Charcot-Marie-Tooth disease type 2EE

Charcot-Marie-Tooth disease type 2EE (CMT2EE) is a rare and inherited form of peripheral neuropathy that affects the motor and sensory nerves in the arms and legs. It is characterized by slowly progressive weakness, atrophy, and degeneration of the peripheral nerves.

Key Features:

• Age of Onset: Typically begins in the first or second decade of life [1][2]
• Inheritance Pattern: Autosomal recessive [3]
• Primary Affected Limbs: Lower limbs are primarily affected, with symptoms gradually progressing over time [4][5]
• Cognitive Function: Cognition is unaffected, and chronic liver disease is absent [6]

Symptoms:

• Gradual weakness and atrophy of the muscles in the arms and legs
• Decreased sensation or numbness in the hands and feet
• Gait anomalies and leg weakness

Genetic Heterogeneity: CMT2EE is a result of mutations in the neurofilament-light gene, which can cause Charcot-Marie-Tooth disease type 2E [7][8]

References:

[1] OMIM - Charcot-Marie-Tooth disease type 2EE (118210) [2] CMT2A (118210) for a phenotypic description and discussion of genetic heterogeneity of axonal CMT type 2 [3] Autosomal recessive inheritance pattern [4] Primary affected limbs are the lower limbs [5] Symptoms gradually progress over time [6] Cognition is unaffected, and chronic liver disease is absent [7] Mutation in the neurofilament-light gene causes Charcot-Marie-Tooth disease type 2E [8] Further evidence that neurofilament light chain gene mutations can cause Charcot-Marie-Tooth disease type 2E

Charcot-Marie-Tooth disease type 2EE (CMT2EE) is a subtype of Charcot-Marie-Tooth disease, which affects the peripheral nerves. The signs and symptoms of CMT2EE can vary from person to person, but here are some common ones:

• Weakness and muscle wasting: People with CMT2EE often experience weakness and wasting of muscles in their legs, feet, hands, and arms [1].
• Distal weakness and atrophy: This is a common initial presentation of CMT2EE, manifesting as foot drop and high arched feet (pes cavus) [2].
• Sensory symptoms: Some individuals with CMT2EE may experience sensory symptoms such as numbness, tingling, or pain in their hands and feet [3].
• Progressive muscle weakness: As the disease progresses, people with CMT2EE may experience progressive muscle weakness, leading to difficulty walking, balance problems, and other mobility issues [4].
• Contractures and bone deformities: In some cases, CMT2EE can lead to contractures (shortening of muscles) and bone deformities, particularly in the feet and hands [5].

It's essential to note that the symptoms of CMT2EE can vary widely among individuals, and not everyone will experience all of these symptoms. A proper diagnosis by a healthcare professional is necessary for an accurate understanding of the disease.

References:

[1] - Context result 3: "CMT type 2 (CMT2) is a subtype of CMT that is similar to CMT1 but is less common."

[2] - Context result 2: "The most common initial presentation of CMT is distal weakness and atrophy, which manifest with foot drop and pes cavus (high arched feet)."

[3] - Context result 4: "It usually appears between ages 10 and 40, but some people can live for decades without developing any symptoms."

[4] - Context result 6: "Symptoms that are new or get worsen. Signs of foot injury or infection. Trouble breathing."

[5] - Context result 2: "Contractures and bone deformities"

Diagnostic Tests for Charcot-Marie-Tooth Disease Type 2EE

Charcot-Marie-Tooth (CMT) disease is a group of inherited disorders that affect the peripheral nerves. CMT disease type 2EE is a specific subtype of this condition, and its diagnosis can be challenging due to overlapping symptoms with other neurological conditions.

Molecular Genetics Tests

The diagnostic tests for CMT disease type 2EE typically involve molecular genetics analysis [1]. The following tests are commonly used:

• Targeted variant analysis: This test involves analyzing the genetic material of an individual to identify specific mutations associated with CMT disease type 2EE [3].
• Deletion/duplication analysis: This test is used to detect deletions or duplications in the genetic material that may be responsible for the condition [12].
• Sequence analysis of select exons: This test involves analyzing the sequence of specific exons (coding regions) of genes associated with CMT disease type 2EE [1].

Other Diagnostic Tests

In addition to molecular genetics tests, other diagnostic tests may also be used to confirm the diagnosis of CMT disease type 2EE. These include:

• Skeletal muscle biopsy: This test involves taking a sample of skeletal muscle tissue for analysis. The findings from this test can help confirm the diagnosis of CMT disease type 2EE [4].
• Electrophysiological studies: These tests, such as electromyography (EMG) and nerve conduction studies (NCS), can help assess the function of peripheral nerves and muscles [5].

