autosomal dominant distal hereditary motor neuronopathy

Autosomal dominant distal hereditary motor neuronopathy (dHMN) refers to a group of rare genetic disorders that primarily affect the motor neurons responsible for controlling muscle movement.

• Progressive muscle weakness and wasting: The disease is characterized by progressive muscle weakness and wasting, particularly affecting the distal muscles of the legs. This can lead to difficulties in walking and maintaining balance [1].
• Distal lower limb involvement: Weakness usually begins in the calf muscles and later involves more proximal muscles, affecting both the upper and lower limbs [3][13].
• Juvenile onset: The disease typically starts with symptoms appearing between the second and fourth decades of life, although it can occur earlier or later depending on the specific subtype [12][14].
• Genetic heterogeneity: Autosomal dominant dHMN is a genetically heterogeneous disorder, meaning that different genetic mutations can cause the same condition. Multiple genes have been identified as contributing to this disease, including autosomal dominant, recessive, and X-linked patterns of inheritance [15].

It's essential to note that each subtype of autosomal dominant distal hereditary motor neuronopathy has distinct characteristics, and a comprehensive diagnosis requires a thorough medical evaluation.

References: [1] - Context result 9 [3] - Context result 7 [12] - Context result 12 [13] - Context result 13 [14] - Context result 14 [15] - Context result 15

Autosomal dominant distal hereditary motor neuronopathy, also known as distal hereditary motor neuropathy type II, is a rare genetic disorder that affects the peripheral nervous system. The condition is characterized by progressive degeneration of motor neurons in the spinal cord, leading to muscle weakness and atrophy primarily in the distal limbs.

Common signs and symptoms:

• Muscle weakness and wasting in the hands, particularly affecting specific muscles [3]
• Foot deformity is a common feature, with curled fingers and pes cavus foot deformities [9]
• Diminished deep tendon reflexes
• Muscle spasm
• Lower limb amyotrophy
• Proximal muscle weakness

Additional features:

• Vocal cord paralysis due to involvement of the tenth cranial nerve [6]
• Hand tremor, scoliosis, hearing loss, scapular winging, brisk reflexes, and elevated CK levels in some patients [10]

Progression:

• Symptoms typically start in adolescence
• Muscle weakness and wasting progress over time, affecting primarily the distal limbs

It's essential to note that the severity and age of onset can vary widely among individuals with autosomal dominant distal hereditary motor neuronopathy. The condition is inherited in an autosomal dominant pattern, meaning one copy of the mutated gene is sufficient to cause the disorder.

References:

[3] Clinical features · Difficulty running · EMG: chronic denervation signs · Lower limb amyotrophy · Muscle spasm · Proximal muscle weakness · Spinal muscular atrophy ...

[6] There is significant muscle atrophy of the hands and lower limbs. The disorder is associated with vocal cord paresis due to involvement of the tenth cranial nerve.

[9] Signs include distal muscle weakness with curled fingers, pes cavus foot deformities (Fig. 180.1D), and diminished deep tendon reflexes.

[10] A variety of associated signs and symptoms have been reported in some patients, including hand tremor, scoliosis, hearing loss, scapular winging, brisk reflexes, and elevated CK levels.

Diagnostic Tests for Autosomal Dominant Distal Hereditary Motor Neuronopathy

Autosomal dominant distal hereditary motor neuronopathy (HMND) is a rare genetic disorder that affects the nerve cells in the spinal cord, leading to progressive muscle weakness and wasting. Diagnostic tests play a crucial role in confirming the diagnosis of HMND.

Clinical Molecular Genetics Test A clinical molecular genetics test for Neuronopathy, distal hereditary motor, autosomal dominant 1 can be performed using Deletion/duplication analysis, Next-Generation Sequencing (NGS) [1]. This test helps identify genetic mutations associated with HMND.

Genetic Testing In addition to clinical presentation and family history, genetic testing can be used to diagnose specific inherited peripheral neuropathies, including HMND [4]. Genetic tests such as Exome Sequencing with CNV Detection [6] can help identify genetic variants associated with the condition.

