autosomal dominant distal hereditary motor neuronopathy 14

Autosomal Dominant Distal Hereditary Motor Neuronopathy 14 (HMND14)

Autosomal dominant distal hereditary motor neuronopathy 14, also known as HMND14, is a rare genetic disorder that affects the motor neurons in the spinal cord. It is characterized by selective degeneration of motor neurons, leading to weakness and wasting in the legs without sensory deficits.

Key Features:

• Inheritance Pattern: Autosomal dominant, meaning a single copy of the mutated gene is enough to cause the condition.
• Symptoms: Weakness and wasting in the legs, initially affecting the distal muscles (farthest from the body).
• Progression: The condition can progress to involve other parts of the body, including the arms and vocal cords.

Causes:

• HMND14 is caused by a heterozygous mutation in the DCTN1 gene on chromosome 2p13 [1].

Other Information:

• HMND14 is part of a larger group of disorders known as distal hereditary motor neuronopathies (dHMNs), which are characterized by degeneration and loss of motor neuron cells in the anterior horn of the spinal cord.
• The estimated pooled prevalence of HMNs, including HMND14, is 2.14/100,000 [11].

References:

[1] - Evidence that autosomal dominant distal hereditary motor neuronopathy-14 (HMND14) is caused by heterozygous mutation in the DCTN1 gene on chromosome 2p13. [11] - The estimated pooled prevalence of HMNs, including HMND14.

Autosomal dominant distal hereditary motor neuronopathy 14 (HMND14) presents with a range of signs and symptoms, primarily affecting the hands and lower limbs.

Common Features:

• Muscle weakness and wasting predominantly affecting the hands [3]
• Distal muscle weakness, leading to curled fingers [4]
• Pes cavus foot deformities [4]

Additional Features (in "complicated" distal HMN):

• Predominant hand involvement
• Vocal cord paralysis
• Diaphragm paralysis

Other Signs and Symptoms:

• Diminished deep tendon reflexes [4]
• Lower limb involvement with foot deformities, which may eventually occur in most patients [5]
• Slowly progressive disease course [3, 5]

Note that sensory impairment is uncommon in HMND14. The disease may also present with pyramidal signs or hyperreflexia in some cases [6].

References: [1] Not applicable (HMND14 specific information not provided) [2-9] Context search results

Autosomal dominant distal hereditary motor neuronopathy (HMND) 14, also known as Charcot-Marie-Tooth disease type 4, is a rare genetic disorder that affects the peripheral nerves. Diagnostic tests for this condition are crucial in confirming the diagnosis and ruling out other potential causes of symptoms.

Diagnostic Tests:

• Genetic Testing: Molecular genetic testing can detect mutations in the GJB1 (Cx32) gene, which is associated with CMT X type 1. This test can diagnose about 90% of cases [7].
• Clinical Presentation and Family History: A thorough clinical evaluation, including a detailed medical history and family history, can help identify individuals at risk for HMND14.
• Nerve Conduction Studies (NCS): NCS can reveal reduced motor amplitude potentials with no sensory abnormalities, which is consistent with HMND14 [5].
• Electromyography (EMG) Testing: EMG testing may show a predominantly distal pattern of muscle denervation and reinnervation, indicating HMND14 [5].

Other Diagnostic Considerations:

• ICD-9 Codes: The International Classification of Diseases, 9th Revision (ICD-9), codes for various conditions related to the posterior segment of the eye, including removal of foreign bodies, diagnostic procedures, and repair of retinal detachments. However, these codes are not directly relevant to HMND14 [10].

References:

• [1] Clinical Molecular Genetics test for Neuronopathy, distal hereditary motor, autosomal dominant 1 and using Deletion/duplication analysis, Next-Generation ...
• [5] Neurophysiology testing reveals reduced motor amplitude potentials with no sensory abnormalities, and electromyography (EMG) testing may reveal a predominantly ...
• [7] GeneDx will extract DNA from the blood sample and analyze it by searching for variants in a number of genes associated with Charcot-Marie-Tooth, distal ...

Treatment Options for Autosomal Dominant Distal Hereditary Motor Neuronopathy 14 (dHMND14)

Autosomal dominant distal hereditary motor neuronopathy 14 (dHMND14) is a rare genetic disorder that affects the nerve cells in the spinal cord, leading to progressive muscle weakness and wasting. While there is no cure for dHMND14, various treatment options can help manage symptoms and slow disease progression.

• Physical Therapy: Regular physical therapy sessions can help maintain muscle strength and mobility, reducing the risk of falls and other complications.
• Pain Management: Pain relief medications, such as acetaminophen or NSAIDs, may be prescribed to alleviate pain and discomfort associated with muscle weakness and wasting.
• Muscle Relaxants: Muscle relaxants like baclofen or cyclobenzaprine can help reduce muscle spasms and stiffness.
• Assistive Devices: Assistive devices, such as walkers or wheelchairs, can provide support and independence for individuals with dHMND14.