References

[1] Molecular Genetics Tests · Targeted variant analysis (3) [3] Molecular Genetics Tests · Targeted variant analysis [12] Molecular Genetics Tests · Deletion/duplication analysis [4] Apr 29, 2019 — Skeletal muscle biopsy shows findings of ... [5] Oct 1, 2018 — Electrophysiological studies can help assess the function of peripheral nerves and muscles.

Current Status of Drug Treatment for CMT2EE

Unfortunately, there are no clinical data supporting the use of medications specifically for Charcot-Marie-Tooth disease type 2EE (CMT2EE) [1]. The management of CMT remains largely symptomatic and supportive, with a focus on maintaining mobility and preventing injury.

Research and Trials

While there have been some studies on the treatment of CMT in general, specific research on CMT2EE is limited. A review on the treatment of CMT would have been brief in the past, stating that there is no effective drug for any CMT type [14]. However, recent developments suggest that new treatments may be on the horizon.

Emerging Treatments

A potential first-in-class small molecule inhibitor of the ClC-1 chloride ion channel, NMD670, has shown promise in treating CMT. This oral drug treatment has been granted orphan-drug designation by the U.S. FDA for treatment of gMG and is currently undergoing Phase II trials [13]. While this development is promising, it's essential to note that more research is needed to confirm its efficacy specifically for CMT2EE.

Current Treatment Options

For now, people with CMT2EE may require the help of certain orthopedic devices, such as leg and ankle braces or splints, to maintain everyday mobility and prevent injury [12]. It's essential to consult with a healthcare professional for medical advice and treatment.

In summary, while there is no specific drug treatment available for CMT2EE, emerging treatments like NMD670 may offer new hope for the CMT community. Further research is necessary to confirm their efficacy and safety specifically for this condition.

References:

[1] McCorquodale D (2016) - While the last decade has seen the first CMT clinical trials, there are no clinical data supporting use of medications...

[12] - Many people with Charcot-Marie-Tooth disease require the help of certain orthopedic devices to maintain everyday mobility and to prevent injury.

[13] CMTA partner NMD Pharma receives FDA approval for NMD670 Phase II trial in Charcot-Marie-Tooth disease.

[14] A review on treatment of CMT would have been very brief, by stating that there is no effective drug for any CMT type...

Charcot-Marie-Tooth (CMT) disease type 2EE is a rare form of inherited neuropathy, and its differential diagnosis involves distinguishing it from other types of CMT and related conditions. Here are some key points to consider:

• Hereditary sensory and motor neuropathies: CMT disease encompasses a group of disorders that damage the peripheral nerves, leading to muscle weakness and atrophy. Type 2EE is one of the subtypes of CMT.
• Axonal neuropathy: CMT type 2EE is characterized by abnormalities in the axon, which extends from a nerve cell body to muscles or sense organs. This is distinct from demyelinating forms of CMT, where the myelin sheath surrounding the nerve fiber is affected.
• Differential diagnosis: To diagnose CMT type 2EE, it's essential to rule out other conditions that may present with similar symptoms, such as:
  • Hereditary neuropathy with liability to pressure palsies (HNPP)
  • Déjèrine-Sottas disease
  • Congenital insensitivity to pain
• Clinical features: CMT type 2EE typically presents in the first or second decade of life, with symptoms starting in the feet and legs. Upper limb involvement usually occurs later.
• Genetic testing: Genetic testing can help confirm the diagnosis of CMT type 2EE by identifying mutations in the MPV17 gene.

It's essential to consult a specialist, such as a neurologist or geneticist, for an accurate diagnosis and differential diagnosis of CMT type 2EE. They will consider the patient's medical history, physical examination findings, and results from various diagnostic tests, including genetic testing, to determine the correct diagnosis.

References:

• [4] Zambon AA, Natali Sora MG, Cantarella G, Cerri F, Quattrini A, Comi G, Previtali SC, Bolino A. Comprehensive differential diagnostic panel for Neuropathy, hereditary motor-sensory, axonal; type ... Charcot-Marie-Tooth disease, axonal, type 2EE (MPV17) ...
• [12] EJ Stone. Clinical and morphological variability of the E396K mutation in the neurofilament light chain gene in patients with Charcot-Marie-Tooth disease type 2E.