National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Brody myopathy


Other Names:
Brody disease; Sarcoplasmic reticulum -Ca2+ATPase deficiency
Categories:
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.[1][2] 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.[1][2][3] 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.[3] 

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.[1][4] More research may help clarify whether these are two different disorders or a variation of the same disorder.
Last updated: 7/29/2016
Symptoms of Brody myopathy typically begin in childhood. Children with this condition may have a hard time keeping up with their peers in physical activities. They have a difficult time relaxing muscles, first in their arms and legs, but then in their face and trunk. They may also have difficulty relaxing their eyelids and grip. These muscle symptoms worsen with exercise and exposure to cold weather.[5]

In people with Brody myopathy, the term “pseudomyotonia” is used to describe these muscle symptoms. The term “myotonia” refers to muscle stiffness or an inability to relax the muscles and can be evidenced by abnormal electromyography (EMG) results. In Brody myopathy, the EMG results are normal, even though the person show signs of the muscle stiffness. Because of the normal EMG results, the word “pseudo-myotonia” is used.[5]

Individuals with Brody myopathy sometimes develop myoglobinuria. Myoglobinuria occurs when exercise leads to the breakdown of muscle tissue and release of a protein called myoglobin into the urine. Myoglobin causes the urine to be red or brown.[2]

Last updated: 8/3/2016

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

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Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Autosomal recessive inheritance 0000007
Exercise-induced muscle stiffness
Muscle stiffness with exercise
Muscle stiffness, exercise-induced
[ more ] 		0008967
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Last updated: 7/1/2020
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.[6]

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.[2]
Last updated: 8/3/2016
Most cases of Brody myopathy are inherited in an autosomal recessive manner.[2] 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
Last updated: 8/3/2016
Brody myopathy is suspected in people with the characteristic symptoms. The diagnosis may be confirmed using a combination of several different evaluations including:[5][1]
  • Physical examination
  • Bloodwork to evaluate the level of certain proteins such as creatine kinase
  • Muscle biopsy
  • Electromyography
Last updated: 8/3/2016

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
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.[5][3]
Last updated: 8/3/2016
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.[5]
Last updated: 8/3/2016
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.[1][7]
Last updated: 8/3/2016

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Social Networking Websites

  • Contact a Family is a UK-wide charity providing advice, information and support to individuals affected by various health conditions. They enable parents, families, and individuals to get in contact with others, on a local, national, and international basis. Each year they reach at least 275,000 families. Click on Contact a Family to view the Making Contact page for Brody disease.

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Brody myopathy. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know. Submit a new question

  • Could you tell me in laymen's terms what is Brody disease? See answer


  1. Voermans NC, Laan AE, Oosterhof A, van Kuppevelt TH, Drost G, Lammens M, Kamsteeg EJ, Scotton C, Gualandi F, Guglielmi V, van den Heuvel L, Vattemi G, van Engelen BG. Brody syndrome: a clinically heterogeneous entity distinct from Brody disease: a review of literature and a cross-sectional clinical study in 17 patients. Neuromuscul Disord. Nov 2012; 22(11):944-954. http://www.ncbi.nlm.nih.gov/pubmed/22704959.
  2. Brody myopathy. Genetics Home Reference. January 2012; https://ghr.nlm.nih.gov/condition/brody-myopathy.
  3. Victor A. McKusick. Brody myopathy. In: Marla J. F. O'Neill. OMIM. 6/10/2011; http://www.omim.org/entry/601003.
  4. Guglielmi V, Vattemi G, Gualandi F, Voermans NC, Marini M, Scotton C, Pegoraro E, Oosterhof A, Kósa M, Zádor E, Valente EM, De Grandis D, Neri M, Codemo V, Novelli A, van Kuppevelt TH, Dallapiccola B, van Engelen BG, Ferlini A, Tomelleri G. SERCA1 protein expression in muscle of patients with Brody disease and Brody syndrome and in cultured human muscle fibers. Mol Genet Metab. 2013 Sep-Oct; 110(1-2):162-169. http://www.ncbi.nlm.nih.gov/pubmed/23911890.
  5. Rose M, Griggs RC. Hereditary Nondegernative Neuromuscular Disease. In: Goetz CG . Textbook of Clinical Neurology, 3rd ed. Philadelphia PA: Saunders; 2007;
  6. ATP2A1. Genetics Home Reference. January 2012; https://ghr.nlm.nih.gov/gene/ATP2A1.
  7. MacLennan DH. Ca2+ signalling and muscle disease. Eur J Biochem. Sep 2000; 267(17):5291-7. http://www.ncbi.nlm.nih.gov/pubmed/10951187.