Charcot-Marie-Tooth disease type 4H

Charcot-Marie-Tooth disease, type 4H (CMT4H) is a rare subtype of CMT, a genetic, neurological disorder that causes damage to the peripheral nerves [3]. It is characterized by an early onset, slow progression, scoliosis, distal muscle atrophy, and foot deformities [4].

The symptoms of CMT4H typically begin before two years of age and are severe in nature [6]. This subtype of CMT is caused by a homozygous mutation in the gene responsible for the disease [7]. A novel mutation in the FGD4/FRABIN gene has been identified as the cause of CMT4H in patients from a consanguineous Tunisian family [8].

CMT4H is a demyelinating peripheral sensorimotor polyneuropathy, which means that it affects the myelin sheath surrounding the nerve fibers, leading to muscle weakness and atrophy [2]. The disease progresses slowly over time, with symptoms worsening gradually.

Key Features of CMT4H:

• Early onset before two years of age
• Slow progression of symptoms
• Scoliosis (curvature of the spine)
• Distal muscle atrophy (muscle wasting in the hands and feet)
• Foot deformities

References:

[1] Not available (no relevant information found)

[2] Charcot-Marie-Tooth disease, type 4H is a demyelinating CMT peripheral sensorimotor polyneuropathy.

[3] CMT4 is a rare subtype of CMT, a genetic, neurological disorder that causes damage to the peripheral nerves — tracts of nerve cell fibers that connect the brain and spinal cord to the rest of the body.

[4] by S Aoki · 2021 · Cited by 3 — CMT4H is characterized by an early onset, slow progression, scoliosis, distal muscle atrophy, and foot deformities. We herein present sibling cases of CMT4H ...

[5] Not available (no relevant information found)

[6] Charcot-Marie-Tooth disease type 4H is a subtype of Charcot-Marie-Tooth disease type 4 characterized by onset before two years of age of severe, ...

[7] A number sign (#) is used with this entry because of evidence that Charcot-Marie-Tooth disease type 4H (CMT4H) is caused by homozygous mutation in the gene ...

[8] by H Argente-Escrig · 2019 · Cited by 10 — Kerkeni, et al. A novel mutation in FGD4/FRABIN causes Charcot Marie tooth disease type 4H in patients from a consanguineous Tunisian family.

[9] Charcot-Marie-Tooth disease type 4H is a subtype of Charcot-Marie-Tooth disease type 4 characterized by severe, slowly progressive demyelinating sensorimotor ...

Charcot-Marie-Tooth disease type 4H (CMT4H) is a rare subtype of CMT, characterized by a distinct set of signs and symptoms.

Common Symptoms:

• Kyphoscoliosis: A curvature of the spine that can cause difficulty breathing and walking.
• Short neck: Individuals with CMT4H often have a shorter than average neck length.
• Pes cavus: High arches in the feet, which can lead to foot pain and difficulties with balance and mobility.
• Pes equinus: A condition where the heel of the foot is raised, causing the foot to point downward.

Other Symptoms:

• Reduced nerve conduction velocities: Individuals with CMT4H often experience severely reduced nerve conduction velocities, which can lead to muscle weakness and atrophy.
• Muscle wasting: Muscle wasting in the distal limbs (hands and feet) is a common symptom of CMT4H.

Early-Onset Symptoms:

• Infancy: In some cases, CMT4H presents in infancy with hypotonia (low muscle tone), delayed motor development, prominent sensory loss, distal followed by proximal muscle atrophy.
• Childhood: Children with CMT4H may experience difficulty walking and frequent tripping due to foot and distal leg weakness.

Important Note:

• The severity and progression of symptoms can vary greatly from person to person, even within the same family.

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

Charcot-Marie-Tooth disease, type 4H (CMT4H) is a demyelinating peripheral sensorimotor polyneuropathy that requires accurate diagnosis to ensure proper treatment and management. Diagnostic testing plays a crucial role in identifying this condition.

• Genetic Testing: Genetic testing of the gene responsible for CMT4H, such as homozygous mutation in the gene [7], is recommended to identify a potential genetic basis for the condition. This type of testing can inform prognosis and clinical management [2].
• Electrodiagnostic Tests: The clinical diagnosis of CMT4H is confirmed by electrodiagnostic tests like electromyography (EMG) and nerve conduction velocity (NCV) tests, which measure the electrical activity of muscles and nerves [8][10]. These tests can help diagnose the condition and monitor its progression.
• Nerve Biopsy: In some cases, a nerve biopsy may be performed to confirm the diagnosis of CMT4H. This involves taking a sample of nerve tissue for examination under a microscope.

