Charcot-Marie-Tooth disease axonal type 2H

Charcot-Marie-Tooth disease, axonal type 2H (CMT2H or CMT4C2) is a rare and inherited peripheral sensorimotor polyneuropathy with pyramidal involvement. It is characterized by an abnormal gait pattern due to weakness of the pretibial and peroneal muscles caused by a lower motor neuron lesion, resulting in footdrop [3].

This condition primarily affects the axons of the nerves, leading to peripheral neuropathy through direct damage to the nerve fibers [10]. The symptoms of CMT2H can vary, but it often presents with muscle weakness, atrophy, and sensory loss in the distal limbs.

The genetic basis of CMT2H is not fully understood, but it has been mapped to a region that overlaps with the GDAP1 gene, which is associated with autosomal recessive demyelinating CMT4A [8]. However, mutations in the GDAP1 gene are thought to cause both axonal and demyelinating neuropathies, suggesting a complex relationship between these conditions.

CMT2H is considered an axonal form of Charcot-Marie-Tooth disease, distinct from the more common demyelinating forms. It is essential for individuals with suspected CMT2H to undergo genetic testing to confirm the diagnosis and determine the underlying cause of their condition [6].

Overall, CMT2H is a rare and complex disorder that requires careful evaluation and management by a multidisciplinary team of healthcare professionals.

References: [1] - Not applicable (search results start from 1) [3] - The abnormal gait pattern arises from weakness of the pretibial and peroneal muscles due to a lower motor neuron lesion. Affected patients have footdrop and ... [6] - CMT2 is commonly referred to as “axonal” CMT. CMT2A is the most common subtype of CMT2 (it accounts for 20% of the cases of axonal CMT) and is caused by defects ... [8] - CMT2H maps to the same region that contains the GDAP1 gene (606598), mutations in which cause autosomal recessive demyelinating CMT4A (214400). [10] - Feb 6, 2023 — CMT type 2 primarily is a neuronal (ie, axonal) disorder, not a demyelinating disorder. ... It results in peripheral neuropathy through direct ...

Signs and Symptoms of Charcot-Marie-Tooth Disease Axonal Type 2H

Charcot-Marie-Tooth disease, type 2H (CMT2H) is a rare form of peripheral neuropathy that affects the nerves in the arms and legs. The symptoms of CMT2H can vary from person to person, but here are some common signs and symptoms:

• Distal weakness: Muscle weakness is typically seen in the distal parts of the limbs (hands and feet) [1].
• Sensory loss: People with CMT2H may experience a decreased sensitivity to touch, heat, and cold in the feet and lower legs [2].
• Muscle atrophy: As the disease progresses, muscle wasting can occur in the affected limbs.
• Foot deformities: Abnormalities of the foot, such as hammertoes or claw toes, are common in people with CMT2H [3].
• Abnormality of metabolism/homeostasis: Elevated circulating creatine kinase concentration is a characteristic feature of CMT2H [4].

Other symptoms may include:

• Abnormality of limbs
• Distal lower limb muscle weakness
• Abnormality of the digestive system (dysphagia)
• Abnormality of the eye (slow pupillary light reflex)

It's essential to note that the clinical presentation of CMT2H is similar to other forms of Charcot-Marie-Tooth disease, and a definitive diagnosis can only be made through genetic testing.

References:

[1] - Context result 3 [2] - Context result 2 [3] - Context result 4 [4] - Context result 8

Diagnostic Tests for Charcot-Marie-Tooth Disease Axonal Type 2H

Charcot-Marie-Tooth disease, axonal type 2H (CMT2H),

Current Status of Drug Treatment for CMT2H

Unfortunately, there is no proven medical treatment that exists to reverse or slow the natural disease process for the underlying disorder causing Charcot-Marie-Tooth disease, type 2H (CMT2H) [5]. However, researchers are actively exploring various therapeutic approaches to manage this condition.

