autosomal dominant distal hereditary motor neuronopathy 2

Autosomal Dominant Distal Hereditary Motor Neuronopathy 2 (HMND2)

Autosomal dominant distal hereditary motor neuronopathy 2, also known as HMND2, is a rare genetic disorder that affects the nerve cells in the spinal cord. It is characterized by a progressive degeneration of motor neurons, leading to muscle weakness and atrophy primarily in the distal limbs.

Key Features:

• Progressive Disorder: HMND2 is a slowly progressive disorder that affects nerve cells in the spinal cord.
• Muscle Weakness: The condition results in muscle weakness and affects movement, primarily in the legs.
• Distal Limb Involvement: Muscle weakening is less pronounced in the hands and forearms compared to the lower limbs.
• Age of Onset: The disease typically starts between the second and fifth decades of life.

Genetic Cause:

HMND2 is caused by a heterozygous mutation in the gene encoding heat-shock 22-kD protein-8 (HSPB8) on chromosome 12q24. This genetic mutation leads to the degeneration of motor neurons, resulting in muscle weakness and atrophy.

Prevalence:

The cumulative estimated prevalence of HMND2 is not well-documented, but it is considered a rare condition.

References:

• [1] Description. Distal hereditary motor neuropathy, type II is a progressive disorder that affects nerve cells in the spinal cord.
• [3] A number sign (#) is used with this entry because of evidence that distal autosomal dominant distal hereditary motor neuronopathy-2 (HMND2) is caused by heterozygous mutation in the gene encoding heat-shock 22-kD protein-8 (HSPB8; 608014) on chromosome 12q24.
• [10] A rare autosomal dominant distal hereditary motor neuropathy characterized by onset of slowly progressive distal limb weakness and atrophy between the second and fifth decades of life.

Muscle Weakness and Atrophy

Autosomal dominant distal hereditary motor neuropathy, type II is characterized by muscle weakness and wasting predominantly affecting the hands [5]. This condition results in significant muscle atrophy of the hands and lower limbs [7].

Distal Muscle Weakness

The disorder is marked by distal muscle weakness with curled fingers [6], which can lead to difficulties in performing daily activities. The muscles in the hands and forearms are often affected, making it challenging for individuals to perform tasks that require fine motor skills.

Foot Deformity

A common feature of this condition is foot deformity, specifically pes cavus [3]. This can lead to discomfort and difficulty walking or standing for extended periods.

Sensory Involvement

While sensory involvement is typically less pronounced or absent, some individuals may experience numbness or tingling sensations in the affected limbs. However, these symptoms are not as prominent as the motor symptoms.

Additional Features

In some cases, additional features such as spasticity and hyperreflexia, particularly in the lower limbs, may be present [4]. These features can overlap with those observed in Silver syndrome, an allelic disorder.

Progressive Nature

Distal hereditary motor neuropathy, type II is a progressive disorder that affects nerve cells in the spinal cord. It results in muscle weakness and affects movement, primarily in the legs [13].

The severity of this condition can vary among individuals, with some experiencing more pronounced symptoms than others. Early diagnosis and management are essential to slow down disease progression and improve quality of life.

References: [3] Foot deformity is a common feature. [4] Some patients show spasticity and hyperreflexia, mainly of the lower limbs: these features overlap with those observed in Silver syndrome, an allelic disorder. [5] A rare autosomal dominant distal hereditary motor neuropathy disease characterized by muscle weakness and wasting predominantly affecting the hands. [6] Signs include distal muscle weakness with curled fingers, pes cavus foot deformities (Fig. 180.1D), and diminished deep tendon reflexes. Neurophysiological ... [7] 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 ... [13] Distal hereditary motor neuropathy, type II is a progressive disorder that affects nerve cells in the spinal cord. It results in muscle weakness and affects movement, primarily in the legs.\n\nSome individuals with distal hereditary motor neuropathy, type II have weakening of the muscles in the hands and forearms.

Autosomal dominant distal hereditary motor neuronopathy, type II (dHMN-II) can be diagnosed through a combination of clinical presentation, family history, and genetic testing.

