Charcot-Marie-Tooth disease type 2B2

Charcot-Marie-Tooth Disease Type 2B2 (CMT2B2)

Charcot-Marie-Tooth disease type 2B2, also referred to as CMT4C3, is a rare and inherited form of peripheral neuropathy. It is characterized by progressive weakness and atrophy in the distal muscles of the limbs [1][7]. This condition affects the axons of the peripheral nerves, leading to muscle wasting and weakness, particularly in the hands and feet.

Key Features:

• Autosomal Recessive Inheritance: CMT2B2 is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition [2][7].
• Distal Muscle Weakness and Atrophy: The disease manifests as progressive weakness and atrophy in the distal muscles of the limbs, particularly in the hands and feet [1][3][6][9].
• Sensorineural Axonal Peripheral Neuropathy: CMT2B2 is a type of sensorineural axonal peripheral neuropathy, which affects the axons of the peripheral nerves [2][7].

References:

[1] - A recessive axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy, is described in search result 5. [2] - Charcot-Marie-Tooth disease type 2B2 (CMT2B2) is an autosomal recessive sensorineural axonal peripheral neuropathy manifest as distal muscle weakness and atrophy, is mentioned in search results 2 and 7. [3] - Charcot-Marie-Tooth disease, type 2B2 (CMT2B2, also referred to as CMT4C3) is an axonal CMT peripheral sensorimotor polyneuropathy that has been described in a large consanguineous Costa Rican family of Spanish ancestry, is mentioned in search results 1 and 6. [7] - Charcot-Marie-Tooth disease type 2B2 (CMT2B2) is an autosomal recessive sensorineural axonal peripheral neuropathy manifest as distal muscle weakness and atrophy, is mentioned in search result 7. [9] - CMT2B2 is a form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive muscle weakness and atrophy, is mentioned in search result 9.

Common Signs and Symptoms of Charcot-Marie-Tooth Disease Type 2B2

Charcot-Marie-Tooth disease type 2B2 is a progressive neurological disorder that affects the peripheral nerves. The signs and symptoms of this condition can vary from person to person, but here are some common ones:

• Distal limb muscle weakness: This is one of the most common symptoms of CMT2B2, affecting the muscles in the hands and feet [1].
• Hyporeflexia: A decrease in reflexes, particularly in the distal limbs [2].
• Steppage gait: A gait abnormality where patients take larger steps to compensate for muscle weakness [2].
• Areflexia: The absence of reflexes in the affected limbs [2].
• Distal sensory impairment: Patients may experience numbness or tingling sensations in their hands and feet [6].
• Progressive loss of ambulation: Over time, patients with CMT2B2 may lose independent ambulation due to muscle weakness and atrophy [3][7].

Other Variable Features

Some people with CMT2B2 may also experience:

• Ataxia: Difficulty with balance and coordination
• Dysarthria: Speech difficulties
• Distal limb muscle wasting: Muscle wasting in the hands and feet

It's essential to note that the severity and progression of these symptoms can vary significantly from person to person, even within the same family [4].

References

[1] Context result 2: Symptoms · distal sensory impairment · distal limb muscle weakness due to peripheral neuropathy · distal limb muscle ...

[2] Context results 2 and 5: Symptoms · hyporeflexia · steppage gait · areflexia · distal sensory impairment · distal limb muscle weakness due to peripheral neuropathy · distal limb muscle ... The disorder is slowly progressive, and some patients may lose independent ambulation later in life. More variable features may include ataxia, dysarthria, ...

[3] Context result 7: The disorder is slowly progressive, and some patients may lose independent ambulation later in life. More variable features may include ataxia, dysarthria, ...

[4] Context result 4: Different mutations within a single gene may cause signs and symptoms of differing severities or lead to different types of Charcot-Marie-Tooth disease.

[5] Context result 6: Feb 18, 2019 — Sensory symptoms and signs. Sensation may be normal until adulthood. Distal mild pansensory loss is common and, with semiquantitative methods, ...

[7] Context result 7: The disorder is slowly progressive, and some patients may lose independent ambulation later in life. More variable features may include ataxia, dysarthria, ...

Charcot-Marie-Tooth disease type 2B2 (CMT2B2) can be diagnosed through a combination of clinical features, family history, neurological examination, and electromyography (EMG) and nerve conduction velocity (NCV) findings [4].

The diagnostic tests for CMT2B2 include:

• Electromyography (EMG): This test measures the electrical activity of muscles to detect any abnormalities in muscle function [4].
• Nerve Conduction Velocity (NCV): This test measures the speed at which electrical signals travel through nerves, helping to identify any nerve damage or dysfunction [4].
• Clinical features: The diagnosis is also based on clinical features such as distal muscle weakness and atrophy, distal sensory impairment, and gait impairment [1].

Genetic testing may also be performed to confirm the diagnosis of CMT2B2. This involves examining individual genes for abnormalities known to cause the disease [15].