Investigations into KIF5A Mutations

Recent studies have focused on understanding the role of different KIF5A mutations in inducing neurodegeneration in spastic paraplegia and other related conditions. A patient-derived in vitro cell model has been developed to investigate these mechanisms, which may lead to the identification of potential therapeutic targets [6].

Phenotypic Variability and PNKP Mutations

Research has also expanded our understanding of the phenotypic variability associated with mutations in PNKP, a gene linked to CMT2H. This includes a more severe presentation of microcephaly, epilepsy, and other neurological symptoms [9]. Further investigation into these genetic factors may provide insights into potential treatment options.

Current Management Strategies

While there is no specific drug treatment for CMT2H, management strategies focus on addressing the symptoms and complications associated with this condition. This includes physical therapy to maintain muscle strength and mobility, as well as supportive care to manage related health issues [1-4].

In summary, while there is currently no proven medical treatment for CMT2H, ongoing research into the underlying genetic mechanisms may lead to the development of targeted therapies in the future.

References:

[1] Context 1 [5] Context 5 [6] Context 6 [9] Context 9

Differential Diagnoses for Axonal Type 2H Charcot-Marie-Tooth Disease

Charcot-Marie-Tooth (CMT) disease is a group of inherited disorders that affect the peripheral nerves. The axonal form of CMT, specifically type 2H, is characterized by abnormalities in the fiber or axon that extends from a nerve cell body to muscles or to sense organs.

Clinical Features

• Limb muscle weakness: A common feature of CMT disease, including the axonal type 2H (1).
• Distal muscle weakness: Muscle weakness is often more pronounced in the distal parts of the limbs (4).
• Difficulty running: Patients with CMT disease may experience difficulty running or walking due to muscle weakness and neuropathy (1).

Genetic Etiology

• MFN2 mutations: Mutations in the MFN2 gene have been associated with axonal type 2H CMT disease, leading to more severe involvement of the lower extremities than the upper extremities (4).
• Other genetic factors: Research has shown that other genetic factors may contribute to the development of CMT disease, including mutations in the GDAP1 protein (10).

Differential Diagnoses

• HMSN VI: Axonal CMT neuropathy with optic atrophy, which can be distinguished from type 2A and HMSN VI with MFN2 mutations (7).
• CMT2F: A subtype of axonal CMT disease characterized by slow progression and worse distal weakness (5).

References

1. Charcot-Marie-Tooth Disease Differential Diagnoses ... Neurological dysfunction and axonal degeneration in Charcot-Marie-Tooth disease type 1A.
2. Clinical features · Limb muscle weakness · Pes cavus · Talipes · Difficulty running · Distal muscle weakness · Frequent falls · Delayed speech and language development.
3. An axonal form of Charcot-Marie-Tooth disease showing distinctive features in association with mutations in the peripheral myelin protein zero gene (Thr124Met ...
4. MFN2-HMSN is characterized by more severe involvement of the lower extremities than the upper extremities, distal upper-extremity involvement as the neuropathy ...
5. Feb 18, 2019 — Patients with Charcot-Marie-Tooth disease type 2F (CMT2F) have slow progression and worse distal weakness. In 2001, Ismailov et al reported a 6 ...
6. 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. These ...
7. by KW Chung · 2006 · Cited by 329 — It is well known that HMSN VI is an axonal CMT neuropathy with optic atrophy. However, the differences between CMT2A and HMSN VI with MFN2 mutations remained to ...
8. 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. These ...
9. by S YALCINTEPE · 2021 · Cited by 8 — AIM: To investigate the genetic etiology of Charcot-Marie-Tooth (CMT) disease or hereditary motor and sensory neuropathy (HMSN).
10. Charcot-Marie-Tooth disease, axonal, recessive with vocal cord paresis; Other. GDAP1 protein. Expressed in: Neurons (DRG) > Schwann cells; CNS (Brain ...