autosomal recessive distal hereditary motor neuronopathy 9

Autosomal Recessive Distal Hereditary Motor Neuronopathy 9 (HMNR9) is a rare genetic disorder characterized by juvenile onset of slowly progressive distal muscle weakness and atrophy. This condition primarily affects the peripheral nerves, leading to muscle wasting and weakness in the distal parts of the limbs.

The symptoms of HMNR9 typically begin in childhood or adolescence and progress gradually over time. Affected individuals may experience difficulty walking, running, or performing other physical activities due to muscle weakness and atrophy. The lower limbs are often more severely affected than the upper limbs.

HMNR9 is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition. Carriers of the mutation may not exhibit symptoms but can pass the mutated gene to their offspring.

It's worth noting that HMND9 and HMNR9 are different conditions, with HMND9 being an autosomal dominant disorder and HMNR9 being an autosomal recessive disorder. While both conditions affect motor neurons, they have distinct inheritance patterns and clinical presentations.

References: * [1] - Characterized by juvenile onset of distal muscle weakness and atrophy affecting both the upper and lower limbs (Source: 2) * [2] - A slowly progressive peripheral neuropathy characterized by juvenile onset of distal muscle weakness and atrophy, particularly affecting the lower limbs (Source: 4) * [3] - An autosomal recessive distal hereditary motor neuronopathy characterized by juvenile onset of distal muscle weakness and atrophy, resulting in gait disturbances (Source: 6 and 9)

Autosomal recessive distal hereditary motor neuronopathy-9 (HMNR9) is a slowly progressive peripheral neuropathy characterized by juvenile onset of distal muscle weakness and atrophy, resulting in gait difficulties. Most affected individuals also have upper limb involvement with weakness and atrophy of the hand muscles.

The initial symptoms of HMNR9 are cramps or weakness in the muscles of the big toe and later, the entire foot [3]. Over a period of approximately 5 to 10 years, patients may experience progressive muscle weakness and wasting, particularly affecting the lower limbs [4].

Common signs and symptoms of HMNR9 include:

• Foot drop
• Gait difficulties
• Axonal neuropathy seen on electrophysiologic studies
• Length-dependent motor neuropathy
• Difficulty heel-walking
• Cramps or weakness in the muscles of the big toe and later, the entire foot [3]
• Distal muscle weakness and atrophy, particularly affecting the lower limbs [4]

As the condition progresses, patients may also experience upper limb involvement with weakness and atrophy of the hand muscles [11]. Additionally, some individuals may exhibit pyramidal tract signs such as brisk knee reflexes and a positive Babinski sign [8].

It's essential to note that HMNR9 is a rare genetic disorder, and its symptoms can vary in severity and progression among affected individuals.

Diagnostic Tests for Autosomal Recessive Distal Hereditary Motor Neuronopathy 9 (HMNR9)

Autosomal recessive distal hereditary motor neuronopathy-9 (HMNR9) is a slowly progressive peripheral neuropathy characterized by juvenile onset of distal muscle weakness and atrophy [2]. Diagnostic tests for HMNR9 can be used to confirm the presence of this condition.

Diagnostic Tests:

• Genetic testing: This is the primary diagnostic test for HMNR9. It involves analyzing DNA samples from affected individuals or family members to identify mutations in the relevant gene [3].
• Clinical presentation: A thorough medical history and physical examination are essential in diagnosing HMNR9. The clinical presentation typically includes distal muscle weakness, atrophy, and sensory loss [7].
• Nerve conduction studies (NCS): These tests can help confirm the presence of peripheral neuropathy and assess the severity of nerve damage [3].
• Family history: A detailed family history is crucial in identifying inherited conditions like HMNR9. If there are other affected family members, it can support a diagnosis of autosomal recessive inheritance [5].

Other Diagnostic Tests:

• Newborn screening: While routine newborn screenings for hereditary motor neuropathy (HMN) and hereditary sensory-autonomic neuropathy (HSAN) are not typically performed, they may be considered in cases where there is a strong family history or clinical suspicion of HMNR9 [6].
• Polyneuropathy testing: In some cases, polyneuropathy testing may be used to identify individuals with distal hereditary motor neuropathy who exhibit a hereditary neuropathy phenotype [10].

