Bethlem myopathy

Last updated
Bethlem myopathy
Autosomal dominant - en.svg
Bethlem myopathy has an autosomal dominant pattern of inheritance (autosomal recessive form exists as well [1] )

Bethlem myopathy is an autosomal dominant myopathy, classified as a congenital form of muscular dystrophy, that is caused by a mutation in one of the three genes coding for type VI collagen. [2] These include COL6A1, COL6A2, and COL6A3. [3] Gower's sign, tiptoe-walking and contractures of the joints (especially the fingers) are typical signs and symptoms of the disease. Bethlem myopathy could be diagnosed based on clinical examinations and laboratory tests may be recommended. Currently there is no cure for the disease and symptomatic treatment is used to relieve symptoms and improve quality of life. Bethlem myopathy affects about 1 in 200,000 people. [4]

Contents

Signs and symptoms

The onset of this disease can begin even before birth but is more commonly in childhood or later into adult life. The progression is slow, with symptoms of weakness and walking difficulties sometimes not presenting until middle age. Early symptoms include Gower's sign ("climbing" up the thighs with the hands when rising from the floor) and tiptoe-walking caused by the beginning of contractures.[ citation needed ]

Contractures of the fingers are a typical symptom of Bethlem myopathy but not of the related Ullrich's myopathy (which does include contractures of arms and legs, as does Bethlem myopathy). Serum creatine kinase is elevated in Bethlem myopathy, as there is ongoing muscle cell death. Patients with Bethlem myopathy may expect a normal life span and continued mobility into adulthood.[ citation needed ]

Diagnosis

The disease could be diagnosed based on a clinical examination, which identifies signs and symptoms generally associated with the people who have the condition. Additional laboratory tests may be recommended. Creatine kinase (CK) blood test results will generally be normal or only slightly elevated. Skin biopsy, MRI of the muscles, electromyography (EMG) are the main testing methods of the disease. The diagnosis can be confirmed with genetic testing of the COL6A1, COL6A2, and COL6A3 genes. [5]

Phenotypes of overlap between Ullrich congenital muscular dystrophy (UCMD) and Bethlem can be assumed. In the differential diagnosis of UCDM, even in patients without finger contractures, Bethlem myopathy could be considered. [6]

Treatment

Currently there is no cure for the disease. Symptomatic treatment, which aims to relieve symptoms and improve quality of life is the main treatment method of Bethlem myopathy. It is believed that physical therapy, stretching exercises, orthoses such as braces and splints, and mobility aids like a walker or wheelchair are beneficial to patient's condition. [5]

Surgical options could be considered in rare instances, in order to help with joint contractures or scoliosis. [5] Contractures of the legs can be alleviated with heel-cord surgery followed by bracing and regular physical therapy. Repeated surgeries to lengthen the heel cords may be needed as the child grows to adulthood. [2]

Epidemiology

According to a Japanese study from 2007 Bethlem myopathy affects about 1 in 200,000 people. [4] A 2009 study concerning the prevalence of genetic muscle disease in Northern England estimated the prevalence of Bethlem myopathy to be at 0.77:100,000. [7] Together with the UCMD it is believed to be underdiagnosed. Both conditions have been described in individuals from a variety of ethnic backgrounds. [8]

Related Research Articles

Arthrogryposis Medical condition

Arthrogryposis, describes congenital joint contracture in two or more areas of the body. It derives its name from Greek, literally meaning "curving of joints".

Duchenne muscular dystrophy Type of muscular dystrophy

Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy that primarily affects boys. Muscle weakness usually begins around the age of four, and worsens quickly. Muscle loss typically occurs first in the thighs and pelvis followed by the arms. This can result in trouble standing up. Most are unable to walk by the age of 12. Affected muscles may look larger due to increased fat content. Scoliosis is also common. Some may have intellectual disability. Females with a single copy of the defective gene may show mild symptoms.

Becker muscular dystrophy X-linked recessive inherited disorder characterized by slowly progressive muscle weakness of the legs and pelvis

Becker muscular dystrophy is an X-linked recessive inherited disorder characterized by slowly progressing muscle weakness of the legs and pelvis. It is a type of dystrophinopathy. This is caused by mutations in the dystrophin gene, which encodes the protein dystrophin. Becker muscular dystrophy is related to Duchenne muscular dystrophy in that both result from a mutation in the dystrophin gene, but has a milder course.

