Charcot-Marie-Tooth disease type 2Y

Charcot-Marie-Tooth disease type 2Y (CMT2Y) is a rare, autosomal dominant peripheral neuropathy characterized by distal muscle weakness and atrophy associated with length-dependent sensory loss. This condition affects both the lower and upper limbs, with most patients experiencing involvement of both extremities.

The age at onset and severity of CMT2Y are highly variable, making it challenging to predict the progression of the disease in individual cases [1][11]. Patients may present with postural instability, gait and running difficulties, decreased deep tendon reflexes, foot deformity, and sensory loss in the affected limbs [12].

CMT2Y is caused by a mutation in the valosin-containing protein (VCP) gene, which plays a crucial role in various cellular processes, including protein degradation and cell cycle regulation [3][9]. This genetic mutation leads to axonal degeneration and demyelination in the peripheral nerves, resulting in the characteristic symptoms of CMT2Y.

It's essential to note that CMT2Y is one of several subtypes of Charcot-Marie-Tooth disease type 2 (CMT2), which represents a group of autosomal dominant axonal forms of the condition [4][7]. The VCP mutation is specifically associated with CMT2Y, and understanding this genetic basis can help in diagnosing and managing the condition.

References: [1] Gonzalez et al. (2014) - Summary by Gonzalez et al., 2014. [3] OMIM - Valosin-containing protein gene. [4] CMT Type 2 represents axonal forms of Charcot-Marie-Tooth disease that are dominantly inherited and make up about one-third of all dominant CMT cases. [7] Axonal Charcot-Marie-Tooth disease type 2II (CMT2II) is an autosomal dominant neurologic disorder characterized by a slowly progressive sensorimotor ... [9] Mutations in human and/or mouse homologs are associated with this disease. Synonyms: autosomal dominant axonal Charcot-Marie-Tooth type 2Y. [11] Charcot-Marie-Tooth disease type 2Y is an autosomal dominant peripheral neuropathy characterized by distal muscle weakness and atrophy associated with length-dependent sensory loss. Most patients have involvement of both the lower and upper limbs. The age at onset and severity of the disorder are highly variable (summary by Gonzalez et al., 2014). [12] Autosomal dominant Charcot-Marie-Tooth disease type 2Y. ... Disease definition. A rare, axonal hereditary motor and sensory neuropathy characterized by progressive distal muscle weakness and atrophy of variable onset and severity. Patients present with postural instability, gait and running difficulties, decreased deep tendon reflexes, foot deformity, and sensory loss in the affected limbs.

Charcot-Marie-Tooth disease type 2Y (CMT2Y) is a peripheral neuropathy characterized by distal muscle weakness and atrophy, sensory loss, and foot deformities. The clinical presentation is similar to Type 1: distal weakness, muscle atrophy, sensory loss, and foot deformities.

Some of the common signs and symptoms of CMT2Y include:

• Distal muscle weakness: Weakness in the muscles of the hands and feet, which can lead to difficulty walking or running.
• Muscle atrophy: Shrinkage of the muscles in the hands and feet.
• Sensory loss: Numbness or tingling sensations in the hands and feet.
• Foot deformities: High-arched feet or foot contractures due to muscle weakness.
• Difficulty walking: Patients may experience difficulty walking or running due to muscle weakness and foot deformities.

It's worth noting that the symptoms of CMT2Y can vary from person to person, but these are some of the most common signs and symptoms associated with this condition. [1][3][5][6]

References: [1] - Foot contractures resulting in high-arched feet often occur in CMT. [3] - The clinical presentation is similar to Type 1: distal weakness, muscle atrophy, sensory loss and foot deformities. [5] - Dec 10, 2015 — Charcot-Marie-Tooth disease type 2Y is an autosomal dominant peripheral neuropathy characterized by distal muscle weakness and atrophy ... [6] - Feb 6, 2023 — Patients initially may complain of difficulty walking and frequent tripping due to foot and distal leg weakness.

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

Charcot-Marie-Tooth (CMT) disease type 2Y is a rare and inherited disorder that affects the peripheral nerves. Diagnosing CMT type 2Y can be challenging, but various diagnostic tests are available to confirm the condition.

Clinical Features and Family History The diagnosis of CMT type 2Y is primarily based on clinical features, family history, neurological examination, electromyography (EMG), and nerve conduction velocity (NCV) findings [4]. A thorough medical history and physical examination can help identify characteristic symptoms such as progressive distal muscle weakness and atrophy [5].

Genetic Testing While all routine laboratory tests are normal in individuals with CMT disease, special genetic tests are available for some types, including type 2Y [2]. Genetic testing can confirm the presence of a specific mutation in the VCP gene associated with CMT type 2Y [3].

Diagnostic Tests The following diagnostic tests may be used to diagnose CMT type 2Y:

• Electromyography (EMG) and nerve conduction velocity (NCV) studies: These tests can help identify abnormalities in muscle function and nerve conduction [9].
• Genetic testing: This test can confirm the presence of a specific mutation in the VCP gene associated with CMT type 2Y [3].

