Distal hereditary motor neuropathy, type II
Distal hereditary motor neuropathy, type II is a progressive genetic disorder that damages motor neurons, leading to muscle weakness and wasting primarily in the lower legs.
Overview
Distal hereditary motor neuropathy, type II is a progressive disorder that affects nerve cells 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. The weakness associated with this condition primarily affects movement in the legs.
Symptoms
The signs and symptoms of distal hereditary motor neuropathy, type II often begin in adolescence to mid-adulthood. Common symptoms and progression of the disorder include:
- Initial cramps or weakness in the muscles of the big toe, which later spreads to the entire foot.
- A gradual loss of muscle tissue (atrophy) in the lower legs over the next 5 to 10 years.
- Problems with walking (gait disturbance) and the development of high arches.
- Potential paralysis of the lower legs over time.
- Later and less severe muscle atrophy in the thigh muscles.
- Weakening of the muscles in the hands and forearms, which is typically less severe than lower limb weakness and rarely leads to paralysis.
- Exaggerated reflexes (hyperreflexia).
- Minor disturbances in the nerves used to detect sensations (sensory neuropathy), which is uncommon and typically associated with a related disorder called Charcot-Marie-Tooth disease.
- In rare cases, hearing loss.
Frequency
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 approximately 8 to 15 percent of all these cases.
Causes & Genetics
Variants (also called mutations) in multiple genes can cause this condition. Most commonly, variants in the HSPB1 and HSPB8 genes are responsible. These genes provide instructions for making proteins called heat shock proteins (specifically, heat shock protein beta-1 and heat shock protein beta-8).
Heat shock proteins help protect cells under stress from factors such as infection, inflammation, toxins, elevated temperature, injury, and disease. They are also involved in:
- Stabilizing the cell's structural framework (the cytoskeleton).
- Folding and stabilizing newly produced proteins.
- Repairing damaged proteins.
- Assisting in the tensing of muscle fibers (muscle contraction).
- Maintaining the structure of neurons.
Gene variants in HSPB1 and HSPB8 typically change single protein building blocks (amino acids), causing the proteins to form clusters (aggregates). These aggregates build up and impair cell function, particularly in motor neurons. Additionally, neurons lacking functional heat shock proteins become vulnerable to stress and damage, making them more likely to die off over time.
In rare cases, variants in other genes can also cause the condition.
Associated Genes
- HSPB1
- HSPB8
- FBXO38
- HSPB3
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.
Other Names for This Condition
- Distal hereditary motor neuronopathy, type II
- HMN II
- HMN2
- HMND2
