Charcot-Marie-Tooth disease type 4C

Charcot-Marie-Tooth Disease Type 4C (CMT4C)

Charcot-Marie-Tooth disease type 4C, also known as CMT4C, is a subtype of Charcot-Marie-Tooth disease type 4. It is characterized by childhood or adolescent-onset of a relatively mild demyelinating neuropathy [1]. This condition affects the peripheral nerves and can cause symptoms such as foot deformities, sensory and motor neuropathy in the lower limbs, high arched or flat feet, and mild difficulty walking [3].

Key Features:

• Early onset: CMT4C typically presents in childhood or adolescence.
• Mild demyelinating neuropathy: This condition is characterized by a relatively mild loss of myelin sheath around the peripheral nerves.
• Sensory and motor symptoms: Patients often experience sensory and motor neuropathy in the lower limbs, which can lead to difficulties with walking and balance.
• Foot deformities: CMT4C can cause foot deformities such as high arched or flat feet.

Genetic Basis:

• Autosomal recessive inheritance: CMT4C is inherited in an autosomal recessive pattern, meaning that individuals must inherit two copies of the mutated gene (one from each parent) to develop the condition [2].
• SH3TC2 gene mutations: The SH3TC2 gene mutations are responsible for causing CMT4C [6].

References:

[1] Context result 1 [2] Context result 2 [3] Context result 3 [6] Context result 6

Charcot-Marie-Tooth disease type 4C (CMT4C) is a rare subtype of CMT, characterized by early-onset severe spine deformities, particularly scoliosis. The most affected individuals present with scoliosis, which can lead to significant morbidity and disability.

Common signs and symptoms:

• Early-onset severe spine deformities, including scoliosis
• Scoliosis is a sideways curvature of the spine that can cause discomfort, breathing difficulties, and other complications
• Cranial nerve involvement, leading to impairment of cranial nerves (e.g., facial weakness, hearing loss)
• Moderate to severe neuropathy, affecting motor and sensory functions
• Childhood onset, with symptoms typically appearing in early childhood

Other possible signs and symptoms:

• Decreased sensation or a loss of feeling in the legs and feet
• Muscle weakness, particularly in the distal muscles (those farthest from the center of the body)
• High foot arches (pes cavus) and hammertoes
• Difficulty lifting the foot at the ankle (footdrop)
• Awkward or higher than normal step (gait)
• Frequent tripping or falling

Important note:

CMT4C is a rare subtype of CMT, and its symptoms can vary widely among affected individuals. The severity and progression of symptoms can also differ significantly from person to person.

References:

[2] Common features of CMT4C include childhood onset, thoracic spine scoliosis, moderate to severe neuropathy, and cranial nerve deficits including impairment of cranial nerves. [3] A wide spectrum of nerve conduction velocities are observed and cranial nerve involvement and kyphoscoliosis have also been reported.

[5] The most common symptoms are walking difficulties with steppage gait or pes cavus. Hammer toes are frequent and other skeletal deformities, such as scoliosis, can occur.

[11] High foot arches. Curled toes (hammertoes) Decreased ability to run. Difficulty lifting your foot at the ankle (footdrop) Awkward or higher than normal step (gait) Frequent tripping or falling. Decreased sensation or a loss of feeling in your legs and feet.

[13] CMT can be divided into types and subtypes. The types are the clinical pictures of CMT (CMT type 1, 2, 4, X, etc.), usually defined by inheritance pattern and nerve conductions. Subtypes (CMT1A, 2B, 4C, X1, etc.) are given only when the genetic cause is known.

[14] The defining characteristic of Charcot-Marie-Tooth disease type 4 is that it has autosomal recessive inheritance. This means that an individual would need to have two copies of the affected disease-causing gene to develop symptoms.

Diagnostic Tests for Charcot-Marie-Tooth Disease Type 4C

Charcot-Marie-Tooth disease type 4C (CMT4C) is a subtype of Charcot-Marie-Tooth type 4, characterized by childhood or adolescent-onset of a relatively mild, demyelinating sensorimotor 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.

Diagnostic Tests:

• Nerve Conduction Studies (NCS): NCS were obtained routinely from the left ulnar motor nerve and left radial sensory nerve unless otherwise specified. Ulnar and radial nerve conduction velocities are observed to be variable [5].
• Electromyography (EMG): EMG should be performed first if CMT disease is suggested. Findings vary, depending on the type of CMT4C [8].
• Genetic Testing: Genetic testing may help confirm a clinical diagnosis, predict disease prognosis and progression, facilitate early detection of symptoms, inform family planning and genetic counseling, or promote enrollment in clinical trials [3].

Other Diagnostic Tests:

• Blood Sample Analysis: These tests can detect the most common genetic defects known to cause Charcot-Marie-Tooth disease. Genetic testing may give people with the disorder more information for family planning [11].
• Clinical Trials: Clinical trials determine if a new test or treatment for a disease is effective and safe. Researchers may ultimately uncover better ways to treat, prevent, diagnose, and understand human diseases [10].

References:

[3] These tests can detect the most common genetic defects known to cause Charcot-Marie-Tooth disease. Genetic testing may give people with the disorder more information for family planning.

[5] NCS were obtained routinely from the left ulnar motor nerve and left radial sensory nerve unless otherwise specified. Ulnar and radial nerve conduction velocities are observed to be variable.

[8] EMG should be performed first if CMT disease is suggested. Findings vary, depending on the type of CMT4C.

[10] Clinical trials determine if a new test or treatment for a disease is effective and safe. Researchers may ultimately uncover better ways to treat, prevent, diagnose, and understand human diseases.

[11] These tests can detect the most common genetic defects known to cause Charcot-Marie-Tooth disease. Genetic testing may give people with the disorder more information for family planning.

Current Status of Drug Treatment for CMT4C

Unfortunately, there is still no effective drug treatment available for Charcot-Marie-Tooth disease (CMT) type 4C. Current management relies on rehabilitation therapy, surgery for foot deformities, and other symptomatic treatments to alleviate the symptoms of the disease [6].

Research in Progress

However, researchers are actively exploring various treatment approaches, including gene silencing and gene replacement therapies, as well as small molecule treatments, which are currently in preclinical testing [4]. These emerging therapies aim to target the underlying genetic mutations that cause CMT4C.

Symptomatic Treatments

In the meantime, symptomatic treatments such as physical therapy and orthopedic management can help alleviate symptoms like musculoskeletal pain and neuropathic pain. Medications like acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) may be prescribed to manage musculoskeletal pain, while tricyclic antidepressants may be used to treat neuropathic pain [5].

Gene Therapy

Researchers are also investigating gene therapy as a potential treatment for CMT4C. This approach aims to correct the underlying genetic mutations that cause the disease, potentially leading to more effective and long-lasting symptom relief [8]. However, this area of research is still in its early stages.

Conclusion

While there is currently no effective drug treatment available for CMT4C, researchers are actively exploring various emerging therapies that may offer new hope for patients. Symptomatic treatments can help alleviate symptoms, but more research is needed to develop targeted and effective treatments for this disease.

References:

[4] Many treatment approaches, including gene silencing and gene replacement therapies, as well as small molecule treatments are currently in preclinical testing. [5] Neuropathic pain may respond to tricyclic antidepressants ... [6] There is still no effective drug treatment available for Charcot-Marie-Tooth disease (CMT). Current management relies on rehabilitation therapy, surgery for ... [8] Drug treatment for CMT primarily focuses on symptom relief, whereas gene therapy aims to ameliorate or potentially cure symptoms of CMT with minimal adverse ...

Charcot-Marie-Tooth (CMT)