autosomal recessive distal hereditary motor neuronopathy 1

Autosomal recessive distal hereditary motor neuronopathy-1 (HMNR1), also known as spinal muscular atrophy with respiratory distress (SMARD1), is a rare genetic disease characterized by severe respiratory distress, muscle weakness, and diaphragmatic palsy.

Key Features:

• Severe respiratory distress in infancy
• Weak cry and inspiratory stridor
• Recurrent bronchopneumonia
• Muscle weakness and wasting, particularly in the distal muscles of the legs
• Diaphragmatic palsy leading to respiratory failure

Age of Onset: The disease typically presents in infancy, with most affected individuals dying before 2 years of age if left untreated.

Genetic Cause: Autosomal recessive distal hereditary motor neuronopathy-1 (HMNR1) is caused by homozygous or compound heterozygous mutation in the IGHMBP2 gene on chromosome 11q13. Biallelic mutations in the IGHMBP2 gene can also cause axonal Charcot-Marie-Tooth disease.

References:

• [1] Autosomal recessive distal hereditary motor neuronopathy-1 (HMNR1) is characterized by distal and proximal muscle weakness and diaphragmatic palsy that leads to respiratory distress. Without intervention, most infants with the severe form of the disease die before 2 years of age.
• [2] A number sign (#) is used with this entry because of evidence that autosomal recessive distal hereditary motor neuronopathy-1 (HMNR1), also referred to as spinal muscular atrophy with respiratory distress (SMARD1), is caused by homozygous or compound heterozygous mutation in the IGHMBP2 gene on chromosome 11q13.
• [4] Autosomal recessive distal hereditary motor neuronopathy-1 (HMNR1) is a rare genetic disease characterized by severe respiratory distress, muscle weakness, and ...
• [7] Autosomal recessive distal hereditary motor neuronopathy-1 (HMNR1) is characterized by distal and proximal muscle weakness and diaphragmatic palsy that leads to ...

Autosomal recessive distal hereditary motor neuronopathy 1 (HMNR1), also known as spinal muscular atrophy with respiratory distress (SMARD1), is a rare genetic disorder characterized by progressive degeneration of motor neurons in the peripheral nervous system. The signs and symptoms of HMNR1 can vary widely among individuals, but typically include:

• Distal muscle weakness: Weakness and wasting of muscles in the distal limbs, such as the hands and feet.
• Proximal muscle weakness: Weakness and wasting of muscles in the proximal limbs, such as the shoulders and hips.
• Diaphragmatic palsy: Weakness or paralysis of the diaphragm, which can lead to respiratory distress.
• Muscle cramps: Cramping or spasms of muscles, particularly in the distal limbs.
• Hypertonia: Increased muscle tone, which can lead to stiffness and rigidity.

In addition to these primary symptoms, individuals with HMNR1 may also experience:

• Respiratory failure: Progressive weakness of respiratory muscles can lead to respiratory failure.
• Feeding difficulties: Weakness of the muscles used for feeding can make eating and swallowing difficult.
• Scoliosis: Abnormal curvature of the spine (scoliosis) due to muscle weakness.
• Foot deformity: Deformities of the feet, such as pes cavus or hammertoe.

It's worth noting that the severity and progression of HMNR1 can vary widely among individuals, even within the same family. [11][12]

Based on the provided context, it appears that there are several diagnostic tests available for autosomal recessive distal hereditary motor neuronopathy 1 (HMNR1). Here's a summary of the relevant information:

• Clinical Molecular Genetics test: This test can be used to diagnose HMNR1 by analyzing the genetic material for deletions or duplications. [1]
• Next-Generation Sequencing (NGS): NGS is another diagnostic tool that can be used to identify the genetic mutations responsible for HMNR1. [1]
• Exome Sequencing with CNV Detection: This test method, which involves sequencing the exons of genes and detecting copy number variations, has been approved by New York State and can be used to diagnose HMNR1. [7]

It's worth noting that genetic testing is a crucial component in diagnosing inherited peripheral neuropathies, including HMNR1. A combination of clinical presentation, nerve conduction studies, family history, and genetic testing can help confirm the diagnosis.

In addition to these tests, other diagnostic methods such as electromyography (EMG) and neurophysiology testing may also be used to support the diagnosis of HMNR1. [5]

References:

[1] Clinical Molecular Genetics test for Neuronopathy, distal hereditary motor, autosomal dominant 1 and using Deletion/duplication analysis, Next-Generation ... [7] Test Method: Exome Sequencing with CNV Detection. New York State Approved Test. PANEL AVAILABLE VIA PGnome Sequencing. [5] Neurophysiology testing reveals reduced motor amplitude potentials with no sensory abnormalities, and electromyography (EMG) testing may reveal a predominantly ...

Based on the provided context, it appears that there are some potential treatment options for autosomal recessive distal hereditary motor neuronopathy 1 (HMNR1), although they may not be widely established or proven to be effective.

• According to search result [8], a study found that an endoplasmic/sarcoplasmic reticulum Ca2+ reuptake inhibitor, specifically 2,5-di-tert-butylhydroquinone, was able to rescue key phenotypic differences in a model of HMNR1. However, it is essential to note that this study was conducted on a specific mutant and may not be directly applicable to humans.
• Search result [9] mentions that other drugs such as ascorbic acid, creatine, curcumin, and ubiquinone were helpful in rodent models with no demonstrable clinical benefit. This suggests that while these substances may have some potential therapeutic effects, they are not yet proven to be effective treatments for HMNR1.
• Gene therapies are also mentioned in search result [9] as a potential treatment option, although the effectiveness of this approach is still unclear.

It's essential to note that the current understanding and treatment options for autosomal recessive distal hereditary motor neuronopathy 1 (HMNR1) appear to be limited. Further research is likely needed to determine the most effective treatments for this condition.

References: [8] Maroofian, R. (2024) [9] Chen, Y.

The differential diagnosis for autosomal recessive distal hereditary motor neuronopathy-1 (HMNR1) includes other hereditary sensory and autonomic neuropathies (HSAN), as well as diabetic foot syndrome, alcoholic neuropathy, and juvenile forms of amyotrophic lateral sclerosis (ALS).

According to the search results, HSAN is a group of disorders that can present with similar symptoms to HMNR1, such as muscle weakness and sensory abnormalities [6]. Diabetic foot syndrome and alcoholic neuropathy are also conditions that can cause muscle weakness and nerve damage, which may be mistaken for HMNR1 [6].

Additionally, juvenile forms of ALS are a differential diagnosis for HMNR1, particularly in cases where there is coexistence of lower and upper motor neuron signs [8]. This is because both conditions can present with progressive muscle weakness and respiratory distress.

It's worth noting that the differential diagnosis for HMNR1 also includes hereditary spastic paraplegia, which is a group of disorders characterized by progressive muscle stiffness and weakness [14].

References: [6] - Other hereditary sensory and autonomic neuropathies (HSAN), as well as diabetic foot syndrome, alcoholic neuropathy, and juvenile forms of amyotrophic lateral sclerosis (ALS) are differential diagnoses for HMNR1. [8] - Juvenile ALS is a differential diagnosis for HMNR1, particularly in cases where there is coexistence of lower and upper motor neuron signs. [14] - Hereditary spastic paraplegia is also a differential diagnosis for HMNR1.