Distal hereditary motor neuropathy, type V

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

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.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

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.

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 and family implications

From: MedlinePlus Genetics, National Library of Medicine

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.

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

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

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.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Distal amyotrophy · Frequent (79-30%)

Muscular atrophy affecting muscles in the distal portions of the extremities.

Distal lower limb muscle weakness · Frequent (79-30%)

Reduced strength of the distal musculature of the legs.

Impaired vibratory sensation · Frequent (79-30%)

A decrease in the ability to perceive vibration. Clinically, this is usually tested with a tuning fork which vibrates at 128 Hz and is applied to bony prominences such as the malleoli at the ankles or the metacarpal-phalangeal joints. There is a slow decay of vibration from the tuning fork. The degree of vibratory sense loss can be crudely estimated by counting the number of seconds that the examiner can perceive the vibration longer than the patient.

Thenar muscle atrophy · Frequent (79-30%)

Wasting of thenar muscles, which are located on palm of the hand at the base of the thumb.

Upper limb muscle weakness · Frequent (79-30%)

Weakness of the muscles of the arms.

Cold-induced hand cramps · Frequent (79-30%)

First dorsal interossei muscle atrophy · Frequent (79-30%)

First dorsal interossei muscle weakness · Frequent (79-30%)

Other findings in the same source

From: Orphanet

Additional reported features include Motor polyneuropathy (Frequent (79-30%)); Thenar muscle weakness (Frequent (79-30%)); Unsteady gait (Frequent (79-30%)); Hammertoe (Occasional (29-5%)); Hyperreflexia (Occasional (29-5%)); Pes cavus (Occasional (29-5%)); Pes valgus (Occasional (29-5%)); Abnormal motor nerve conduction velocity (Very rare (<4-1%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Distal hereditary motor neuropathy, type V is Neurology, with a neurologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Which nervous-system findings help explain the symptoms?
• Would an assessment of walking, communication or daily function be helpful?
• Are rehabilitation or other specialist services relevant?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Distal hereditary motor neuropathy, type V. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.