Fukuyama congenital muscular dystrophy Medical condition

Fukuyama congenital muscular dystrophy (FCMD) is a rare, autosomal recessive form of muscular dystrophy mainly described in Japan but also identified in Turkish and Ashkenazi Jewish patients; fifteen cases were first described on 1960 by Dr. Yukio Fukuyama.

In medicine, myopathy is a disease of the muscle in which the muscle fibers do not function properly. This results in muscular weakness. Myopathy means muscle disease. This meaning implies that the primary defect is within the muscle, as opposed to the nerves or elsewhere. Muscle cramps, stiffness, and spasm can also be associated with myopathy.

Hereditary inclusion body myopathies (HIBM) are a group of rare genetic disorders which have different symptoms. Generally, they are neuromuscular disorders characterized by muscle weakness developing in young adults. Hereditary inclusion body myopathies comprise both autosomal recessive and autosomal dominant muscle disorders that have a variable expression (phenotype) in individuals, but all share similar structural features in the muscles.

Congenital muscular dystrophy Medical condition

Congenital muscular dystrophies are autosomal recessively-inherited muscle diseases. They are a group of heterogeneous disorders characterized by muscle weakness which is present at birth and the different changes on muscle biopsy that ranges from myopathic to overtly dystrophic due to the age at which the biopsy takes place.

Myotonic dystrophy Genetic disorder that impairs muscle function

Myotonic dystrophy (DM) is a type of muscular dystrophy, a group of long-term genetic disorders that cause progressive muscle loss and weakness. In myotonic dystrophy, muscles are often unable to relax after contraction. Other symptoms may include cataracts, intellectual disability and heart conduction problems. In men, there may be early balding and an inability to have children. While myotonic dystrophy can occur at any age, onset is typically in the 20s and 30s.

Congenital myopathy is a very broad term for any muscle disorder present at birth. This defect primarily affects skeletal muscle fibres and causes muscular weakness and/or hypotonia. Congenital myopathies account for one of the top neuromuscular disorders in the world today, comprising approximately 6 in 100,000 live births every year. As a whole, congenital myopathies can be broadly classified as follows:

NIM811 Chemical compound

NIM811 is a mitochondrial permeability transition inhibitor. Also known as N-methyl-4-isoleucine cyclosporin, it is a four-substituted cyclosporine analogue that binds to cyclophilin, however this binary complex cannot bind to calcineurin, and therefore lacks immunosuppressive activity.

Collagen, type VI, alpha 1

Collagen alpha-1(VI) chain is a protein that in humans is encoded by the COL6A1 gene.

Collagen, type VI, alpha 2

Collagen alpha-2(VI) chain is a protein that in humans is encoded by the COL6A2 gene.

Collagen, type VI, alpha 3

Collagen alpha-3(VI) chain is a protein that in humans is encoded by the COL6A3 gene. This protein is an alpha chain of type VI collagen that aids in microfibril formation. As part of type VI collagen, this protein has been implicated in Bethlem myopathy, Ullrich congenital muscular dystrophy (UCMD), and other diseases related to muscle and connective tissue.

Central core disease Medical condition

Central core disease (CCD), also known as central core myopathy, is an autosomal dominantly inherited muscle disorder present from birth that negatively affects the skeletal muscles. It was first described by Shy and Magee in 1956. It is characterized by the appearance of the myofibril under the microscope.

Marden–Walker syndrome Medical condition

Marden–Walker syndrome (MWS) is a rare autosomal recessive congenital disorder. It is characterized by blepharophimosis, microcephaly, micrognathia, multiple joint contractures, arachnodactyly, camptodactyly, kyphoscoliosis and delayed motor development and is often associated with cystic dysplastic kidneys, dextrocardia, Dandy–Walker malformation and agenesis of corpus callosum.

Ullrich congenital muscular dystrophy Medical condition

Ullrich congenital muscular dystrophy is a form of congenital muscular dystrophy. It is associated with variants of type VI collagen, it is commonly associated with muscle weakness and respiratory problems, though cardiac issues are not associated with this type of CMD. It is named after Otto Ullrich, who is also known for the Ullrich-Turner syndrome.

