CAV3-Related Distal Myopathy
CAV3-related distal myopathy is a rare genetic muscle disorder characterized by weakness and wasting of the hands and feet, often accompanied by hyper-reactive muscle contractions.
Overview & Symptoms
CAV3-related distal myopathy is one form of distal myopathy, a group of disorders characterized by weakness and loss of function affecting the muscles farthest from the center of the body (distal muscles), such as those of the hands and feet. People with this condition experience wasting (atrophy) and weakness of the small muscles in the hands and feet that generally become noticeable in adulthood.
Key symptoms of the condition include:
- Wasting and weakness of the small muscles in the hands and feet
- Repetitive tensing of the muscles, especially in the forearms, in response to a bump or sudden impact (percussion-induced rapid contraction), which can continue for up to 30 seconds and may be painful
- Overgrowth (hypertrophy) of the calf muscles
The muscles closer to the center of the body (proximal muscles), such as the thighs and upper arms, remain normal in this condition.
Frequency
The prevalence of CAV3-related distal myopathy is unknown. Only a few affected individuals have been described in the medical literature.
Causes & Genetic Factors
CAV3-related distal myopathy is part of a group of conditions called caveolinopathies, which are muscle disorders caused by mutations in the CAV3 gene. The CAV3 gene provides instructions for making a protein called caveolin-3, which is found in the membrane surrounding muscle cells. This protein is the main component of caveolae, which are small pouches in the muscle cell membrane. Within the caveolae, the caveolin-3 protein acts as a scaffold to organize other molecules that are important for cell signaling and maintenance of the cell structure.
Mutations in the CAV3 gene result in a shortage of caveolin-3 protein in the muscle cell membrane and a reduction in the number of caveolae. A shortage of caveolae impairs the structural integrity of muscle cells, interferes with cell signaling, and causes the self-destruction of cells (apoptosis). The resulting degeneration of muscle tissue leads to the signs and symptoms of the condition.
In addition to CAV3-related distal myopathy, CAV3 gene mutations can cause other caveolinopathies, including:
- Limb-girdle muscular dystrophy
- Rippling muscle disease
- Isolated hyperCKemia
- A heart disorder called hypertrophic cardiomyopathy
It is unclear why a single CAV3 gene mutation may cause different patterns of signs and symptoms, even within the same family.
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. In most cases, an affected person has a parent with CAV3-related distal myopathy or another caveolinopathy. Rare cases result from new mutations in the gene and occur in people with no history of caveolinopathies in their family.
Other Names for This Condition
- Distal myopathy, Tateyama type
- MPDT