Congenital myopathy

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Congenital Myopathy
Classification and external resources
ICD-10 G71.2
ICD-9 359.0
eMedicine article/1175852
MeSH D020914

Congenital myopathy is a term for any muscle disorder present at birth. This defect of either the brain, stimulating nerve, or muscle causes weakness throughout the skeletal muscle.[1] Congenital myopathies account for one of the top neuromuscular disorders in the world today, comprising approximately 6 in 100,000 live births every year.[2] Congenital myopathies can broadly be defined as follows:[3]

  • An obvious abnormality in the skeletal muscle on the cellular level; observable via electron or light microscope
  • Originates in the myofibrae, affecting the sarcolemma, or skeletal muscle cell membrane.
  • Symptoms of muscle weakness and hypotonia
  • Is a congenital disorder, meaning it occurs during development and symptoms present themselves at birth or in early life.
  • Is a genetic disorder.

Impairments in Embryological Development[edit]

Skeletal muscle develops from the myotome and dermamyotome derivatives.[4] Since there is such variation between different types of congenital myopathies, the processes of disease onset is also quite varied. Below is a brief explanation for some of the major groupings of congenital myopathies.

Myopathies with Protein Accumulation[edit]

Development of congenital myopathies with protein accumulation is one of the best understood, as the most understood congenital myopathy, nemaline myopathy (see below) falls into this category. Typically, the development error in this category occurs with the genes coding for the thin filaments of the sarcomere and the genes coding for the proteins responsible for replacing thin filaments. Currently, this is how scientists believe protein accumulation begins. Since the proteins involved in building and turnover of the sarcomere no longer function, sarcomere components build up within the cell, slowing contraction and causing weakness of the skeletal muscles.[3]

Myopathies with Cores[edit]

Myopathies with cores, such as multicore and central core myopathies discussed below, are due to mutation in the genes that code for involved in calcium regulation. Calcium is a major component in excitation-contraction coupling, which is the basic process of muscle contraction. This error causes malfunctioning of the sarcoplasmic recticulum, which releases calcium, and the calcium regulatory gates within the muscle. Malfunctions in both of these areas can lead to lower levels of calcium within the muscle, causing the muscle weakness.[3]

Myopathies with Central Nuclei[edit]

Myopathies with central nuclei, such as myotubular myopathy, involves an error in the gene involved in vesicle movement throughout the cell. This creates problems in vesicles reaching the plasma membrane with the cellular components necessary to fuse myoblast, a major step in the formation of the skeletal muscle. This creates structural problems throughout the skeletal muscle and in the Z line of the sarcomere, creating the weakness in the muscle.[3]

Myopathies with Fiber Size Variation[edit]

Myopathies with varying fiber size, such as congenital fiber type disproportion, occurs when type 1 fibers, the slow twitch fibers involved in sustaining activity, are smaller than type 2 fibers, the fast twitch fibers involved in quick activity. Since smaller type 1 fibers is not associated with nemaline myopathy, the most common type of congenital myopathy, it has not been studied in as great detail as many of the others. However, the smaller type 1 fibers explains why patients typically can participate in activities for shorter periods of time, but struggle with extended activity.[3]

Types[edit]

The conditions included under the term "congenital myopathy" can vary. One source includes nemaline myopathy, myotubular myopathy, central core myopathy, congenital fiber type disproportion, and multicore myopathy.[5] The term can also be used more broadly, to describe conditions present from birth.

Nemaline myopathy[edit]

Nemaline myopathy is skeletal muscle weakness typically in the face, neck, and limb regions. Approximately 1 in 50,000 people are affected by this disorder. Today, at least six gene mutations are known to cause nemaline myopathy. All the genes are involved in protein production of the sacromere, the main unit of muscle contraction within skeletal muscle. Histologically, protein accumulation can be seen within cells of affected skeletal muscles. Nemaline myopathy is an autosomal recessive genetic disorder, meaning mutated copies must be inherited from both parents for the disease to onset.[6]

Myotubular myopathy[edit]

Myotubular myopathy, also known as centeronuclear myopathy, is recognized by pain during exercise and difficulty walking. People affected by this disease typically are wheel-chair-bound by middle adulthood, have weakness in the muscles involved in eye movement, nerve function disorders, and some form of intellectual disability. Myotubular myopathy is very rare, with less than 50 families currently affected. Genetically, myotubular myopathy can have two causes: autosomal dominant and autosomal recessive. When caused by a mutation in the DNM2 gene, the disorder is autosomal dominant, meaning it can be passed on by one mutated gene. When the mutation takes place in the BIN1 gene, the disease is instead autosomal recessive, and both genes must be mutated for the disease to be inherited. Autosomal recessive oset is most common.[7]

Central core myopathy[edit]

Central core myopathy is mild weakness in skeletal muscle that persists throughout life but typically does not worsen with time. People with central core disease typically have poor reactions to surgeries and some medications, which require the use of muscle relaxants.[8] Central core myopathy is believed to be more prevalent than currently reported, as it is hard to recognize and often misdiagnosed in early childhood.[2] Central core myopathy has been found to strongly relate to malignant hyperthermia, which strongly increases metabolic activities in the body to leading to potential circulatory system collapse. Mutations typically appear in the RYR1 gene.[2]

Congenital fiber type disproportion[edit]

Congenital fiber type disproportion affects skeletal muscle, typically causing weakness in the shoulders, upper arms, thighs, and hips. Skeletal muscle is made up of two kinds of fiber, type 1 and type 2. In congenital fiber type disproportion, type 1 fibers are not only smaller but often more abundant than type 2 fibers.[9] This leads to affected individuals being able to maintain an active lifestyle, though they usually have lower levels of stamina.[10] Severity with this disease varies greatly, but people typically present symptoms by the age of one. Individuals do not usually worsen with time, and cases have even been reported of improvements.[10]

