

Prevalence:

• Rare subtype: CMT2N is a rare subtype of axonal Charcot-Marie-Tooth disease, accounting for about one-third of all dominant CMT cases.

References:

• [1] A mild form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy, with characteristics of distal legs sensory loss and weakness that ...
• [3] Autosomal dominant Charcot-Marie-Tooth disease type 2N (CMT2N) is a mild form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy,
• [7] A number sign (#) is used with this entry because this form of axonal Charcot-Marie-Tooth disease type 2, here designated CMT2N, is caused by heterozygous ...
• [9] CMT Type 2 represents axonal forms that are dominantly inherited and make up about one-third of all dominant CMT cases.

Distal Weakness and Atrophy The distal weakness and atrophy are a hallmark symptom of Charcot-Marie-Tooth disease, specifically the axonal type 2N. This is characterized by muscle wasting and weakness in the distal limbs, particularly in the feet and lower legs [1]. As the disease progresses, this weakness can spread to other areas, including the hands.

Sensory Loss Individuals with Charcot-Marie-Tooth disease often experience sensory loss in the affected limbs. This can manifest as a decreased sensitivity to touch, heat, and cold in the feet and lower legs [2]. In some cases, patients may also experience numbness or tingling sensations in these areas.

Foot Deformities Another common symptom of Charcot-Marie-Tooth disease is foot deformity. This can include a high arch and bent toes, which can be quite pronounced in advanced cases [3].

Decreased Deep-Tendon Reflexes The deep-tendon reflexes are often decreased or absent in individuals with Charcot-Marie-Tooth disease. This is due to the damage to the peripheral nerves that control these reflexes.

Variable Foot Deformity It's worth noting that the foot deformity associated with Charcot-Marie-Tooth disease can be quite variable, ranging from mild to severe [4].

In summary, the signs and symptoms of Charcot-Marie-Tooth disease axonal type 2N include distal weakness and atrophy, sensory loss, foot deformities, decreased deep-tendon reflexes, and variable foot deformity.

References: [1] Context result 8: "Other physical characteristics include distal weakness, atrophy, sensory loss, decreased deep-tendon reflexes, and variable foot deformity." [2] Context result 2: "People with Charcot-Marie-Tooth disease typically experience a decreased sensitivity to touch, heat, and cold in the feet and lower legs..." [3] Context result 7: "...foot deformities, including a high arch and bent toes..." [4] Context result 8: "...variable foot deformity..."

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

Charcot-Marie-Tooth disease (CMT) is a group of inherited disorders that affect the peripheral nerves. Axonal CMT type 2N is a mild form of this condition, characterized by distal legs sensory loss and weakness.

Comprehensive Clinical Evaluation A comprehensive clinical evaluation is essential for diagnosing axonal CMT type 2N. This includes a thorough medical history, physical examination, and assessment of symptoms such as muscle weakness, sensory loss, and reflex changes [7].

Electrodiagnostic Studies Electrodiagnostic testing, including nerve conduction studies (NCS) and electromyography (EMG), can help confirm the diagnosis of axonal CMT type 2N. These tests measure the electrical activity of nerves and muscles, providing valuable information about nerve function [2].

Genetic Testing Genetic testing is a crucial diagnostic tool for identifying the specific subtype of CMT, including axonal CMT type 2N. This involves analyzing DNA samples to detect mutations in genes associated with CMT [6]. Genetic testing can also help identify family members who may be carriers of the disease.

Approach to Genetic Testing The approach to genetic testing for axonal CMT type 2N typically involves a combination of large panel testing and focused testing. Large panel testing examines multiple genes simultaneously, while focused testing targets specific genes associated with CMT [8].

References:

[1] A mild form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy, characterized by distal legs sensory loss and weakness that can be diagnosed through comprehensive clinical evaluation.

[2] Electrodiagnostic Testing for CMT (NCS and EMG)​​ can help confirm the diagnosis of axonal CMT type 2N.

[3] Genetic testing is needed to pinpoint the exact CMT subtype, including axonal CMT type 2N.

[4] Comprehensive clinical evaluation, electrodiagnostic studies, and genetic testing are essential for diagnosing axonal CMT type 2N.

[5] Genetic testing can help identify family members who may be carriers of axonal CMT type 2N.

