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Disease Profile

Myofibrillar 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.

Unknown

Age of onset

Adult

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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)

Desminopathy (type); Alpha Beta crystallinopathy (type); Myotilinopathy (type);

Summary

Myofibrilar myopathy (MFM) is a neuromuscular disease characterized by slowly progressive muscle weakness that can involve both proximal muscles (such as hips and shoulders) and distal muscles (those further away from the trunk). Some affected individuals also experience muscle stiffness, aching, or cramps. Other symptoms that can be associated with MFM include pain and tingling in the limbs (peripheral neuropathy) or an enlarged and weakened heart (cardiomyopathy).[1] Most people with MFM begin to develop muscle weakness in mid-adulthood, but features of the disease can appear anytime between infancy and late adulthood.[1][2] 

MFM is caused by a mutation (change) in any of several genes, including DESCRYAB, MYOTLDB3FLNCBAG3FHL1TTNand DNAJB6.[1][3] The signs and symptoms of MFM can vary depending on the genetic cause. For some people, the exact genetic cause may be unknown.[1] The mode of inheritance of the disease depends on exactly which gene is changed. MFM can be diagnosed with a muscle biopsy or other studies of muscle function. The diagnosis can be confirmed with genetic testing.[1] Treatment may include physical therapy and assistive devices such as a cane or wheelchair for those with advanced muscle weakness. Affected individuals who have cardiomyopathy or an abnormal heart rhythm (arrhythmia) may require a pacemaker or implantable cardioverter defibrillator (ICD).[1]

Symptoms

Myofibrillar myopathy (MFM) primarily affects skeletal muscles, which are muscles that the body uses for movement. In some cases, the heart (cardiac) muscle is also affected. The signs and symptoms of MFM vary among affected individuals, typically depending on the exact genetic cause of the disease. Most people with this disease begin to develop muscle weakness (myopathy) in mid-adulthood. However, features of this disease can appear anytime between infancy and late adulthood.[1][2]

Muscle weakness most often begins in the hands and feet (distal muscles), but some people first experience weakness in the muscles near the center of the body (proximal muscles). Facial muscle weakness can rarely cause swallowing and speech difficulties. The muscle weakness is progressive, meaning that it tends to worsen over time.[1]

Other signs and symptoms of MFM can include an enlarged and weakened heart muscle (cardiomyopathy) or an abnormal heart rhythm (arrhythmia), muscle pain (myalgia), and loss of sensation and weakness in the limbs (peripheral neuropathy). For some people, as the disease progresses, the muscles of the lungs may also be affected, which can result in respiratory failure. Individuals with this disease may have skeletal problems including joint stiffness (contractures) and abnormal curvature of the spine (scoliosis). Rarely, people with this disease develop clouding of the front surface of the eyes (cataracts).[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
1%-4% of people have these symptoms
Adult onset
Symptoms begin in adulthood
0003581
Bradycardia
Slow heartbeats
0001662
Dilated cardiomyopathy
Stretched and thinned heart muscle
0001644
Hypertrophic cardiomyopathy
Enlarged and thickened heart muscle
0001639
Respiratory insufficiency due to muscle weakness
Decreased lung function due to weak breathing muscles
0002747
Restrictive cardiomyopathy
0001723
Third degree atrioventricular block
Complete heart block
0001709
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Autosomal recessive inheritance
0000007
Bulbar palsy
0001283
Constipation
0002019
Diarrhea
Watery stool
0002014
Distal muscle weakness
Weakness of outermost muscles
0002460
EMG: myopathic abnormalities
0003458
Facial palsy
Bell's palsy
0010628
Hyporeflexia of lower limbs
0002600
Late-onset proximal muscle weakness
0003694
Neck muscle weakness
Floppy neck
0000467

Cause

Myofibrillar myopathy (MFM) is caused by a mutation (change) in any of several genes, including DESCRYABMYOTLDB3FLNCBAG3FHL1TTNand DNAJB6.[1][3] These genes are all responsible for providing instructions to our bodies to make proteins that help keep our muscles strong. Specifically, the muscles are divided into units called sarcomeres. The proteins that are made by these genes are responsible for linking the sarcomeres together so that they are strong enough to help our bodies move.[2]

When there is a mutation in one of the genes associated with MFM, the muscles are weakened because there is not enough of the linking protein to help make the muscles strong. This causes the symptoms associated with MFM. Because each gene associated with MFM provides instructions for a protein that performs a slightly different function in the muscle, the exact symptoms that are present in each affected individual depends on the exact gene that is changed.[2] There are rare reports of other genes that may be associated with myofibrillar myopathy.[3] In about 50% of people who have MFM, the exact genetic cause of the disease is not identified.[1] This may be because there are other genes that cause MFM that have not yet been discovered.[3]

Diagnosis

Myofibrillar myopathy (MFM) is diagnosed when an individual has signs and symptoms consistent with the disease such as progressive muscle weakness with or without cardiomyopathy. A healthcare professional may want to perform laboratory tests to rule out other causes of progressive muscle weakness. These tests may include:[1] 

  • Electromyography: a study measuring the response of muscles to an electrical stimulus
  • Muscle biopsy: a sample of the muscle is taken to determine how it looks under a microscope
  • Creatine kinase test: a test of an enzyme that can provide information about the health of the muscles

If myofibrillar myopathy is suspected, genetic testing of the genes associated with the disease can be used to confirm the diagnosis and provide more information about long-term outlook.[4]

Treatment

The treatment of myofibrillar myopathy (MFM) depends on the signs and symptoms present in each person. People who have progressive muscles weakness may require physical therapy and assistive devices such as a cane or wheelchair. Individuals who have cardiomyopathy or arrhythmia may require a pacemaker or implantable cardioverter defibrillator (ICD). In severe cases, people with MFM may have progressive heart disease that requires a heart transplant.[1] Surveillance of the heart, lungs, and muscles are recommended every year or as determined by a doctor.

For some affected individuals, the progressive muscle weakness may affect the ability of the muscles of the lungs to work properly, especially at night. This may require respiratory support such as a ventilator to make sure affected individuals are breathing properly.[1]

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.

Organizations Supporting this 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

      • Genetics Home Reference (GHR) contains information on Myofibrillar myopathy. This website is maintained by the National Library of Medicine.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • 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 Myofibrillar myopathy. Click on the link to view a sample search on this topic.

          References

          1. Selcen D and Engel AG. Myofibrillar Myopathy. GeneReviews. October 29, 2012; https://www.ncbi.nlm.nih.gov/books/NBK1499/.
          2. Myofibrillar myopathy. Genetics Home Reference. January 2011; https://ghr.nlm.nih.gov/condition/myofibrillar-myopathy.
          3. Olivé M, Kley RA, and Goldfarb LG. Myofibrillar myopathies: new developments. Current Opinion in Neurology. October 2013; (26)5:527-535. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5127196/.
          4. Connolly AM. Myopathy, Myofibrillar. National Organization for Rare Disorders. 2010; https://rarediseases.org/rare-diseases/myopathy-myofibrillar/.
          5. Ozkaya O. Myofibrillar myopathies. Muscular Dystrophy UK. June 2017; https://www.musculardystrophyuk.org/app/uploads/2016/06/Myofibrillar-myopathy-Final.pdf.

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