Disease Profile

Brody myopathy

Prevalence ?
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
<1 / 1 000 000

< 331

US Estimated

< 514

Europe Estimated

Age of Onset

Adolescent

ICD-10

G71.8

Inheritance

Autosomal dominant ?A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive ?Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked dominant ?X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked recessive ?Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic ?Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor ?Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other Names (AKA)

Brody disease; Sarcoplasmic reticulum -Ca2+ATPase deficiency

Categories

Congenital and Genetic Diseases; Musculoskeletal Diseases; Nervous System Diseases

Summary

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.

Symptoms

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]

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.

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

Cause

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]

Diagnosis

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

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.

    Treatment

    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]

    Organizations

    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.

    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.

      Organizations Providing General Support

        Learn More

        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.

            References

            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. https://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; https://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. https://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. https://www.ncbi.nlm.nih.gov/pubmed/10951187.