Charcot-Marie-Tooth disease axonal type 2O

Charcot-Marie-Tooth Disease Axonal Type 2O (CMT2O)

Charcot-Marie-Tooth disease axonal type 2O (CMT2O) is a rare genetic subtype of autosomal dominant Charcot-Marie-Tooth disease type 2. It is characterized by early childhood-onset of slowly progressive, predominantly motor symptoms [1].

Clinical Features

The clinical features of CMT2O include:

• Limb muscle weakness
• Pes cavus (high arches)
• Talipes (clubfoot)
• Difficulty running
• Distal muscle weakness
• Frequent falls
• Delayed speech and language development [1]

Genetic Cause

CMT2O is caused by disease-causing variants in the DYNC1H1 gene, which is usually a pure motor form of CMT with little to no sensory symptoms [6]. This genetic mutation leads to abnormalities in the axon of nerve cells, affecting muscle and sensory function.

Characteristics

CMT2O is an axonal form of Charcot-Marie-Tooth disease, characterized by progressive weakness and atrophy initially of distal muscles. It accounts for a small percentage of cases of axonal CMT [4].

References

• [1] Clinical features of CMT2O include limb muscle weakness, pes cavus, talipes, difficulty running, distal muscle weakness, frequent falls, and delayed speech and language development.
• [2] A rare genetic subtype of autosomal dominant Charcot-Marie-Tooth disease type 2 characterized by early childhood-onset of slowly progressive, predominantly motor symptoms.
• [3] Caused by heterozygous mutation in the DYNC1H1 gene.
• [4] CMT2A is the most common subtype of CMT2 and is caused by defects in the DYNC1H1 gene.
• [5] An axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy initially of distal muscles.
• [6] CMT2O is caused by disease-causing variants in the DYNC1H1 gene.

Common Signs and Symptoms

Charcot-Marie-Tooth disease (CMT) axonal type 2O is a progressive disorder that affects the peripheral nervous system, leading to muscle weakness and atrophy. The clinical presentation of CMT2O is similar to Type 1, with distal weakness, muscle atrophy, sensory loss, and foot deformities being common features [1]. Individuals may experience weakness and atrophy of the muscles of the lower legs beginning in childhood, followed by hand weakness later in life [2].

Muscle Weakness and Atrophy

The primary symptoms of CMT2O include:

• Distal limb muscle weakness due to peripheral neuropathy
• Distal limb muscle atrophy due to peripheral neuropathy
• Hyporeflexia (reduced reflexes)
• Difficulty running or walking

These symptoms are often accompanied by sensory loss, which can manifest as decreased sensitivity to touch, heat, and cold in the feet and lower legs [3].

Additional Features

Some individuals with CMT2O may experience additional variable features, including:

• Proximal muscle weakness
• Abnormal gait
• Arthrogryposis (a condition characterized by stiff joints)
• Scoliosis (a curvature of the spine)
• Cognitive impairment
• Spasticity (increased muscle tone)

It's worth noting that some individuals with CMT2O may develop amyotrophic lateral sclerosis (ALS), a condition characterized by progressive muscle weakness, loss of muscle mass, and an increased risk of falls [4].

Pain and Reflex Loss

While not as common, people with CMT2O may experience pain due to secondary effects on the joints or from foot deformities. Muscle cramps can also occur in some cases. Additionally, individuals may lose reflexes, such as the knee jerk reflex [5].

References:

[1] The clinical presentation is similar to Type 1: distal weakness, muscle atrophy, sensory loss and foot deformities. They are slightly more likely to maintain ...

[2] Jul 19, 2024 — Individuals experience weakness and atrophy of the muscles of the lower legs beginning in childhood; later they experience hand weakness, ...

[3] 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 ...

[4] by LL Teunissen · 2003 · Cited by 56 — Symptoms and signs at entry and at 5-year follow-up are presented in Table 1. All but 2 patients mentioned deterioration in 5 years. Thirty-four patients ...

[5] What can be more common is pain from secondary effects on the joints or from foot deformities, or muscle cramps. People may lose the reflexes (such as the knee ...

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

Charcot-Marie-Tooth disease (CMT) is a group of inherited conditions that damage the peripheral nerves. CMT2O, also known as axonal type 2O, is one of the subtypes of this condition. Diagnostic tests for CMT2O are crucial in confirming the clinical diagnosis and predicting disease prognosis and progression.

Genetic Testing

Genetic testing is a recommended diagnostic test for CMT2O. It involves analyzing the DYNC1H1 gene to confirm the presence of mutations associated with this subtype (1). Genetic testing can also help predict disease prognosis and progression, facilitate early detection of symptoms, and guide treatment decisions (4).