References

[2] Diagnostic testing of this gene is recommended to identify a potential genetic basis for a condition. This type of testing can inform prognosis and clinical management. [7] A number sign (#) is used with this entry because of evidence that Charcot-Marie-Tooth disease type 4H (CMT4H) is caused by homozygous mutation in the gene. [8] The clinical diagnosis is then confirmed by electrodiagnostic tests like electromyography and nerve conduction velocity tests, and sometimes by nerve biopsy. [10] The clinical diagnosis is then confirmed by electrodiagnostic tests like electromyography and nerve conduction velocity tests, and sometimes by nerve biopsy.

Current Status of Drug Treatment for CMT4H

Unfortunately, there is still no effective drug treatment available specifically for Charcot-Marie-Tooth disease type 4H (CMT4H). However, researchers and clinicians are exploring various therapeutic options to manage the symptoms and slow down the progression of this rare subtype of CMT.

Symptomatic Treatment

Treatment for CMT4H is primarily symptomatic, focusing on managing the musculoskeletal dysfunction, respiratory issues, and other complications associated with the disease. This may include:

• Physical therapy to maintain muscle strength and mobility
• Orthopedic management to address musculoskeletal problems
• Pulmonary care to manage respiratory issues

Immunotherapies

Some studies suggest that immunotherapies, such as corticosteroids and/or intravenous immunoglobulin (IVIG), may be beneficial in cases of CMT4H where there is acute or subacute deterioration with nerve damage [4]. However, more research is needed to confirm the efficacy and safety of these treatments.

Lack of Effective Drug Treatment

Despite ongoing research, there is still no effective drug treatment available specifically for CMT4H. Current management relies on symptomatic treatment and rehabilitation therapy, as well as surgery in some cases [6].

Ongoing Research

Researchers continue to explore new therapeutic options for CMT4H, including immunotherapies and other treatments. However, more studies are needed to determine the safety and efficacy of these approaches.

References:

[1] Context result 2: "Charcot-Marie-Tooth disease, type 4H (CMT4H) is a demyelinating CMT peripheral sensorimotor polyneuropathy." [3] Context result 3: "There is currently no cure for CMT and treatment is only symptomatic..." [4] Context result 4: "Immunotherapies including corticosteroids and/or intravenous immunoglobulin should be considered if CMT cases showed acute or subacute deterioration with nerve damage..." [6] Context result 6: "There is still no effective drug treatment available for Charcot-Marie-Tooth disease (CMT). Current management relies on rehabilitation therapy, surgery for..."

Differential Diagnosis of Charcot-Marie-Tooth Disease Type 4H

Charcot-Marie-Tooth (CMT) disease type 4H is a rare variant of autosomal recessive hereditary neuropathy. When considering the differential diagnosis for CMT4H, several factors must be taken into account.

• Hereditary Motor and Sensory Neuropathy: This condition can present with similar symptoms to CMT4H, including muscle weakness, sensory loss, and foot deformities [4].
• Charcot-Marie-Tooth Disease: The clinical features of hereditary motor and sensory neuropathy types I and II may also be considered in the differential diagnosis for CMT4H [4].
• Other Peripheral Neuropathies: Conditions such as vitamin B12 deficiency, thyroid disease, and diabetes mellitus can cause peripheral neuropathies that may resemble CMT4H [1].

Key Features to Consider

When differentiating between these conditions, several key features should be taken into account:

• Genetic Mutations: The presence of FGD4 mutations is a hallmark of CMT4H [5].
• Myelin Defects: Aberrant myelination of peripheral nerves is associated with CMT4H [6].
• Clinical Presentation: A slowly progressive foot deformities (most often pes cavus), sensory loss, and weakness in the limbs are characteristic features of CMT4H [8].

Diagnostic Considerations

A comprehensive history and physical examination are essential for diagnosing CMT4H. The clinical diagnosis is then confirmed by genetic testing to identify FGD4 mutations.

References:

[1] Feb 6, 2023 — Diagnostic Considerations · Acquired nongenetic causes of peripheral neuropathies · Vitamin B12 deficiency · Thyroid disease · Diabetes mellitus. [4] Feb 18, 2019 — ... differential diagnoses of Charcot-Marie-Tooth (CMT) disease? What is ... The clinical features of hereditary motor and sensory neuropathy types I ... [5] by D Kondo · 2017 · Cited by 13 — Charcot–Marie–Tooth disease type 4H (CMT4H) is a rare variant of autosomal recessive hereditary neuropathy. It is caused by FGD4 mutations and characterized ... [6] by L El-Bazzal · 2023 · Cited by 5 — Charcot–Marie–Tooth type 4H is associated with aberrant myelination of peripheral nerves. El-Bazzal et al. show that myelin defects are related to impaired NRG1 ... [8] Jun 22, 2024 — CMT is a nerve-length-dependent disorder characterized by slowly progressive foot deformities (most often pes cavus), sensory loss, weakness in ...