Collagen VI (ColVI) is a type of collagen primarily associated with the extracellular matrix of skeletal muscle. ColVI maintains regularity in muscle function and stabilizes the cell membrane. It is synthesized by a complex, multistep pathway that leads to the formation of a unique network of linked microfilaments located in the extracellular matrix (ECM). ColVI plays a vital role in numerous cell types, including chondrocytes, neurons, myocytes, fibroblasts, and cardiomyocytes. ColVI molecules are made up of three alpha chains: α1(VI), α2(VI), and α3(VI). It is encoded by 6 genes: COL6A1, COL6A2, COL6A3, COL6A4, COL6A5, and COL6A6. The chain lengths of α1(VI) and α2(VI) are about 1,000 amino acids. The chain length of α3(VI) is roughly a third larger than those of α1(VI) and α2(VI), and it consists of several spliced variants within the range of 2,500 to 3,100 amino acids.

Camptocormia

Camptocormia, also known as bent spine syndrome (BSS), is a symptom of a multitude of diseases that is most commonly seen in the elderly. It is identified by an abnormal thoracolumbar spinal flexion, which is a forward bending of the lower joints of the spine, occurring in a standing position. In order to be classified as BSS, the anterior flexion must be of 45 degrees anteriorly. This classification differentiates it from a similar syndrome known as kyphosis. Although camptocormia is a symptom of many diseases, there are two common origins: neurological and muscular. Camptocormia is treated by alleviating the underlying condition causing it through therapeutic measures or lifestyle changes.

Muscle–eye–brain disease Medical condition

Muscle–eye–brain (MEB) disease, also known as muscular dystrophy-dystroglycanopathy congenital with brain and eye anomalies A3 (MDDGA3), is a kind of rare congenital muscular dystrophy (CMD), largely characterized by hypotonia at birth. Patients suffer from muscular dystrophy, central nervous system abnormalities and ocular abnormalities, the condition is degenerative.

Calpainopathy Medical condition

Calpainopathy is the most common type of autosomal recessive limb-girdle muscular dystrophy (LGMD). It preferentially affects the muscles of the hip girdle and shoulder girdle.

References

  1. RESERVED, INSERM US14 -- ALL RIGHTS. "Orphanet: Bethlem myopathy". www.orpha.net. Retrieved 23 December 2017.
  2. 1 2 Jobsis GJ, Boers JM, Barth PG, de Visser M (1999). "Bethlem myopathy: a slowly-progressive congenital muscular dystrophy with contractures". Brain. 122 (4): 649–655. doi: 10.1093/brain/122.4.649 . PMID   10219778.
  3. Lampe AK, Bushby KM (September 2005). "Collagen VI related muscle disorders". J. Med. Genet. 42 (9): 673–85. doi:10.1136/jmg.2002.002311. PMC   1736127 . PMID   16141002.
  4. 1 2 Okada M et al (2007) Primary collagen VI deficiency is the second most common congenital muscular dystrophy in Japan. Neurolog 69:1035–1042
  5. 1 2 3 "Bethlem myopathy | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 2020-10-19.
  6. Reed, Umbertina Conti; Ferreira, Lucio Gobbo; Liu, Enna Cristina; Resende, Maria Bernadete Dutra; Carvalho, Mary Souza; Marie, Suely Kazue; Scaff, Milberto (September 2005). "Ullrich congenital muscular dystrophy and bethlem myopathy: clinical and genetic heterogeneity". Arquivos de Neuro-Psiquiatria. 63 (3B): 785–790. doi: 10.1590/S0004-282X2005000500013 . ISSN   0004-282X.
  7. Norwood, Fiona L. M.; Harling, Chris; Chinnery, Patrick F.; Eagle, Michelle; Bushby, Kate; Straub, Volker (2009). "Prevalence of genetic muscle disease in Northern England: in-depth analysis of a muscle clinic population". Brain: A Journal of Neurology. 132 (Pt 11): 3175–3186. doi:10.1093/brain/awp236. ISSN   1460-2156. PMC   4038491 . PMID   19767415.
  8. Lampe, Anne Katrin; Flanigan, Kevin M.; Bushby, Katharine Mary; Hicks, Debbie (1993), Adam, Margaret P.; Ardinger, Holly H.; Pagon, Roberta A.; Wallace, Stephanie E. (eds.), "Collagen Type VI-Related Disorders", GeneReviews®, Seattle (WA): University of Washington, Seattle, PMID   20301676 , retrieved 2020-10-19
Classification
D
External resources