Tubular aggregate myopathy

Tubular aggregate myopathy (TAM) is usually inherited in an autosomal dominant manner, but autosomal recessive inheritance has also been reported.^[1][2][3]

Autosomal dominant inheritance means that having a mutation in only one copy of the responsible gene in each cell is enough to cause features of the condition. In some cases, an affected person inherits the mutated gene from an affected parent. In other cases, the mutation occurs for the first time in a person with no family history of the condition. This is called a de novo mutation. When a person with a mutation that causes an autosomal dominant condition has children, each child has a 50% (1 in 2) chance to inherit that mutation. Mutations in the STIM1 and ORAI1 genes have been shown to cause autosomal dominant TAM.^[4][5]

Autosomal recessive inheritance means that to be affected, a person must have a  mutation in both copies of the responsible gene in each cell. Affected people 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% chance to be affected
• 50% chance to be an unaffected carrier like each parent
• 25% chance to be unaffected and not a carrier

To our knowledge, the gene, or genes, responsible for autosomal recessive TAM have not yet been identified.

People with personal questions about the genetic cause and inheritance of this condition are encouraged to speak with a genetic counselor or other genetics professional. A genetics professional can help by:

• thoroughly evaluating the family history
• addressing questions and concerns
• assessing recurrence risks
• facilitating genetic testing if desired

Currently, the diagnosis of tubular aggregate myopathy (TAM) is made by identifying tubular aggregates in a muscle biopsy (the "hallmark" of TAM).^[6] Tubular aggregates are clumps of tube-like structures formed by the abnormal build-up of proteins.^[1] Other tests that may be used to support or rule out the diagnosis (or conditions with overlapping symptoms) include a blood test for creatine kinase (CK) levels or MRI of the muscles.^[7] If you are interested in being evaluated or finding out more about the diagnosis of TAM, we recommend asking your doctor for a referral to a specialist with experience in diagnosing myopathies and other muscle disorders.

Genetic testing for TAM may be possible, as currently there are 2 genes known to be responsible for TAM - the STIM1 and ORAI1 genes. However, some people with TAM do not have mutations in either of these genes. Additionally, specific mutations in these genes may alternatively be responsible for other disorders. The Genetic Testing Registry (GTR) provides information about the genetic tests available for TAM. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about genetic testing should contact a health care provider or a genetics professional.

The symptoms and severity of tubular aggregate myopathy (TAM) can vary from person to person, even within the same family.^[8][4] Some individuals may even appear asymptomatic.^[4] In general, the disorder is slowly progressive and chronic.^[8] We are not aware of information in the literature regarding the life expectancy of people with TAM. However, we did not come across any reports of a shortened lifespan in affected individuals.

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by the American College of Medical Genetics and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.