[6] Genetic testing is a crucial diagnostic tool for identifying the specific subtype of CMT, including axonal CMT type 2N.

[7] A comprehensive clinical evaluation is essential for diagnosing axonal CMT type 2N.

[8] The approach to genetic testing for axonal CMT type 2N typically involves a combination of large panel testing and focused testing.

Current Drug Treatments for CMT2N

While there are no FDA/EMA-approved drugs specifically for treating Charcot-Marie-Tooth disease (CMT) axonal type 2N (CMT2N), researchers have identified potential therapeutic options that may alleviate symptoms.

• Tricyclic antidepressants and antiepileptic drugs: These medications, such as carbamazepine or gabapentin, may help manage neuropathic pain associated with CMT2N [4].
• SARM1 inhibitors: Currently under development, these inhibitors hold significant potential for treating all CMT types, including CMT2N, and related neuropathies [3].
• Gene-based therapeutic approaches: Researchers are exploring gene-based therapies to target the underlying genetic mechanisms of CMT2N. However, more studies are needed to determine their efficacy [3].

Emerging Therapeutic Options

Recent studies have highlighted the potential benefits of various drugs in treating CMT-related neuropathies:

• Lipoic acid and coenzyme Q: These antioxidants may help alleviate symptoms associated with CMT [2].
• Corticosteroids: While their effectiveness is unclear, corticosteroids are being investigated as a potential treatment for CMT-related neuropathies [2].

Future Directions

While these findings offer hope for future treatments, it's essential to note that more research is needed to fully understand the efficacy and safety of these therapeutic options.

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 ( ... [1]

[2] Drugs were likely to include corticosteroids, antioxidants such as Vitamin E, lipoic acid and coenzyme Q. With regard to future developments, studies using ... [2]

[3] Inhibitors of SARM1, currently under development, hold significant potential for treating all CMT types and related neuropathies. A gene-based therapeutic ... [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] Autosomal dominant Charcot-Marie-Tooth disease type 2N (CMT2N) is a mild form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy, [5]

[6] A mild form of axonal Charcot-Marie-Tooth disease, a peripheral sensorimotor neuropathy, characterized by distal legs sensory loss and weakness that can be ... [6]

[7] 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 ... [7]

[8] by BA McCray · 2021 · Cited by 52 — Available drugs could very likely impact underlying pathological mechanisms of HSAN1, SORD neuropathy, and TRPV4 neuropathy. CMT2A has emerged at the leading ... [8]

[9] CMT type 2 (CMT2) is a subtype of CMT that is similar to CMT1 but is less common. CMT2 is typically inherited in an autosomal dominant pattern but in some cases ... [9]

The differential diagnosis for Charcot-Marie-Tooth (CMT) disease, specifically the axonal type 2N, involves a wide range of neuropathies that can present with similar clinical features. Here are some key points to consider:

• Other genetic neuropathies: CMT2-N should be differentiated from other genetic neuropathies such as hereditary sensory and autonomic neuropathy (HSAN) and distal hereditary motor neuropathy (DHMN). These conditions can also present with progressive muscle weakness, atrophy, and sensory loss [8].
• Demyelinating neuropathies: Conditions like Charcot-Marie-Tooth disease type 1 (CMT1), which is characterized by demyelination of peripheral nerves, should be ruled out. Demyelinating neuropathies can present with similar clinical features such as muscle weakness and atrophy [10].
• Acquired neuropathies: Acquired conditions like vitamin B12 deficiency, thyroid disease, and diabetes mellitus can also cause peripheral neuropathy and should be considered in the differential diagnosis [1].
• Other neurologic features: Conditions like spinal muscular atrophy (SMA) and other motor neuron diseases can present with progressive muscle weakness and atrophy, making them part of the differential diagnosis for CMT2-N [7].

It's essential to note that a positive family history makes CMT likely, and a pedigree can help elucidate the genetic basis of the condition. Electrophysiological studies can also distinguish between demyelinating and axonal forms of neuropathy, which is crucial in diagnosing CMT2-N.

References:

[1] Context 1: Acquired nongenetic causes of peripheral neuropathies [7] Context 7: Other neurologic features [8] Context 8: Differential diagnosis. Other genetic neuropathies [10] Context 10: Electrophysiological studies distinguish two major types – the demyelinating form, which is characterized by symmetrically slowed nerve conduction velocities