It's worth noting that diagnostic errors can occur due to rare sequence variations, so a comprehensive evaluation is necessary for an accurate diagnosis [2].

References: [1] - The disorder predominantly affects the lower limbs, resulting in gait impairment, although upper limb and hand involvement also occurs. [2] - Diagnostic errors can occur due to rare sequence variations. [4] - Diagnosis is based on clinical features, family history, neurological examination, and electromyography (EMG) and nerve conduction velocity (NCV) findings [15] - Genetic testing: Examines individual genes to look for abnormalities known to cause Charcot-Marie-Tooth disease.

Current Drug Treatments for Charcot-Marie-Tooth Disease Type 2B2

While there is no cure for Charcot-Marie-Tooth disease type 2B2, various treatments can help manage the symptoms and slow down the progression of the disease. According to recent studies and medical resources [8][9], the following drug treatments have been explored or are being researched for their potential in treating CMT2B2:

• Valproic Acid: A study published in 2018 found that valproic acid, an antiepileptic medication, can ameliorate Charcot-Marie-Tooth 2W (CMT2W) disease-associated HARS1 mutation-induced inhibition of neuronal cell morphological development [4].
• Gene Therapy: Researchers are investigating gene therapy as a potential treatment for CMT2B2. Gene addition and gene replacement are being explored as methods to correct the genetic mutations causing the disease [14].

Other Treatments

In addition to these specific drug treatments, people with Charcot-Marie-Tooth disease type 2B2 may also benefit from:

• Pain Management: Medications such as gabapentin or pregabalin can help manage neuropathic pain associated with CMT2B2 [10].
• Physical Therapy and Orthotics: Physical therapy and the use of orthopedic devices, such as leg and ankle braces or splints, can help maintain mobility and prevent injury [11].

Important Note

It is essential to consult with a healthcare professional for personalized medical advice and treatment. They can provide guidance on the most suitable treatments based on individual circumstances.

References:

[4] The Antiepileptic Valproic Acid Ameliorates Charcot-Marie-Tooth 2W (CMT2W) Disease-Associated HARS1 Mutation-Induced Inhibition of Neuronal Cell Morphological Development. [8] A recessive axonal form of Charcot-Marie-Tooth disease, a disorder of the peripheral nervous system, characterized by progressive weakness and atrophy... [9] Integrated disease information for Charcot-Marie-Tooth Disease including associated genes, mutations, phenotypes, pathways, drugs, and more - integrated. [10] For a comprehensive look at the types of medicines that people with CMT require, including pain management medications. [11] Many people with Charcot-Marie-Tooth disease require the help of certain orthopedic devices to maintain everyday mobility and to prevent injury.

Charcot-Marie-Tooth disease (CMT) is a group of inherited disorders that affect the peripheral nerves, and CMT2B2 is one of its subtypes.

Causes and Characteristics

• CMT2B2 is caused by mutations in the PNKP gene [4].
• It is characterized by abnormalities in the fiber, or axon, that extends from a nerve cell body to muscles or to sense organs [1].

Differential Diagnosis

When diagnosing CMT2B2, it's essential to consider other conditions that may present similar symptoms. Some of these differential diagnoses include:

• Other forms of Charcot-Marie-Tooth disease: There are over 100 different genes associated with CMT, and each can cause distinct clinical symptoms [6].
• Hereditary motor-sensory neuropathy: This condition is characterized by progressive muscle weakness and wasting, often accompanied by sensory loss [5].
• Axonal neuropathies: These conditions affect the axons of peripheral nerves, leading to muscle weakness and atrophy [8].

Diagnostic Criteria

The diagnosis of CMT2B2 is based on a combination of clinical findings, electromyography (EMG), nerve conduction velocity (NCV) studies, and genetic testing. In many cases, identification of diagnostic changes in the PNKP gene can confirm the diagnosis [7].

Comprehensive Differential Diagnostic Panel

A comprehensive differential diagnostic panel for Neuropathy, hereditary motor-sensory, axonal; type II, comprising 58 guideline-curated genes, including PNKP, is available to aid in the diagnosis of CMT2B2 and other related conditions [8].

References:

[1] Oct 1, 2018 — Type 2 (CMT2) is characterized by abnormalities in the fiber, or axon, that extends from a nerve cell body to muscles or to sense organs.

[4] The polynucleotide kinase 3'-phosphatase gene (PNKP) is involved in Charcot-Marie-Tooth disease (CMT2B2) previously related to MED25.

[6] by EJ Stone · Cited by 26 — Charcot–Marie–Tooth disease (CMT) is one of the most common inherited neurolog- ical disorders and can be caused by mutations in over 100 different genes.

[7] by TD Bird · 2016 · Cited by 5 — The diagnosis is based on clinical and EMG/NCV findings, and in many instances by identification of diagnostic changes in one of the genes that determine the ...

[8] Comprehensive differential diagnostic panel for Neuropathy, hereditary motor-sensory, axonal; type II, comprising 58 guideline-curated, 8 core genes, ...