Clinical Presentation

• Muscle weakness and atrophy primarily in the legs, with some individuals experiencing weakening of muscles in the hands and forearms [2]
• Progressive disorder affecting nerve cells in the spinal cord, leading to muscle weakness and impaired movement [8]

Diagnostic Tests

• Nerve Conduction Studies: Reveals reduced motor amplitude potentials with no sensory abnormalities [5]
• Electromyography (EMG): May show a predominantly distal pattern of muscle denervation [5]
• Genetic Testing: Can be used to diagnose specific inherited peripheral neuropathies, including dHMN-II
  • Exome Sequencing with CNV Detection is a test method that can identify mutations in the HSPB1 and HSPB8 genes associated with dHMN-II [3]

Other Tests

• Neurophysiology testing may be used to support the diagnosis of dHMN-II, although it is not a definitive diagnostic tool
• Molecular Genetics Tests, such as Exome Sequencing with CNV Detection, can also be used to diagnose specific inherited peripheral neuropathies

It's worth noting that genetic testing can provide a definitive diagnosis for individuals suspected to have dHMN-II. However, the severity and progression of the condition can vary widely among affected individuals.

References:

[1] - Not applicable (no relevant information in search results) [2] - Context #2 [3] - Context #6 [5] - Context #5 [8] - Context #8

Based on the provided context, it appears that there are limited treatment options available for autosomal dominant distal hereditary motor neuronopathy 2 (dHMN2). However, some general information about the treatment approaches to Charcot-Marie-Tooth disease (CMT), which is a related condition, can be found in the search results.

• Reviews of treatment approaches to CMT [1] mention that there are no specific treatments for dHMNs, including dHMN2.
• A study on autosomal dominant juvenile amyotrophic lateral sclerosis and distal hereditary motor neuronopathy with pyramidal tract signs [13] suggests that these conditions may be synonyms for the same disorder, but no specific treatment is mentioned.
• Another study on the distal hereditary motor neuropathies (dHMN) [14] mentions that 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).

However, it's worth noting that some general treatment approaches for CMT may be applicable to dHMN2. These include:

• Physical therapy to maintain muscle strength and mobility [1]
• Occupational therapy to improve daily functioning [1]
• Pain management with medications such as gabapentin or pregabalin [1]

It's essential to consult a healthcare professional for personalized advice on managing symptoms and improving quality of life.

References: [1] Carter et al 2008, Young et al 2008, Reilly & Shy 2009 [13] Autosomal dominant juvenile amyotrophic lateral sclerosis and distal hereditary motor neuronopathy with pyramidal tract signs: synonyms for the same disorder Brain (2000) [14] The distal hereditary motor neuropathies (dHMN) comprise a heterogenous group of diseases that share the common feature of a length-dependent predominantly motor neuropathy.

The differential diagnosis for autosomal dominant distal hereditary motor neuronopathy (dHMN) type II involves a range of conditions that share similar clinical features. Some of the key conditions to consider are:

• Juvenile forms of amyotrophic lateral sclerosis (ALS): These can be caused by variations in genes associated with dHMN, as well as other genetic disorders.
• Hereditary spastic paraplegia: This condition affects the spinal cord and can present with similar symptoms to dHMN.
• X-linked bulbospinal neuronopathy (Kennedy's disease): Also known as spinobulbar muscular atrophy, this is a rare genetic disorder that affects motor neurons in the brain and spinal cord.
• Distal motor neuropathies: These are a group of conditions characterized by progressive muscle weakness and wasting, often affecting the distal muscles of the limbs.

It's worth noting that the differential diagnosis for dHMN type II can be complex and requires a comprehensive evaluation of clinical features, neurophysiologic testing, muscle MRI, muscle biopsy, and western blot analysis of BAG3 protein in skeletal muscle [14].

In terms of specific genes associated with dHMN, mutations in the HSPB8 gene have been identified as causing autosomal dominant distal hereditary motor neuropathy (HMND2) [7]. Additionally, a recurrent WARS mutation has been found to be a novel cause of autosomal dominant distal hereditary motor neuropathy [11].

Overall, the differential diagnosis for dHMN type II requires a careful consideration of these and other conditions, as well as genetic testing to identify specific causative genes.

References:

• [7] Züchner S. (2020). MFN2-HMSN is a classic axonal peripheral sensorimotor neuropathy, inherited in either an autosomal dominant (AD) manner (~90%) or an autosomal recessive (AR) ...
• [11] A recurrent WARS mutation is a novel cause of autosomal dominant distal hereditary motor neuropathy. Brain. 2017;140:1252–1266.
• [14] Christodoulou K, Zamba E, Tsingis M, et al. . A novel form of distal hereditary motor neuronopathy maps to ...