Distal hereditary motor neuropathy, type II

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Distal hereditary motor neuropathy, type II is a progressive disorder that affects nerve cells (neurons) in the brain and 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. Distal hereditary motor neuropathy, type II weakness primarily affects movement in the legs.

The signs and symptoms of distal hereditary motor neuropathy, type II often begin in adolescence to mid-adulthood. The initial symptoms of the disorder are cramps or weakness in the muscles of the big toe and, later, the entire foot. During the next 5 to 10 years, affected individuals experience a gradual loss of muscle tissue (atrophy) in the lower legs, which can lead to problems with walking (gait disturbance) and high arches (pes cavus). Over time, the lower legs may become paralyzed. The thigh muscles may also undergo muscle atrophy, although this generally occurs later and is less severe than the muscle atrophy in the lower legs.

Some individuals with distal hereditary motor neuropathy, type II can also experience weaken the muscles in the hands and forearms. This weakening is less severe than the weakening in the lower limbs and does not usually lead to paralysis. In rare cases, affected individuals experience hearing loss.

People with distal hereditary motor neuropathy, type II can have exaggerated reflexes (hyperreflexia) or other minor disturbances in the nerves used to detect sensations (sensory neuropathy). Sensory neuropathy is uncommon in people with distal hereditary motor neuropathy, type II and is typically a feature of a disorder called Charcot-Marie-Tooth disease. These two disorders have overlapping features and can also share a genetic

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 II. Most commonly, variants in the HSPB1 and HSPB8 genes cause this condition. These genes provide instructions for making proteins called heat shock proteins. Heat shock protein beta-1 is made from the HSPB1 gene, and heat shock protein beta-8 is made from the HSPB8 gene. Heat shock proteins help protect cells that are under stress from factors such as infection, inflammation, exposure to toxins, elevated temperature, injury, and disease. In addition, these proteins appear to be involved in stabilizing the cell's structural framework (the cytoskeleton), folding and stabilizing newly produced proteins, and repairing damaged proteins. Heat shock proteins also seem to play a role in the tensing of muscle fibers (muscle contraction).

Heat shock protein beta-1 and heat shock protein beta-8 are found in cells throughout the body. These proteins help fold newly produced proteins and refold damaged proteins. These proteins are also involved in maintaining the structure of neurons.

The HSPB1 and HSPB8 gene variants that cause distal hereditary motor neuropathy, type II typically lead to changes in single protein building blocks (amino acids) in the proteins. These changes can cause the proteins to form clusters (aggregates). These aggregates can build up and impair the function of cells, particularly motor neurons. In addition, neurons that do not have functional versions of these heat shock proteins are vulnerable to stress and cell damage. As a result, these cells are more likely to die off over time, leading to the signs and symptoms of distal hereditary motor neuropathy, type II.

In rare cases, variants in other genes can cause distal hereditary motor neuropathy, type II.

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.

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. Distal hereditary motor neuropathy, type II accounts for 8 to 15 percent of all cases of distal hereditary motor neuropathy.

Which doctor should you see?

The suggested department for discussing Distal hereditary motor neuropathy, type II 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 II. 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.