Neurophysiology Testing Neurophysiology testing reveals reduced motor amplitude potentials with no sensory abnormalities. Electromyography (EMG) testing may reveal a predominantly distal pattern of muscle involvement, indicating HMND [5].

Other Diagnostic Tests Other diagnostic tests that may be used to confirm the diagnosis of HMND include nerve conduction studies and electromyography (EMG) testing.

References:

• [1] Clinical Molecular Genetics test for Neuronopathy, distal hereditary motor, autosomal dominant 1
• [4] In addition to clinical presentation, nerve conduction studies, and family history, genetic testing can be used to diagnose specific inherited peripheral neuropathies
• [5] Neurophysiology testing reveals reduced motor amplitude potentials with no sensory abnormalities
• [6] Test Method: Exome Sequencing with CNV Detection. New York State Approved Test. PANEL AVAILABLE VIA PGnome Sequencing

Autosomal dominant distal hereditary motor neuronopathy (dHMN) is a rare genetic disorder characterized by degeneration and loss of motor neuron cells in the anterior horn of the spinal cord, leading to muscle atrophy. While there is no cure for dHMN, various treatment options are available to manage symptoms and slow disease progression.

Current Treatment Options:

• Physical Therapy: Regular physical therapy can help maintain muscle strength and mobility, reducing the risk of falls and other complications.
• Pain Management: Pain management strategies, such as medication or alternative therapies like acupuncture, can help alleviate pain associated with muscle atrophy.
• Muscle Relaxants: Muscle relaxants may be prescribed to reduce muscle spasms and discomfort.
• Assistive Devices: Assistive devices, such as walkers or wheelchairs, can help individuals with dHMN maintain independence and mobility.

Emerging Treatment Options:

• Gene Therapy: Researchers are exploring gene therapy as a potential treatment for dHMN. Gene therapy involves replacing or modifying the faulty gene responsible for the disease.
• Stem Cell Therapy: Stem cell therapy is another area of research, where stem cells are used to replace damaged motor neurons and promote muscle regeneration.

Specific Treatment for Autosomal Dominant Distal Hereditary Motor Neuronopathy:

While there is no specific treatment mentioned in the search results for autosomal dominant distal hereditary motor neuronopathy, researchers have identified a recurrent WARS mutation as a novel cause of this disorder [13]. Further research is needed to develop targeted treatments for this specific subtype.

References:

• [14] Distal hereditary motor neuronopathies (distal HMN, dHMN), sometimes also called distal hereditary motor neuropathies, are a genetically and clinically heterogeneous group of motor neuron diseases that result from genetic mutations in various genes and are characterized by degeneration and loss of motor neuron cells in the anterior horn of the spinal cord and subsequent muscle atrophy.
• [15] Hereditary sensory neuropathy type 1 (HSN1) is the most common subtype with an autosomal dominant pattern of inheritance, caused by several ...

The differential diagnosis for autosomal dominant distal hereditary motor neuronopathy (dHMN) includes several conditions that can present with similar clinical features.

• Juvenile forms of amyotrophic lateral sclerosis (ALS): These are slowly progressive neuromuscular disorders that primarily affect motor function, and can be caused by variations in the same genes responsible for dHMN [1][2].
• Hereditary spastic paraplegia: This is a group of rare genetic disorders characterized by progressive weakness and stiffness of the legs, which can also present with similar clinical features to dHMN [1][2].
• Other neuromuscular disorders: Such as juvenile forms of ALS, hereditary spastic paraplegia, and other motor neuron diseases that result from genetic mutations in various genes [3].

It's worth noting that the differential diagnosis for dHMN can be complex, and a comprehensive evaluation including clinical features, neurophysiologic testing, muscle MRI, muscle biopsy, and western blot of BAG3 protein in skeletal muscle may be necessary to accurately diagnose the condition [4].

References:

[1] Context 2 [2] Context 10 [3] Context 9 [4] Context 14