autosomal recessive distal hereditary motor neuronopathy

Autosomal Recessive Distal Hereditary Motor Neuronopathy (HMNR): A Rare Neuromuscular Disorder

Autosomal recessive distal hereditary motor neuronopathy, also known as HMNR, is a rare neuromuscular disorder characterized by progressive muscle weakness and atrophy predominantly affecting the lower limbs. This condition 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 disease.

Key Features:

• Progressive Muscle Weakness: HMNR is characterized by slowly progressive muscle weakness and atrophy, primarily affecting the lower limbs.
• Distal Involvement: The disorder typically affects the distal muscles (those farthest from the center of the body), such as those in the hands and feet.
• Gait Abnormalities: As the disease progresses, individuals may experience difficulty walking due to muscle weakness and atrophy in the lower limbs.
• Upper Limb Involvement: Upper limb involvement often occurs, with weakness and atrophy of the hand muscles.

Age of Onset:

The age of onset for HMNR can vary, but it typically begins in childhood or adolescence. However, later adult-onset cases have been reported.

Genetic Heterogeneity:

HMNR is a genetically heterogeneous disorder, meaning that different mutations in various genes can cause the disease. The IGHMBP2 gene on chromosome 11q13 has been associated with autosomal recessive distal hereditary motor neuronopathy-1 (HMNR1), also known as spinal muscular atrophy with respiratory distress (SMARD1).

References:

• [3] Young adult-onset distal hereditary motor neuropathy is a rare autosomal recessive distal hereditary motor neuropathy characterized by slowly progressive.
• [10] 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.
• [11] Autosomal recessive distal hereditary motor neuronopathy-8 (HMNR8), or sorbitol dehydrogenase deficiency with peripheral neuropathy (SORDD), is characterized by onset of distal muscle weakness mainly affecting the lower limbs and resulting in difficulty walking.

Note: The citations refer to the corresponding search results provided in the context.

Autosomal recessive distal hereditary motor neuronopathy (HMNR7) presents with a range of signs and symptoms, primarily affecting the lower limbs.

Initial Symptoms

• Cramps or weakness in the muscles of the big toe, which can progress to involve the entire foot [1].
• Lower leg weakness typically begins in the first decade of life [3].

Common Features

• Foot deformity is a common feature, with calf atrophy and pes cavus (high-arched) foot deformities often observed [6].
• Muscle wasting and weakness are predominantly seen in the lower limbs.
• Hypo- or hyperreflexia may be present, indicating abnormal nerve function.

Additional Features

• In some cases, "complicated" distal HMN can involve additional features, such as:
  • Predominant hand involvement [5].
  • Vocal cord paralysis [5].
  • Respiratory distress or diaphragmatic palsy [4].

Other Signs and Symptoms

• Distal muscle weakness with curled fingers.
• Difficulty heel-walking due to foot drop.
• Gait difficulties.
• Axonal neuropathy seen on electrophysiologic studies.
• Length-dependent motor neuropathy.

It's essential to note that intellectual development, cognitive function, and brain imaging are typically normal in individuals with autosomal recessive distal hereditary motor neuronopathy [6].

Diagnostic Tests for Autosomal Recessive Distal Hereditary Motor Neuronopathy

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

Genetic Testing

• Exome Sequencing with CNV Detection: This test method involves analyzing the entire coding region of the genes associated with Charcot-Marie-Tooth disease, including those that cause autosomal recessive dHMN (1) [5].
• Deletion/Duplication Analysis: This test can identify deletions or duplications in specific genes that may be causing the condition (2).
• Sequence Analysis of the Entire Coding Region: This test involves analyzing the entire coding region of the genes associated with autosomal recessive dHMN to identify any mutations (29).

Other Diagnostic Tests

• Neurophysiology testing: This test can reveal reduced motor amplitude potentials and no sensory abnormalities, which is consistent with autosomal recessive dHMN (6).
• Electromyography (EMG) testing: EMG may show a predominantly axonal neuropathy pattern, which is characteristic of autosomal recessive dHMN (6).

Clinical Presentation

In addition to genetic testing, clinical presentation and family history are also important factors in diagnosing autosomal recessive dHMN. Young adult-onset distal hereditary motor neuropathy, a rare form of the condition, can be diagnosed based on its characteristic clinical features (8).

References

• GeneDx will extract DNA from the blood sample and analyze it by searching for variants in a number of genes associated with Charcot-Marie-Tooth, distal hereditary motor neuronopathies, including autosomal recessive dHMN (9).
• The estimated pooled prevalence of HMNs is 2.14/100 000, and around 30 causative genes have been identified, including forms inherited in an autosomal dominant, recessive, and X-linked pattern [13].
• Harding (1993) classified autosomal recessive distal hereditary motor neuronopathy as dHMN IV (HMN4) and dHMN III (HMN3), which differ only by less severe involvement in HMN3 [15].

Based on the provided context, it appears that there are some potential treatment approaches

The differential diagnosis of autosomal recessive distal hereditary motor neuronopathy (dHMN) involves distinguishing it from other neuromuscular disorders that may present with similar symptoms.

According to the search results, the differential diagnosis of dHMN includes:

• Juvenile forms of amyotrophic lateral sclerosis (ALS), which can be caused by variations in the same genes as dHMN [1]
• Hereditary spastic paraplegia, another neuromuscular disorder that affects motor neurons
• Spinal muscular atrophy (SMA), an autosomal recessive motor neuronopathy of childhood [5]

It's also worth noting that muscle MRI can be a supportive tool in guiding the differential diagnosis between dHMN and other neuromuscular disorders [2].

In terms of genetic counseling, it's essential to determine the mode of inheritance in each family and results of molecular genetic testing to provide accurate risk assessment for family members [4].

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. [2] Muscle MRI might represent a supportive tool to guide the differential diagnosis between distal ... [4] CMT hereditary neuropathy can be inherited in an autosomal dominant, autosomal recessive, or X-linked manner. Genetic counseling regarding risk to family members depends on accurate diagnosis, determination of the mode of inheritance in each family, and results of molecular genetic testing. [5] Patients with pure motor ... spinal muscular atrophy (SMA) is the autosomal recessive motor neuronopathy of childhood.