Charcot-Marie-Tooth disease X-linked recessive 5

Charcot-Marie-Tooth Disease X-linked Recessive 5 (CMTX5)

Charcot-Marie-Tooth disease X-linked recessive 5, also known as CMTX5, is a rare genetic disorder that affects the peripheral nerves. It is characterized by an X-linked recessive inheritance pattern, meaning it primarily affects males.

Clinical Features:

• Optic Atrophy: A degeneration of the optic nerve leading to vision loss.
• Deafness: Hearing impairment or complete deafness.
• Polyneuropathy: A condition affecting multiple peripheral nerves, causing muscle weakness and atrophy.

Additional Symptoms:

• Some patients may experience additional symptoms such as:
  • Muscle weakness
  • Atrophy (wasting) of muscles
  • Sensory loss in the hands and feet

Causes:

CMTX5 is caused by mutations in the PRPS1 gene, which codes for an enzyme involved in purine metabolism.

References:

• [2] X-linked Charcot-Marie-Tooth disease type 5 is a rare, genetic, peripheral sensorimotor neuropathy characterized by an X-linked recessive inheritance.
• [5] CMTX5, an X-linked recessive disorder with deafness and optic neuropathy caused by alterations in the PRPS1 gene.
• [8] The phenotype of X-linked Charcot-Marie-Tooth disease-5 typically comprises the triad of optic atrophy, deafness, and polyneuropathy.

Symptoms of CMTX5

Charcot-Marie-Tooth disease type X-linked recessive 5 (CMTX5) is a rare genetic disorder that affects the peripheral nerves. The symptoms of CMTX5 can vary in severity and may include:

• Muscle weakness and atrophy: Individuals with CMTX5 experience muscle weakness and reduction in size, particularly in the lower legs and feet [1].
• Decreased sensation: People with CMTX5 typically have a decreased sensitivity to touch, heat, and cold in the feet and lower legs [3].
• Optic atrophy: The phenotype of CMTX5 often includes optic atrophy, which is a degeneration of the optic nerve leading to vision problems [8].
• Deafness: Some individuals with CMTX5 may experience hearing loss or deafness [8].
• Polyneuropathy: CMTX5 can cause polyneuropathy, which is a condition characterized by damage to multiple peripheral nerves [8].

Additional symptoms

In females, who are less likely to be affected by CMTX5 due to its X-linked recessive inheritance pattern, the symptoms may be milder and include:

• Pes cavus: A foot deformity where the arch of the foot is higher than normal [6].
• Slight hand muscle atrophy: Some individuals with CMTX5 may experience slight muscle wasting in the hands [6].
• Tremor: Females with CMTX5 may also experience tremors, particularly in childhood or adulthood [6].

It's essential to note that the symptoms of CMTX5 can vary widely among affected individuals and may not be present in all cases.

References: [1] - Context result 1 [3] - Context result 3 [6] - Context result 6 [8] - Context result 8

Diagnostic Tests for Charcot-Marie-Tooth Disease X-linked Recessive 5

Charcot-Marie-Tooth disease X-linked recessive 5 (CMTX5) is a rare genetic disorder that affects the peripheral nerves. Diagnosing CMTX5 can be challenging, but several diagnostic tests are available to confirm the condition.

• Nerve Conduction Studies (NCS): NCS measure the speed and strength of electrical signals traveling through the nerves. In males with CMTX5, nerve conduction velocities in the upper limb motor nerves are usually decreased, typically in the intermediate range of 30-45 m/s [13].
• DNA Testing: Genetic testing can detect mutations in the GJB1 (Cx32) gene, which is responsible for CMTX5. According to a study published on February 6, 2023, about 90% of cases of CMT X can be detected by means of molecular genetic testing of the GJB1 gene [6].
• Clinical Examination: A thorough clinical examination, including a review of family and personal history, is essential for diagnosing CMTX5. The condition is characterized by progressive distal muscle weakness and atrophy, particularly in the lower extremities.
• Genetic Testing Algorithms: Current genetic test algorithms for Charcot Marie Tooth (CMT) disease are based on family details and comprehensive clinical and neurophysiological data gathered under ideal conditions [10]. However, these algorithms may not always be applicable in a diagnostic laboratory setting.

It's essential to note that genetic testing is not needed to diagnose CMTX5, as the condition can often be identified through a combination of clinical examination, NCS, and family history [5].

References:

[1] Clinical Genetic Test offered by Labcorp Genetics (formerly Invitae) for conditions (123): Mitochondrial complex IV deficiency, nuclear type 1; [2] Apr 30, 2024 — GENETIC TESTING IS NOT NEEDED TO DIAGNOSE CMT. [3] Feb 6, 2023 — About 90% of cases of CMT X can be detected by means of molecular genetic testing of the GJB1 gene. [4] Diagnosis is based on family and personal history, clinical examination, nerve conduction studies (NCS), and DNA testing (for CMTX1). [5] These tests, which can detect the most common genetic defects known to cause Charcot-Marie-Tooth disease, are done with a blood sample.

Current Status of Drug Treatment for Charcot-Marie-Tooth Disease (CMT) X-linked Recessive

Unfortunately, there is still no effective drug treatment available for the X-linked recessive form of Charcot-Marie-Tooth disease (CMT). The current management relies on rehabilitation therapy and surgical treatment of skeletal deformities. This is because the underlying genetic cause of the disease has not been effectively targeted by any existing medication.

• Rehabilitation Therapy: Physical therapy, occupational therapy, and speech therapy are often used to manage symptoms such as muscle weakness, atrophy, and sensory loss.
• Surgical Treatment: Surgery may be necessary to correct skeletal deformities, such as foot or ankle problems, that can occur in people with CMT.

It's worth noting that researchers are actively exploring gene-based therapeutic approaches, including gene therapy, which aim to address the underlying genetic cause of the disease. However, these treatments are still in the experimental stages and not yet available for widespread use [5].

References:

[5] by S Beloribi-Djefaflia · 2023 · Cited by 14 — Currently, there is no drug capable of counteracting the disease, so patients' management is based on rehabilitation and occupational therapy with psychological support.

The differential diagnosis for Charcot-Marie-Tooth disease (CMT) X-linked recessive includes other CMT forms and chronic inflammatory demyelinating polyneuropathy, particularly for CMTX1 [3]. This is because the symptoms of CMT can be similar to those of other neurological conditions.

Some of the key factors that need to be considered in the differential diagnosis of CMT X-linked recessive include:

• A positive family history, which can make CMT more likely
• A pedigree that shows a pattern of inheritance consistent with an X-linked recessive disorder [7]
• The presence of other symptoms such as muscle weakness or atrophy, sensory loss, and autonomic dysfunction

It's also worth noting that the differential diagnosis for CMT is wide, and a thorough evaluation by a neurologist or geneticist is often necessary to determine the underlying cause of the condition.

In terms of specific conditions that may be considered in the differential diagnosis of CMT X-linked recessive, these can include:

• Other forms of hereditary motor and sensory neuropathy
• Leukodystrophies (autosomal recessive or X-linked recessive)
• Chronic inflammatory demyelinating polyneuropathy

It's also worth noting that while the majority of mutations associated with CMT are autosomal dominant, CMT also displays X-linked and recessive inheritance [9]. This means that a genetic evaluation may be necessary to determine the underlying cause of the condition.