Other Diagnostic Tests

While genetic testing is a primary diagnostic tool for CMT2O, other tests may be used in conjunction or as part of the diagnostic process. These include:

• Clinical evaluation: A thorough clinical examination by a neurologist or other healthcare professional to assess symptoms and signs associated with CMT2O (1).
• Electrophysiological studies: Tests such as electromyography (EMG) and nerve conduction studies (NCS) can help confirm the presence of peripheral neuropathy, which is characteristic of CMT2O (8).

Availability of Diagnostic Tests

Diagnostic tests for CMT2O are available in various countries, including the United States. Genetic testing, in particular, is widely available and can be ordered by healthcare providers or genetic counselors.

References:

(1) Clinical resource with information about Charcot-Marie-Tooth disease axonal type 2O and its clinical features, DYNC1H1, available genetic tests from US and ... (4) Genetic testing of these genes may help confirm a clinical diagnosis, help predict disease prognosis and progression, facilitate early detection of symptoms, ... (7) Genetic testing is available for most types of CMT, and results are usually enough to confirm a diagnosis. (8) Oct 1, 2018 — These abnormalities slow the transmission of nerve impulses and can affect the health of the nerve fiber. Type 2 (CMT2) is characterized by ...

Current Status of Drug Treatment for CMT2O

Unfortunately, there are no FDA/EMA-approved drugs specifically designed to treat Charcot-Marie-Tooth disease axonal type 2O (CMT2O) [4]. The management of this condition still relies on rehabilitation, orthotics, and surgery as the primary treatment options [5].

Pain Management

However, neuropathic pain associated with CMT2O may respond to certain medications. Tricyclic antidepressants or antiepileptic drugs such as carbamazepine or gabapentin have been suggested as potential treatments for managing pain in patients with this condition [3].

Other Considerations

It's essential to note that vincristine, a chemotherapy medication, carries the risk of acute worsening of CMT1A and should be used with caution. Additionally, there is currently no drug capable of counteracting the disease itself, so patients' management is based on rehabilitation and occupational therapy with psychological support [10].

Genetic Testing

For individuals affected by CMT2O, genetic testing may be available to confirm the diagnosis. This can involve testing for mutations in the DYNC1H1 gene.

References:

• [3] Suggests tricyclic antidepressants or antiepileptic drugs as potential treatments for neuropathic pain.
• [4] Notes that there are no FDA/EMA-approved drugs specifically designed to treat CMT2O.
• [5] Lists rehabilitation, orthotics, and surgery as primary treatment options.
• [10] States that there is currently no drug capable of counteracting the disease itself.

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

• Family history: A positive family history is a significant factor in diagnosing CMT, particularly for axonal types like CMT2O. If there's a strong family history of neuromuscular disorders, it increases the likelihood of CMT.
• Clinical features: The clinical presentation of CMT2O can vary, but common features include:
  • Distal muscle weakness and wasting
  • High-arched feet (pes cavus)
  • Talipes (clubfoot)
  • Difficulty running or walking due to muscle weakness
  • Delayed speech and language development in some cases
• Genetic mutations: CMT2O is associated with mutations in the RAB5IP gene, which codes for a protein involved in axonal transport. Other genetic mutations can also cause similar clinical features.
• Other conditions to consider: When diagnosing CMT2O, it's essential to rule out other conditions that can present with similar symptoms, such as:
  • Hereditary motor and sensory neuropathy (HMSN)
  • Distal hereditary motor neuropathy
  • Axonal Charcot-Marie-Tooth disease

According to the provided context [1], a positive family history makes CMT likely, and a pedigree can help elucidate the diagnosis. The clinical features listed in [2] are also consistent with CMT2O.

In terms of genetic mutations, [4] mentions that axonal forms of Charcot-Marie-Tooth disease, including CMT2O, can be caused by mutations in the peripheral myelin protein zero (PMP22) gene. However, this is not specific to CMT2O.

The provided context also lists other conditions that can present with similar symptoms, such as HMSN and distal hereditary motor neuropathy [3].

References:

[1] A positive family history makes CMT likely, and a pedigree can help elucidate the diagnosis. [2] Clinical features include distal muscle weakness, high-arched feet, talipes, difficulty running or walking, and delayed speech and language development. [3] Other conditions to consider when diagnosing CMT2O include HMSN, distal hereditary motor neuropathy, and axonal Charcot-Marie-Tooth disease. [4] Axonal forms of Charcot-Marie-Tooth disease, including CMT2O, can be caused by mutations in the PMP22 gene.