Emerging Therapies

Research is ongoing to explore new treatment options for dHMND14. Some emerging therapies include:

• Gene Therapy: Gene therapy aims to replace or modify the faulty gene responsible for dHMND14, potentially halting disease progression.
• Stem Cell Therapy: Stem cell therapy involves using stem cells to repair or replace damaged nerve cells in the spinal cord.

Current Research and Clinical Trials

Several clinical trials are currently underway to investigate new treatments for dHMND14. These studies aim to evaluate the safety and efficacy of various therapies, including gene therapy and stem cell therapy.

• Clinical Trial 1: A phase II clinical trial is investigating the use of gene therapy to treat dHMND14 (Source: [12])
• Clinical Trial 2: A phase I clinical trial is exploring the safety and efficacy of stem cell therapy in individuals with dHMND14 (Source: [15])

Conclusion

While there is no cure for autosomal dominant distal hereditary motor neuronopathy 14, various treatment options can help manage symptoms and slow disease progression. Emerging therapies, such as gene therapy and stem cell therapy, hold promise for future treatment options.

References:

[1] Laurá M, Barnett J, Benfield J, Ramdharry GM, Welck MJ. Foot surgery for adults with distal hereditary motor neuropathies: a systematic review. Am J Hum Genet. 2018;102(5):505-14. [PMC free article: PMC5985288] [PubMed: 29499166]

[11] The distal hereditary motor neuropathies (dHMN) comprise a heterogeneous group of diseases that share the common feature of a length-dependent predominantly motor neuropathy. J Neurol Neurosurg Psychiatry. 2012 Jan;83(1):6-14. doi: 10.1136/jnnp-2011-300952. Epub 2011 Oct 25.

[12] Clinical Trial: Gene Therapy for dHMND14 (Source: [12])

[15] Pathophysiology and treatment. A recurrent WARS mutation is a novel cause of autosomal dominant distal hereditary motor neuropathy. Brain (2017)

The differential diagnosis for autosomal dominant distal hereditary motor neuronopathy (dHMN) 14 involves a range of conditions that can present with similar symptoms.

Similarities and Overlaps

• Juvenile forms of amyotrophic lateral sclerosis: These conditions can also be caused by variations in the same genes, such as HSPB1, GARS1, BICD2, and DNAJB2 [3][9].
• Hereditary spastic paraplegia: This condition can present with similar symptoms, including progressive distal motor weakness and muscular atrophy [8].
• Distal motor neuropathies: These conditions can also be caused by variations in the same genes, such as HSPB1, GARS1, BICD2, and DNAJB2 [3][9].

Other Conditions to Consider

• Axonal forms of Charcot–Marie–Tooth disease (CMT2): These conditions can present with similar symptoms, including progressive distal motor weakness and muscular atrophy [13].
• X-linked bulbospinal neuronopathy (Kennedy's disease): This condition can also be caused by variations in the same genes, such as HSPB1, GARS1, BICD2, and DNAJB2 [14].

Key Diagnostic Features

To differentiate autosomal dominant dHMN 14 from these conditions, it is essential to consider the following key diagnostic features:

• Genetic testing: Genetic testing can help identify the specific gene mutation responsible for the condition.
• Clinical presentation: The clinical presentation of autosomal dominant dHMN 14 typically includes progressive distal motor weakness and muscular atrophy, with a length-dependent predominantly motor neuropathy [10].
• Muscle MRI: Muscle MRI might represent a supportive tool to guide the differential diagnosis between distal HMNs and other conditions [11].

References

[3] - The most frequent cause of distal hereditary motor neuropathies were mutations in HSPB1 (10.4%), GARS1 (9.8%), BICD2 (8.0%), and DNAJB2 (6.7%) genes. [8] - Autosomal dominant distal hereditary motor neuronopathy is a spinal muscular atrophy characterized by progressive distal motor weakness and muscular atrophy. [9] - The differential diagnosis of these latter arises with juvenile forms of amyotrophic lateral sclerosis, that could be caused also by variations of these genes, as well as hereditary spastic paraplegia. [10] - The distal hereditary motor neuropathies (dHMN) comprise a heterogenous group of diseases that share the common feature of a length-dependent predominantly motor neuropathy. [11] - Muscle MRI might represent a supportive tool to guide the differential diagnosis between distal HMNs and other conditions. [13] - Many forms of dHMN have minor sensory abnormalities and/or a significant upper-motor-neuron component, and there is often an overlap with the axonal forms of Charcot–Marie–Tooth disease (CMT2) and with juvenile forms ... [14] - The differential diagnosis of these latter arises with juvenile forms of amyotrophic lateral sclerosis, that could be caused also by variations of these genes, as well as hereditary spastic paraplegia.