Distal hereditary motor neuropathy, type V

Description

Distal hereditary motor neuropathy, type V is a disorder that affects nerve cells (neurons) in the spinal cord. This condition specifically affects motor neurons, which are specialized cells that control muscle movement. Damage to motor neurons results in muscle weakness that worsens over time. In people with distal hereditary motor neuropathy, type V, this weakness primarily affects movement in the muscles that are furthest from the center of the body (distal muscles), such as the muscles in the hands and feet.

Signs and symptoms of distal hereditary motor neuropathy, type V usually begin during adolescence, but they can appear any time between infancy and the mid-30s. The first symptom of this condition is often cramps in the hands that are brought on by exposure to cold temperatures.

The characteristic features of distal hereditary motor neuropathy, type V are weakness and wasting (atrophy) of muscles of the hand, specifically on the side of the index finger near the thumb and in the palm of the hand at the base of the thumb.

About half of individuals with distal hereditary motor neuropathy, type V develop muscle weakness in the feet and lower legs. This can lead to problems with walking (gait disturbance), difficulty lifting the front part of the foot (foot drop), and a high foot arch (pes cavus).

People with distal hereditary motor neuropathy, type V can have exaggerated reflexes (hyperreflexia) or other disturbances in the nerves that are used to detect sensations (sensory neuropathy). Although sensory neuropathy is uncommon in people with distal hereditary motor neuropathy, type V, it is typical of a disorder called Charcot-Marie-Tooth disease. These two disorders have overlapping features and can also share a genetic cause. People with distal hereditary motor neuropathy, type V typically have a normal life expectancy.

Frequency

The prevalence of all types of distal hereditary motor neuropathy is estimated to be about 2 in 100,000 individuals. The specific prevalence of distal hereditary motor neuropathy, type V is unknown.

Causes

Variants (also called mutations) in multiple genes can cause distal hereditary motor neuropathy, type V. Most commonly, variants in the BSCL2 and GARS1 genes cause this condition.

The BSCL2 gene provides instructions for making a protein called seipin. Seipin is located in the membrane of a cell structure called the endoplasmic reticulum. The endoplasmic reticulum is involved in protein processing and transport. Variants in the BSCL2 gene likely lead to a change in the structure of seipin. Research indicates that the altered seipin proteins build up in the endoplasmic reticulum. This accumulation likely damages motor neurons, which leads to muscle weakness in the hands and feet.

Endoplasmic reticulum (ER). Credit: U.S. National Library of Medicine.

The GARS1 gene provides instructions for making an enzyme called glycine—tRNA ligase, which is involved in the production of proteins. Variants in this gene reduce the activity of glycine—tRNA ligase. Researchers believe that this reduction in activity may impair the transmission of nerve impulses. As a result, motor neurons slowly lose the ability to communicate with muscles in the hands and feet.

In rare instances, variants in other genes can cause distal hereditary motor neuropathy, type V.

Inheritance

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

Autosomal dominant inheritance. Credit: U.S. National Library of Medicine.

Some people who have the altered gene never develop the condition. This situation is known as reduced penetrance.

Other Names for This Condition

• DHMN5
• DHMNV
• Distal hereditary motor neuronopathy type 5
• Distal hereditary motor neuronopathy, type V
• Distal spinal muscular atrophy, type V
• DSMAV
• HMN V
• Spinal muscular atrophy, distal type V
• Spinal muscular atrophy, distal, with upper limb predominance

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