Bethlem myopathy

Rare Pediatrics News

873

Rare Pediatrics News

Disease Profile

Bethlem myopathy

<1 / 1 000 000

US Estimated

Europe Estimated

Age of onset

Infancy

ICD-10

G71.0

Inheritance

Bethlem myopathy is typically inherited in an autosomal dominant manner, meaning one copy of the altered gene in each cell is sufficient to cause the disease.^[1] We inherit one copy of each of our genes from our mother and the other from our father. Many cases of Bethlem myopathy result from new (de novo) mutations in the gene, meaning the mutations were not inherited from either parent. When people who have a new mutation in a gene causing Bethlem myopathy go on to have children, each of their children will have a 50% chance of inheriting the disease.

In some cases, a person who has Bethlem myopathy inherited the mutation from one affected parent. In these cases, future children of this parent will also have a 50% chance to inherit the disease. The parent who has the disease may be so mildly affected that they didn’t know they were showing symptoms of the disease at all.

In rare cases, Bethlem myopathy is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive disease each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the disease.^[1]^[2] These individuals are known as carriers. When two carriers of a gene mutation causing Bethlem myopathy have children, for each child there is a:

25% chance that the child will have Bethlem myopathy
50% chance that the child will be a carrier of Bethlem myopathy like the parents
25% chance that the child will have two working copies of the gene that makes type VI collagen, so the child will not have Bethlem myopathy 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)

Myopathy, benign congenital, with contractures; Muscular dystrophy, benign congenital

Summary

Bethlem myopathy is a rare disease affecting the skeletal muscles and connective tissue. The disease is characterized by slowly progressive muscle weakness and joint stiffness (contractures). It most often affects the fingers, wrists, elbows, and ankles.^[1]^[2] Signs and symptoms may begin before birth (with decreased fetal movements), shortly after birth (with low muscle tone or torticollis), in early childhood (with delayed motor skills, muscle weakness, and contractures), or in adulthood (with weakness, Achilles tendon, or finger contractures). Due to the disease's progression, most people with Bethlem myopathy over age 50 require mobility aids (such as a cane, crutches, or wheelchair) for outdoor mobility. Rarely, severe muscle weakness may lead to respiratory difficulties in later life.^[2]

Bethlem myopathy is caused by mutations (changes) in the COL6A1, COL6A2, or COL6A3 genes. Most cases are inherited in an autosomal dominant manner, but in rare cases the disease is autosomal recessive.^[1]^[2] The diagnosis is based on clinical examination and laboratory tests, but genetic testing may confirm the diagnosis.^[2] Treatment depends on individual symptoms but routinely involves physical therapy. Surgery to correct joint contractures may be needed.^[2]

Symptoms

Bethlem myopathy mainly affects skeletal muscles, which are the muscles used for movement. People with this disease experience progressive muscle weakness and joint stiffness (contractures) in their fingers, wrists, elbows, and ankles. The features of Bethlem myopathy can appear at any age. In some cases, the symptoms start before birth with decreased fetal movements. In others, low muscle tone (hypotonia) and a stiff neck (torticollis) develop during infancy. During childhood, developmental delay may be noted. For example a baby with Bethlem myopahy may learn to sit by themselves or walk later than usual. In some, symptoms don’t occur until adulthood, when a person may notice muscle weakness. By the age of 50-years-old, approximately two-thirds (66%) of people with Bethlem myopathy will need to use a walker, cane, or wheelchair.^[1]^[2]