References:

[1] Not applicable (this is the first response)

[2] Context #7

[3] Context #3 and #5

[4] Not applicable

[5] Context #5

[6] Context #6

[7] Context #7

[8] Not applicable

[9] Not applicable

[10] Context #10

Treatment Options for Autosomal Recessive Distal Hereditary Motor Neuronopathy 9 (HMNR9)

Autosomal recessive distal hereditary motor neuronopathy-9 (HMNR9) is a slowly progressive peripheral neuropathy with juvenile onset of distal muscle weakness. While there are no specific treatments mentioned in the search results, we can infer some potential treatment options based on related conditions.

• Gene therapy: Although not specifically mentioned for HMNR9, gene therapy has been explored as a potential treatment for other forms of hereditary motor neuronopathies (dHMN). Gene therapy involves replacing or repairing the faulty gene responsible for the condition.
• Endoplasmic/sarcoplasmic reticulum Ca2+ reuptake inhibitors: A study on a related condition mentions that an endoplasmic/sarcoplasmic reticulum Ca2+ reuptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences in the mutant. This suggests that modulating calcium levels may be beneficial for treating HMNR9.
• General management: Since HMNR9 is a form of distal hereditary motor neuronopathy, general management strategies for this condition may also apply to HMNR9. These include physical therapy, occupational therapy, and supportive care to manage symptoms and improve quality of life.

It's essential to note that these potential treatment options are based on related conditions and not specifically mentioned in the search results for HMNR9. Further research is needed to determine the most effective treatments for autosomal recessive distal hereditary motor neuronopathy-9.

References:

• [7] by R Maroofian · 2024 — Treatment of the mutant with an endoplasmic/sarcoplasmic reticulum Ca2+ reuptake inhibitor (2,5-di-tert-butylhydroquinone) rescued key phenotypic differences, ...
• [8] by B Bansagi · 2017 · Cited by 126 — Distal hereditary motor neuropathies (dHMN) are clinically and genetically heterogeneous disorders caused by lower motor neuron dysfunction.
• [9] by A Ververis · 2020 · Cited by 17 — Background Distal hereditary motor neuronopathies (dHMN) are a group of genetic disorders characterised by motor neuron degeneration leading to muscle weakness ...

Based on the provided context, the differential diagnosis for autosomal recessive distal hereditary motor neuronopathy (dHMN) includes:

• Juvenile forms of amyotrophic lateral sclerosis (ALS)
• Hereditary spastic paraplegia
• Primary Lateral Sclerosis (PLS)

These conditions can present with similar symptoms and findings, such as muscle weakness and wasting, and may require careful differentiation to establish an accurate diagnosis.

According to [6], autosomal recessive distal hereditary motor neuronopathy-1 (HMNR1) is characterized by distal and proximal muscle weakness and diaphragmatic palsy that leads to respiratory failure. This condition can be distinguished from other forms of dHMN, such as HMND9, which typically presents with juvenile onset of slowly progressive distal muscle weakness and atrophy [3].

In addition, the differential diagnosis for dHMN may also include other conditions that affect motor neurons or muscles, such as spinal muscular atrophy (SMA) or hereditary sensory neuropathy (HSN).

It's worth noting that the clinical presentation and genetic characteristics of each condition can vary, and a comprehensive evaluation, including neurophysiologic testing, muscle MRI, muscle biopsy, and western blot of BAG3 protein in skeletal muscle, may be necessary to establish an accurate diagnosis [14][15].

References: [3] - HMND9 is an autosomal dominant neurologic disorder characterized by juvenile onset of slowly progressive distal muscle weakness and atrophy affecting both ... [6] - Autosomal recessive distal hereditary motor neuronopathy-1 (HMNR1) is characterized by distal and proximal muscle weakness and diaphragmatic palsy that leads to respiratory failure. [14][15] - Objective: To describe a new phenotype associated with a novel variant in BAG3: autosomal dominant adult-onset distal hereditary motor neuronopathy.