Multicore myopathy[edit]

Multicore myopathy, also referred to as minicore myopathy, is associated with small areas of decreased oxidative activities, resulting in areas that appear in this histology as “cores”. These appear through microscopy very similar to central core, however the cores are typically smaller in multicore myopathy. As with congenital fiber type disproportion, patients have a greater number of type 1 fibers. Overall, approximately half of diagnosed individuals report no progression of muscle weakness, while half report a very slow progression.[11]

Cylindrical spiral myopathy[edit]

Cylindrical spiral myopathy is very rare with only 18 individual cases described as of 2013. The majority of cases are sporadic, and has been observed in only 3 families. It is characterized by the presence of cylindrical spirals(CS) as the main pathologic finding, which are unusual spiraling lamellar structures seen during electron microscopic examination of skeletal muscle from the affected patient. These structures appear to merge into tubular structures strongly resembling tubular aggregates. Tubular aggregates have been observed in various muscle disorders and appear as densely packed tubules. Cylindrical spirals were first described in 1979.[12] The genetics underlying cylindrical spiral myopathy are currently entirely unknown. A mutation affecting the sarcoplasmic reticulum seems likely, as SERCA1 antibodies have been shown to bind to cylindrical spirals,[13] and the spirals appear to merge into tubular aggregates. Tubular aggregates have been proven to arise from the sarcoplasmic reticulum.[14]

Phenotypes are quite variable, and manifestations can include weakness, abnormal gait, scoliosis, myotonia, cramps, and scoliosis.[15][16][17]

Diagnosis[edit]

There are a variety of tests physicians can run to determine if a person is inflicted with one of the myopathy types. Tests can be run to check creatine kinase levels in the blood, or electromyography can be run to check the electrical activity of the muscle. However, diagnosis heavily relies on muscle pathology, where physician view the muscle on the cellular level. Diagnosis usually relies on this method, as creatine kinase levels and electromyography can come back normal even in inflicted patients.[1] Since congenital myopathy does occur during the development of the embryo, there have also been some advancements in prenatal screenings for the disease.[3]

Treatment[edit]

Currently, there are no treatments for any of the congenital myopathies types. However, depending on the severity, there are different therapies available to help alleviate any pain and aid patients in performing varying activities. For example, many congenital myopathy patients are involved in physical or occupational therapy in an attempt to strengthen their skeletal muscles. In certain cases, orthopedic surgery may be an option, especially with myopathies affected the pectoral and pelvic girdles. Survival is typically determined by the level of respiratory muscle insufficiency.[3]

References[edit]

  1. ^ a b "Congenital Myopathy Information Page". National Institute of Neurological Disorders and Stroke. September 30, 2011. 
  2. ^ a b c Jungbluth, Heinz (2007). "Central core disease". Orphanet Journal of Rare Diseases 2: 25. doi:10.1186/1750-1172-2-25. PMC 1887524. PMID 17504518. 
  3. ^ a b c d e f g North, Kathryn (2008). "What's new in congenital myopathies?". Neuromuscular Disorders 18 (6): 433–42. doi:10.1016/j.nmd.2008.04.002. PMID 18482838. 
  4. ^ Musculo-skeletal system. (n.d.). Retrieved from http://vanat.cvm.umn.edu/TFFlectPDFs/LectMusculoSkeletal%20Devel.pdf[page needed][unreliable medical source?]
  5. ^ Rubin, M. (2009, August). Congenital myopathies. Retrieved from http://www.merckmanuals.com/professional/pediatrics/inherited_muscular_disorders/congenital_myopathies.html?qt=&sc=&alt=
  6. ^ Nemaline myopathy. (2012, November 25). Retrieved from http://ghr.nlm.nih.gov/condition/nemaline-myopathy
  7. ^ Centronuclear myopathy. (2012, November 25). Retrieved from http://ghr.nlm.nih.gov/condition/centronuclear-myopathy
  8. ^ "Central core disease - Genetics Home Reference". Ghr.nlm.nih.gov. 2013-09-23. Retrieved 2013-10-06. 
  9. ^ Fibre-type disproporion. (2012). Retrieved from http://www.muscular-dystrophy.org/about_muscular_dystrophy/conditions/115_fibre-type_disproportion
  10. ^ a b "Congenital fiber-type disproportion". Genetics Home Reference. U.S. National Library of Medicine. December 2, 2012. 
  11. ^ Myong, NH; Kang, YK; Chi, JG; Suk, SI (1993). "Multicore myopathy--a case report". Journal of Korean medical science 8 (4): 312–7. PMC 3053753. PMID 8198769. 
  12. ^ Cylindrical spirals in human skeletal muscle. http://www.ncbi.nlm.nih.gov/pubmed/492204
  13. ^ http://www.nmd-journal.com/article/S0960-8966(98)00098-4/fulltext
  14. ^ Tubular aggregates are from whole sarcoplasmic reticulum origin: alterations in calcium binding protein expression in mouse skeletal muscle during aging. http://www.ncbi.nlm.nih.gov/pubmed/15036331
  15. ^ Cylindrical Spirals Congenital Myopathy Associated with Epileptic Encephalopathy http://www.neurology.org/cgi/content/meeting_abstract/80/1_MeetingAbstracts/P07.050
  16. ^ Cylindrical spirals in a familial neuromuscular disorder. http://www.ncbi.nlm.nih.gov/pubmed/7436360
  17. ^ Autosomal dominant neuromuscular disease with cylindrical spirals. http://www.ncbi.nlm.nih.gov/pubmed/1822355

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