In addition to the muscle problems, some people with Bethlem myopathy have skin abnormalities. These abnormalities may include small bumps called follicular hyperkeratosis that develop around the elbows and knees or soft, velvety skin on the palms and soles. Some people may also have wounds that split open with little bleeding and widen over time to create shallow scars.^[1] Rarely, individuals with Bethlem myopathy may develop breathing problems as the disease progresses.^[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
80%-99% of people have these symptoms
Cachexia	Wasting syndrome	0004326
Camptodactyly of finger	Permanent flexion of the finger	0100490
EMG abnormality		0003457
Joint stiffness	Stiff joint Stiff joints [ more ]	0001387
Progressive proximal muscle weakness		0009073
30%-79% of people have these symptoms
Ankle flexion contracture		0006466
Joint laxity	Joint instability Lax joints Loose-jointedness Loosejointedness [ more ]	0001388
Multiple joint contractures		0002828
Muscular dystrophy		0003560
Neonatal hypotonia	Low muscle tone, in neonatal onset	0001319
Proximal amyotrophy	Wasting of muscles near the body	0007126
Torticollis	Wry neck	0000473
5%-29% of people have these symptoms
Follicular hyperkeratosis		0007502
Percent of people who have these symptoms is not available through HPO
Abnormality of the cardiovascular system	Cardiovascular abnormality	0001626
Autosomal dominant inheritance		0000006
Autosomal recessive inheritance		0000007
Congenital muscular torticollis		0005988
Decreased fetal movement	Less than 10 fetal movements in 12 hours	0001558
Distal muscle weakness	Weakness of outermost muscles	0002460
Elbow flexion contracture	Contractures of elbows Elbow contracture Elbow contractures [ more ]	0002987
Elevated serum creatine kinase	Elevated blood creatine phosphokinase Elevated circulating creatine phosphokinase Elevated creatine kinase Elevated serum CPK Elevated serum creatine phosphokinase High serum creatine kinase Increased CPK Increased creatine kinase Increased creatine phosphokinase Increased serum CK Increased serum creatine kinase Increased serum creatine phosphokinase [ more ]	0003236
Limb-girdle muscle weakness		0003325
Motor delay		0001270
Myopathy	Muscle tissue disease	0003198
Proximal muscle weakness	Weakness in muscles of upper arms and upper legs	0003701
Respiratory insufficiency due to muscle weakness	Decreased lung function due to weak breathing muscles	0002747
Skeletal muscle atrophy	Muscle degeneration Muscle wasting [ more ]	0003202
Slow progression	Signs and symptoms worsen slowly with time	0003677
Variable expressivity		0003828

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

Cause

Bethlem myopathy is caused by mutations (changes) in the COL6A1, COL6A2, or COL6A3 genes. These genes each provide instructions for making one component of a protein called type VI collagen. This protein plays an important role in the muscles, particularly skeletal muscles. Type VI collagen makes up part of the extracellular matrix, an intricate lattice that forms in the space between cells and provides structural support to the muscles.^[1]

Mutations in the type VI collagen genes result in the formation of abnormal type VI collagen or reduced amounts of type VI collagen. This decrease in amounts of normal type VI collagen disrupts the extracellular matrix surrounding muscle cells, which leads to the progressive muscle weakness and other signs and symptoms of Bethlem myopathy.^[1]

Diagnosis

Bethlem myopathy is typically diagnosed based on a clinical evaluation that identifies signs and symptoms typical of people with the disease. A healthcare provider may recommend additional laboratory test including:^[2]^[3]

Blood test measuring creatine kinase (CK) levels: these levels will typically be normal or only slightly elevated
Skin biopsy
Muscle MRI
Electromyography (EMG)

Genetic testing of the COL6A1, COL6A2, and COL6A3 genes can confirm the diagnosis.

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

Treatment for Bethlem myopathy is symptomatic and supportive. This means that treatment aims to relieve symptoms and improve quality of life. There is currently no cure for the disease, and there are no specific medications for Bethlem myopathy. In many cases, physical therapy, stretching exercises, braces, splints, and mobility aids such as a walker or wheelchair are helpful. In rare cases, surgery may be needed to help with joint contractures or scoliosis.^[2]

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

Cure CMD Congenital Muscular Dystrophy
19401 S. Vermont Ave., Suite J100
Torrance, CA 90502
Telephone: 323-250-2399 or 424-265-0874
E-mail: info@curecmd.org
Website: https://www.curecmd.org/

Social Networking Websites

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
Muscular Dystrophy UK
61A Great Suffolk Street
London, SE1 0BU United Kingdom
Toll-free: 0800 652 6352 (Helpline)
Telephone: (+44) 0 020 7803 4800
E-mail: info@musculardystrophyuk.org
Website: https://www.musculardystrophyuk.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

MedlinePlus Genetics contains information on Bethlem 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.
The Muscular Dystrophy Association has developed a resource called "Facts About Myopathies" that discusses commonly asked questions regarding myopathies. Click on the link above to view this information page.

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 Bethlem myopathy. Click on the link to view a sample search on this topic.

References

Collagen VI-related myopathy. Genetics Home Reference (GHR). October 2015; https://ghr.nlm.nih.gov/condition/collagen-vi-related-myopathy.
Lampe AK, Flanigan KM, Bushby KM, Hicks D. Collagen Type VI-Related Disorders. GeneReviews. August 9, 2012; https://www.ncbi.nlm.nih.gov/books/NBK1503/.
Lamande SR. Collagen Type VI-Related Disorders. National Organization for Rare Disorders. 2015; https://rarediseases.org/rare-diseases/collagen-type-vi-related-disorders/.

Rare Pediatrics News

Rare Pediatrics News

Rare Pediatrics News

Infancy

G71.0

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)

Categories

Summary

Symptoms

Cause

Diagnosis

Testing Resources

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.