Brody myopathy

Brody myopathy can be caused by mutations in the gene ATP2A1 _gene . This gene provides instructions for making an enzyme called sarco(endo)plasmic reticulum calcium- ATPase 1 (SERCA1). Enzymes are proteins that accelerate chemical reactions within the body. The SERCA1 enzyme is found in skeletal muscles (muscles used for movement). It is involved in moving calcium around in the cell, which is important for normal muscle contraction. Mutations in the _ATP2A1 gene results in problems with calcium transportation in the cell, and ultimately problems with muscle contraction.

Not all people with Brody myopathy have mutations in the ATP2A1 gene. There are likely other gene mutations, that have not yet been identified, that can cause this disease.

Brody myopathy is suspected in people with the characteristic symptoms. The diagnosis may be confirmed using a combination of several different evaluations including:

• Physical examination
• Bloodwork to evaluate the level of certain proteins such as creatine kinase
• Muscle biopsy
• Electromyography

Most cases of Brody myopathy are inherited in an autosomal recessive manner. This means that to have the condition, a person must have a mutation in both copies of the responsible gene in each cell. People with Brody myopathy inherit one mutated copy of the gene from each parent, who is referred to as a carrier. Carriers of an autosomal recessive condition typically do not have any signs or symptoms (they are unaffected). When 2 carriers of an autosomal recessive condition have children, each child has a:

• 25% (1 in 4) chance to be affected
• 50% (1 in 2) chance to be an unaffected carrier like each parent
• 25% (1 in 4) chance to be unaffected and not be a carrier

Brody myopathy is a hereditary condition that affects the skeletal muscles (muscles used for movement). Symptoms typically begin in childhood and are characterized by muscle cramping and stiffening (myopathy) after exercise or other strenuous activity. These symptoms can worsen in cold temperatures and are usually painless, however, some individuals may have mild discomfort. Some cases of Brody myopathy are caused by mutations in the ATP2A1 gene. The cause of Brody myopathy for individuals not found to have an ATP2A1 gene mutation remains unknown. Brody myopathy is usually inherited in an autosomal recessive manner with a few reported cases of autosomal dominant inheritance. While there is no one treatment for Brody myopathy, certain muscle relaxants, such as dantrolene and blood pressure medications called calcium channel blockers, such as verapamil may be useful.

Some researchers suggest that individuals found to have an ATP2A1 gene mutation have a slightly different disorder in which symptoms appear at an earlier age. They use the disease term "Brody disease" for individuals with an identified mutation versus "Brody syndrome" for those that do not. More research may help clarify whether these are two different disorders or a variation of the same disorder.

Symptoms of Brody myopathy may remain the same or slowly worsen with time. In advanced disease some people may experience some muscle loss (atrophy) and weakness.

Brody myopathy is estimated to occur in 1 out of 10,000,000 people. Researchers suggest that this may be an underestimation as the diagnosis may go unrecognized.

There is no one treatment for Brody myopathy. Certain muscle relaxants, such as dantrolene and blood pressure medications called calcium channel blockers, such as verapamil have been used with varying levels of success.