autosomal recessive distal hereditary motor neuronopathy 4

Autosomal Recessive Distal Hereditary Motor Neuronopathy 4 (dHMN4)

Autosomal recessive distal hereditary motor neuronopathy 4, also known as dHMN4, is a rare genetic neuromuscular disease characterized by progressive weakness and wasting of the muscles in the feet and hands. This condition typically begins in childhood or adolescence and can lead to severe muscle atrophy, contractures, scoliosis, hyperlordosis, and respiratory insufficiency requiring assisted ventilation.

Clinical Features

• Proximal muscle weakness, particularly in the feet and hands
• Rapid progression to generalized areflexic tetraplegia
• Contractures and severe scoliosis
• Hyperlordosis
• Respiratory insufficiency requiring assisted ventilation

Genetic Basis

dHMN4 is caused by mutations in the PLEKHG5 gene, which codes for a protein involved in the regulation of muscle function. The disease is inherited in an autosomal recessive pattern, meaning that individuals must inherit two copies of the mutated gene (one from each parent) to develop the condition.

Diagnostic Criteria

Diagnosis of dHMN4 can be made based on clinical features, genetic testing, and exclusion of other neuromuscular disorders. Genetic testing for PLEKHG5 mutations is available in some laboratories around the world.

Practice Guidelines and Resources

For more information on dHMN4, including practice guidelines and authoritative resources, please refer to:

• GeneReviews
• PubMed
• MedlinePlus
• clinicaltrials.gov
• PharmGKB

References: [2][3][5][6][9]

Based on the search results, here are the signs and symptoms of autosomal recessive distal hereditary motor neuronopathy 4:

Muscle Weakness and Atrophy

• The disease starts with weakness and wasting in the distal leg muscles, later progressing to proximal leg and distal upper limb muscles [2].
• Patients typically develop foot drop, pes varus, hammer toes and claw hands [8].

Motor Neuron Degeneration

• Distal hereditary motor neuronopathies (dHMN) comprise a heterogenous group of diseases that share the common feature of a length-dependent predominantly motor neuropathy [11].
• Hereditary motor neuropathies (HMN) are characterized by slowly progressive, length-dependent distal muscle weakness and atrophy [12].

Other Symptoms

• Foot deformities and calf atrophy are commonly observed [5].
• Distal amyotrophy; Distal muscle weakness with curled fingers, pes cavus foot deformities, and diminished deep tendon reflexes are also seen [6][7].

It's worth noting that intellectual development, cognitive function, and brain imaging are typically normal in patients with autosomal recessive distal hereditary motor neuronopathy 4 [5].

Based on the provided context, diagnostic tests for autosomal recessive distal hereditary motor neuronopathy 4 (dHMN4) can be used to confirm a diagnosis.

• Genetic testing: Molecular genetic testing can detect mutations in the PLEKHG5 gene, which is associated with dHMN4. This test can confirm a diagnosis of dHMN4 when two pathogenic or likely pathogenic variants are detected in the autosomal recessive gene [11].
• Neurophysiology testing: Neurophysiology testing may reveal reduced motor amplitude potentials with no sensory abnormalities, and electromyography (EMG) testing may show a predominantly distal pattern of muscle involvement [7].
• Nerve conduction studies: These studies can also be used to diagnose dHMN4, in addition to clinical presentation, nerve conduction studies, and family history [4].

It's worth noting that an accurate diagnosis of dHMN4 through genetic testing can prevent the need for invasive diagnostic tests, such as nerve biopsies and lumbar punctures, and also prevent a trial of potentially dangerous immunosuppressive therapy in certain situations [12].

Based on the provided context, it appears that there are some potential treatment approaches for autosomal recessive distal hereditary motor neuronopathy (dHMN) type 4.

• According to search result [10], variants in MME are associated with autosomal-recessive distal hereditary motor neuropathy. However, this does not provide information on the drug treatment.
• Search result [14] mentions recent therapeutic advances in hereditary neuropathy, including the use of lipid nanoparticle sequestered antisense oligonucleotides in CMT1A and lipid nanoparticle delivered coenzyme Q10. However, it is unclear if these treatments are specifically for autosomal recessive dHMN type 4.
• Search result [12] mentions recent therapeutic advances in hereditary motor neuropathy and CMT2, including the use of coenzyme Q10. This suggests that coenzyme Q10 may be a potential treatment option for some forms of dHMN.

It is essential to note that these findings are based on limited information and more research is needed to determine the most effective treatments for autosomal recessive dHMN type 4.

Potential Treatment Options:

• Coenzyme Q10 (search result [12])
• Lipid nanoparticle sequestered antisense oligonucleotides in CMT1A (search result [14])
• Lipid nanoparticle delivered coenzyme Q10 (search result [14])

Please consult a medical professional for personalized advice on treating autosomal recessive dHMN type 4.

The differential diagnosis for autosomal recessive distal hereditary motor neuronopathy 4 (HMND4) involves considering other conditions that may present with similar symptoms.

According to the search results, the differential diagnosis for HMND4 includes:

• Juvenile forms of amyotrophic lateral sclerosis (ALS), which can be caused by variations in certain genes [1].
• Hereditary spastic paraplegia, another genetic disorder that affects motor neurons.
• Other forms of distal hereditary motor neuropathies (dHMNs), which are a group of neuromuscular disorders caused by anterior horn cell degeneration [11].

It's also worth noting that the diagnosis of HMND4 is often achieved through genetic testing, and mutations in specific genes such as HSPB1, GARS1, BICD2, and DNAJB2 have been identified as common causes of dHMNs [10].

In terms of clinical presentation, distal hereditary motor neuropathies like HMND4 typically present with progressive muscle weakness and atrophy, particularly in the distal muscles of the limbs. However, it's essential to rule out other conditions that may cause similar symptoms.

References:

[1] 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] Mutations in HSPB1 (10.4%), GARS1 (9.8%), BICD2 (8.0%), and DNAJB2 (6.7%) genes were the most frequent cause of distal hereditary motor neuropathies. [11] Distal hereditary motor neuronopathy (dHMN or HMN) is a heterogeneous group of neuromuscular disorders caused by anterior horn cell degeneration.