Myofibrillar myopathy

Rare Endocrinology News

10529

Rare Endocrinology News

Disease Profile

Unknown

US Estimated

Europe Estimated

Age of onset

Adult

ICD-10

G71.8

Inheritance

Myofibrillar myopathy (MFM) can be inherited in a number of different ways depending on the exact gene that is changed. Most cases of MFM are caused by changes in genes that are inherited in an autosomal dominant manner.^[1] This means that only one copy of a gene needs to be changed in order for a person to have signs and symptoms of the disease. We inherit one copy of each gene from our mother and the other one from our father.

In some cases, people with an autosomal dominant form of MFM are the first people in their family who are diagnosed with the disease. This may occur for two reasons. First, it may be that the person diagnosed with the disease is the only person in the family with a genetic change. This means that the genetic change is new (de novo) in the affected individual and it was not inherited from either parent. In other cases, it may be that the parents of the affected individual also have MFM, but they have a form of the disease that is slowly progressing or has not yet been diagnosed. Therefore, if a person is diagnosed with MFM and the exact genetic cause is known, it is important that their parents also receive genetic testing to determine if one of them also has the disease.

MFM can exhibit reduced penetrance and variable expressivity. Reduced penetrance means that some people who have genetic changes that cause MFM may not have signs or symptoms of the disease. However, these people can still pass on MFM to their children. Variable expressivity means that the exact symptoms of each person with MFM can differ, even within the same family. For example, some affected individuals may have both cardiomyopathy and muscle weakness, while others may just have one or the other.^[1]

If MFM is caused by a change in the FHL1 gene, it is inherited in an X-linked manner.^[1] This means that the FHL1 gene is located on the X chromosome. The X chromosome is one of the sex chromosomes. Each woman has two X chromosomes, and each man has one X chromosome and one Y chromosome. Because men have only one X chromosome, they only have one copy of the FHL1 gene. If this gene has a mutation, they will have MFM. However, women who have changes in one copy of the FHL1 gene are known as carriers of the disease. Most carriers do not have signs or symptoms of MFM because they have another working copy of FHL1.

If MFM is caused by a change in CRYAB, it is inherited in an autosomal recessive manner.^[1] This means that both copies of the CRYAB gene must be changed in order to have symptoms of the disease. Men and women with a mutation in only one copy of the CRYAB gene are known as carriers, meaning they do not have signs or symptoms of the disease. When two carriers of a CRYAB mutation have children together, for each child there is a:

25% chance that the child will have MFM
50% chance that the child will be a carrier of MFM like the parents
25% chance that the child will have two working copies of CRYAB, so the child will not have MFM and will not be a carrier.

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

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.

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.

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

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.

Not applicable

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 DES, CRYAB, MYOT, LDB3, FLNC, BAG3, FHL1, TTN, and 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

Do you have updated information on this disease? We want to hear from you.

Cause

Myofibrillar myopathy (MFM) is caused by a mutation (change) in any of several genes, including DES, CRYAB, MYOT, LDB3, FLNC, BAG3, FHL1, TTN, and 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

Cardiomyopathy Association
Chiltern Court
Asheridge Road
Unit 10
Chesham Buckinghamshire HP5 2PX
United Kingdom
Telephone: +44 01494 791 224
Fax: +44 1923 249 987
E-mail: contact@cardiomyopathy.org
Website: https://www.cardiomyopathy.org
Children's Cardiomyopathy Foundation
P.O. Box 547
Tenafly, NJ 07670
Toll-free: 866-808-CURE (2873)
Fax: 201-227-7016
E-mail: info@childrenscardiomyopathy.org
Website: https://www.childrenscardiomyopathy.org/

Social Networking Websites

Myofibrillar Myopathy Facebook Support Group
Website: https://www.facebook.com/groups/880994568701030/

Organizations Providing General Support

Muscular Dystrophy Association (MDA)
222 S Riverside Plaza
Suite 1500
Chicago, IL 60606
Toll-free: 1-833-275-6321 (Helpline)
E-mail: resourcecenter@mdausa.org
Website: https://www.mda.org

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

Selcen D and Engel AG. Myofibrillar Myopathy. GeneReviews. October 29, 2012; https://www.ncbi.nlm.nih.gov/books/NBK1499/.
Myofibrillar myopathy. Genetics Home Reference. January 2011; https://ghr.nlm.nih.gov/condition/myofibrillar-myopathy.
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/.
Connolly AM. Myopathy, Myofibrillar. National Organization for Rare Disorders. 2010; https://rarediseases.org/rare-diseases/myopathy-myofibrillar/.
Ozkaya O. Myofibrillar myopathies. Muscular Dystrophy UK. June 2017; https://www.musculardystrophyuk.org/app/uploads/2016/06/Myofibrillar-myopathy-Final.pdf.

Rare Endocrinology News

Rare Endocrinology News

Rare Endocrinology News

Adult

G71.8

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

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.

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.

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

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.

Not applicable

Other names (AKA)

Summary

Symptoms

Cause

Diagnosis

Treatment

Organizations

Organizations Supporting this Disease

Social Networking Websites

Organizations Providing General Support

Learn more

Where to Start

In-Depth Information

References

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.

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