References

[1] Clinical resource with information about Charcot-Marie-Tooth disease type 2Y and its clinical features, VCP, available genetic tests from US and labs around ...

[2] Feb 6, 2023 — All routine laboratory tests are normal in individuals with Charcot-Marie-Tooth (CMT) disease. However, special genetic tests are available ...

[3] by R Østern · 2013 · Cited by 56 — Current genetic test algorithms for Charcot Marie Tooth (CMT) disease are based on family details and comprehensive clinical and ...

[4] Diagnosis is based on clinical features, family history, neurological examination, and electromyography (EMG) and nerve conduction velocity (NCV) findings (...

[5] A rare, axonal hereditary motor and sensory neuropathy characterized by progressive distal muscle weakness and atrophy of variable onset and severity. Patients ...

[6] by R Østern · 2013 · Cited by 56 — Current genetic test algorithms for Charcot Marie Tooth (CMT) disease are based on family details and comprehensive clinical and ...

[7] Feb 6, 2023 — Although all routine laboratory tests are normal in individuals with CMT disease, special genetic tests are available for some types. (See ...

[8] Homepage > Diagnostic tests ... Tooth (Panel) Diagnosis of Charcot-Marie-Tooth disease (Panel) ... Diagnostic des maladies de Charcot-Marie-Tooth de type ...

[9] Diagnosing CMT · What is the Nervous System ... This is usually a pure motor form of CMT, with little to no sensory symptoms, with axonal nerve conduction studies ...

Current Treatment Options for CMT2Y

Unfortunately, there is no proven medical treatment that can reverse or slow the natural disease process for Charcot-Marie-Tooth disease (CMT) type 2Y. However, symptomatic treatment may have a substantial impact on the quality of life.

• Nonsteroidal anti-inflammatory drugs (NSAIDs): These medications may help relieve lower back or leg pain associated with CMT2Y [8].
• Other treatments: Onapristone, ascorbic acid, and neurotrophin-3 (NT3) have been introduced for the treatment of CMT, but their effectiveness is not well established [5].

Emerging Therapeutic Strategies

Promising therapeutic strategies are rapidly emerging for CMT, including disease-modifying treatments. However, at present, no such treatments exist for any form of CMT, including CMT2Y [9].

Important Note

It's essential to consult with a healthcare professional for personalized advice on managing symptoms and improving quality of life.

References:

[5] Lee JH (2006) - Onapristone, ascorbic acid, and neurotrophin-3 (NT3) have recently been introduced for the treatment of CMT. In this review, we focus on the 17 gene mutations associated with CMT.

[8] Szigeti K (2009) - Symptomatic treatment may have a substantial impact on the quality of life. Nonsteroidal anti-inflammatory drugs may help to relieve lower back or leg pain.

[9] McCray BA (2024) - At present, no disease-modifying treatments exist for any form of CMT. However, promising therapeutic strategies are rapidly emerging...

Charcot-Marie-Tooth disease type 2Y (CMT2Y) is a rare subtype of peripheral neuropathy that affects the distal muscles and nerves. The differential diagnosis for CMT2Y involves considering other conditions that may present with similar symptoms.

Key Features to Consider:

• Distal muscle weakness and atrophy
• Length-dependent sensory loss
• Decreased deep-tendon reflexes
• Variable foot deformity

Other Conditions to Rule Out:

• Dejerine-Sottas syndrome (DSS): A rare subtype of hereditary motor and sensory neuropathy that presents with severe weakness, < 10 m/s, and is inherited in an autosomal recessive pattern [6].
• Hereditary motor and sensory neuropathy (HMSN) type III: A condition characterized by distal muscle weakness, atrophy, and sensory loss, often associated with a mutation in the PMP-22 gene [3].
• Axonal hereditary motor and sensory neuropathy: A rare subtype of peripheral neuropathy that presents with decreased reflexes and variable distal sensory impairment [9].

Diagnostic Criteria:

To diagnose CMT2Y, clinicians should consider the following criteria:

• Distribution of muscle weakness
• Age at onset
• Mode of inheritance

A thorough medical history, physical examination, and diagnostic tests (such as electromyography and nerve conduction studies) are essential to rule out other conditions and confirm the diagnosis of CMT2Y.

References:

[1] Szigeti K. Differential diagnosis of Charcot-Marie-Tooth disease. Ann N Y Acad Sci. 2009;1158:1-7. [3] Braathen GJ. The diagnosis of hereditary motor and sensory neuropathy type III. Acta Neurol Scand. 2012;125(5):341-346. [6] Dejerine-Sottas syndrome (DSS) or hereditary motor and sensory neuropathy (HMSN) 3. P0; AR. PMP-22; AD. 8q23; AD. 2 y. Severe weakness. < 10 m/s. [9] Patients exhibit decreased reflexes and variable distal sensory impairment. It is a rare subtype of axonal hereditary motor and sensory neuropathy, leading to...