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Genetics Home Reference: your guide to understanding genetic conditions
http://ghr.nlm.nih.gov/     A service of the U.S. National Library of Medicine®

Bethlem myopathy

Reviewed October 2010

What is Bethlem myopathy?

Bethlem myopathy is a condition that mainly affects skeletal muscles, which are the muscles used for movement. People with this condition experience progressive muscle weakness and develop joint stiffness (contractures) in their fingers, wrists, elbows, and ankles that can restrict movement. Approximately two-thirds of people with Bethlem myopathy over age 50 will need to use a walker or wheelchair.

The features of Bethlem myopathy can appear at any age. Some individuals have signs of the disorder even before birth, most commonly decreased fetal movement. Other affected individuals develop symptoms soon after birth, including low muscle tone and a stiff neck that causes the head to lean to one side (torticollis). People whose symptoms appear in childhood may experience delayed developmental milestones, such as sitting or walking. Others do not develop features of the condition until late adulthood.

Some people with Bethlem myopathy have skin abnormalities such as small bumps called follicular hyperkeratosis that develop around the elbows and knees; soft, velvety skin of the palms and soles; and wounds that split open with little bleeding and widen over time to create shallow scars.

How common is Bethlem myopathy?

Bethlem myopathy is estimated to occur in 1 in 200,000 individuals.

What genes are related to Bethlem myopathy?

Mutations in the COL6A1, COL6A2, and COL6A3 genes cause Bethlem myopathy. These genes each provide instructions for making one component of a protein called type VI collagen. This protein plays an important role in muscle, particularly skeletal muscle.

Type VI collagen makes up part of the extracellular matrix that surrounds muscle cells. The extracellular matrix is an intricate lattice that forms in the space between cells and provides structural support. The extracellular matrix that surrounds muscle cells is necessary for muscle cell stability and growth.

Mutations in the type VI collagen genes that cause Bethlem myopathy result in the formation of abnormal type VI collagen or reduce the amount of type VI collagen that is produced. A decrease in normal type VI collagen disrupts the extracellular matrix surrounding muscle cells, leading to progressive muscle weakness and the other signs and symptoms of Bethlem myopathy.

Related Gene(s)

Changes in these genes are associated with Bethlem myopathy.

  • COL6A1
  • COL6A2
  • COL6A3

How do people inherit Bethlem myopathy?

Bethlem myopathy is typically inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. Most cases result from new mutations in the gene and occur in people with no history of the disorder in their family. In some cases, an affected person inherits the mutation from one affected parent.

Rarely, this condition 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 condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of Bethlem myopathy?

These resources address the diagnosis or management of Bethlem myopathy and may include treatment providers.

  • Gene Review: Collagen Type VI-Related Disorders (http://www.ncbi.nlm.nih.gov/books/NBK1503)
  • Genetic Testing Registry: Bethlem myopathy (http://www.ncbi.nlm.nih.gov/gtr/conditions/C1834674)
  • Muscular Dystrophy UK: Could Cyclosporine A be used to treat Bethlem myopathy and Ullrich congenital muscular dystrophy? (http://www.musculardystrophyuk.org/news/could-cyclosporine-a-be-used-to-treat-bethlem-myopathy-and-ullrich-congenital-muscular-dystrophy/)

You might also find information on the diagnosis or management of Bethlem myopathy in Educational resources (http://ghr.nlm.nih.gov/condition/bethlem-myopathy/show/Educational+resources) and Patient support (http://ghr.nlm.nih.gov/condition/bethlem-myopathy/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about Bethlem myopathy?

You may find the following resources about Bethlem myopathy helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for Bethlem myopathy?

  • benign congenital muscular dystrophy
  • benign congenital myopathy with contractures

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about Bethlem myopathy?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/gard).

What glossary definitions help with understanding Bethlem myopathy?

autosomal ; autosomal dominant ; autosomal recessive ; benign ; cell ; collagen ; congenital ; extracellular ; extracellular matrix ; gene ; inherited ; joint ; low muscle tone ; muscle cell ; muscle cells ; muscle tone ; muscular dystrophy ; mutation ; protein ; recessive ; skeletal muscle

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).

References

  • Baker NL, Mörgelin M, Pace RA, Peat RA, Adams NE, Gardner RJ, Rowland LP, Miller G, De Jonghe P, Ceulemans B, Hannibal MC, Edwards M, Thompson EM, Jacobson R, Quinlivan RC, Aftimos S, Kornberg AJ, North KN, Bateman JF, Lamandé SR. Molecular consequences of dominant Bethlem myopathy collagen VI mutations. Ann Neurol. 2007 Oct;62(4):390-405. (http://www.ncbi.nlm.nih.gov/pubmed/17886299?dopt=Abstract)
  • Gualandi F, Urciuolo A, Martoni E, Sabatelli P, Squarzoni S, Bovolenta M, Messina S, Mercuri E, Franchella A, Ferlini A, Bonaldo P, Merlini L. Autosomal recessive Bethlem myopathy. Neurology. 2009 Dec 1;73(22):1883-91. doi: 10.1212/WNL.0b013e3181c3fd2a. (http://www.ncbi.nlm.nih.gov/pubmed/19949035?dopt=Abstract)
  • Lampe AK, Bushby KM. Collagen VI related muscle disorders. J Med Genet. 2005 Sep;42(9):673-85. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16141002?dopt=Abstract)
  • Lampe AK, Zou Y, Sudano D, O'Brien KK, Hicks D, Laval SH, Charlton R, Jimenez-Mallebrera C, Zhang RZ, Finkel RS, Tennekoon G, Schreiber G, van der Knaap MS, Marks H, Straub V, Flanigan KM, Chu ML, Muntoni F, Bushby KM, Bönnemann CG. Exon skipping mutations in collagen VI are common and are predictive for severity and inheritance. Hum Mutat. 2008 Jun;29(6):809-22. doi: 10.1002/humu.20704. (http://www.ncbi.nlm.nih.gov/pubmed/18366090?dopt=Abstract)
  • Lucioli S, Giusti B, Mercuri E, Vanegas OC, Lucarini L, Pietroni V, Urtizberea A, Ben Yaou R, de Visser M, van der Kooi AJ, Bönnemann C, Iannaccone ST, Merlini L, Bushby K, Muntoni F, Bertini E, Chu ML, Pepe G. Detection of common and private mutations in the COL6A1 gene of patients with Bethlem myopathy. Neurology. 2005 Jun 14;64(11):1931-7. (http://www.ncbi.nlm.nih.gov/pubmed/15955946?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: October 2010
Published: March 23, 2015