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Disease Profile

Bethlem 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

Infancy

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ICD-10

G71.0

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)

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

Categories

Congenital and Genetic Diseases; Musculoskeletal Diseases; Nervous System Diseases

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 COL6A1COL6A2or 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

Cause

Bethlem myopathy is caused by mutations (changes) in the COL6A1COL6A2or 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]

Genetic testing of the COL6A1COL6A2and 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

      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

        • 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

            1. Collagen VI-related myopathy. Genetics Home Reference (GHR). October 2015; https://ghr.nlm.nih.gov/condition/collagen-vi-related-myopathy.
            2. 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/.
            3. Lamande SR. Collagen Type VI-Related Disorders. National Organization for Rare Disorders. 2015; https://rarediseases.org/rare-diseases/collagen-type-vi-related-disorders/.

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