Myotonia
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Myotonia | |
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Specialty | Neurology, neuromuscular medicine, medical genetics |
Myotonia is a symptom of a small handful of certain
Myotonia is the defining symptom of many channelopathies (diseases of ion channel transport) such as myotonia congenita, paramyotonia congenita and myotonic dystrophy.[3][4]
Generally, repeated contraction of the muscle can alleviate the myotonia and relax the muscles thus improving the condition, however, this is not the case in paramyotonia congenita. This phenomenon is known as the "warm-up" reflex[8] and is not to be confused with warming up before exercise, though they may appear similar. Individuals with the disorder may have trouble releasing their grip on objects or may have difficulty rising from a sitting position and a stiff, awkward gait.
Myotonia can affect all muscle groups; however, the pattern of affected muscles can vary depending on the specific disorder involved.
People with disorders involving myotonia can have life-threatening reactions to certain
Causes
Myotonia may present in the following diseases, with different causes related to the ion channels in the skeletal muscle fiber membrane (sarcolemma).[citation needed]
Myotonic dystrophy
Two documented types, DM1 and DM2 exist. In myotonic dystrophy a nucleotide expansion of either of two genes, related to type of disease, results in failure of correct expression (splicing of the mRNA) of the ClC-1 ion channel, due to accumulation of RNA in the cytosol of the cell.[9][10] The ClC-1 ion channel is responsible for the major part of chloride conductance in the skeletal muscle cell,[11] and lack of sufficient chloride conductance may result in myotonia, (see myotonia congenita). When the splicing of the mRNA was corrected in vitro, ClC-1 channel function was greatly improved and myotonia was abolished.[12]
Myotonia congenita
(Congenital myotonia) of which two types called Becker's disease and Thomsen's disease exist.[13] Both diseases are caused by mutations in the gene CLCN1 encoding the ClC-1 ion channel. More than 130 different mutations exist in total, and a large phenotypic variation is therefore present in this disease.[14] The mutations are loss-of-function mutations that render the ClC-1 ion channel dysfunctional to varying degrees, with reduced chloride conductance as a result. Reduced chloride conductance may result in myotonia, due to accumulation of potassium in the transverse-tubules in skeletal muscle (see myotonia congenita). This is the same genetic disease that makes certain strains of North American goats faint when scared.[citation needed]
Symptoms of myotonia (documented in myotonia congenita) are more frequently experienced in women during pregnancy.[15]
Myotonia could be caused by genetic mutations in the SCN4A gene that encodes the skeletal muscle sodium channel subtype 4 (Nav1.4). Some studies have suggested that changes in physiological pH could have modulatory effects on Nav1.4 sodium channels, which could have manifestations in myotonic phenotypes.[16]
Paramyotonia congenita
This disease results from mutation in the SCN4A gene encoding the
Potassium-aggravated myotonia
Hyperkalemic periodic paralysis
Also known as HyperKPP. Similar to Paramyotonia Congenita, where potassium exacerbates myotonia in many phenotypes, Hyperkalemic Periodic Paralysis is another disorder of the SCN4A gene where high blood potassium levels result in muscle weakness, muscle paralysis (through weakness or through over excitation preventing movement), and sometimes myotonia. Many phenotypes of HyperKPP result in issues regulating blood potassium levels, often cause it to be high or causing hyperkalemia, further exacerbating the condition.[citation needed]
Hypokalemic periodic paralysis
Also known as HypoKPP. Similar to HyperKPP above, except that it's triggered by (and often causes) low potassium levels and hypokalemia. It too can result in myotonia, in addition to weakness and paralysis (from both lack of and excess signal to muscles). It also has been found to occur due to gene mutations other than SCN4A.[citation needed]
Neuromyotonia
Neuromyotonia (also known as Isaac's Syndrome or NMT) causes peripheral nerve hyperexcitability that causes spontaneous muscular activity resulting from repetitive motor unit action potentials of peripheral origin. 100-200 cases have been reported.[21]
Other
Myotonia occurs also in certain types of limb-girdle muscular dystrophies, myofibrillary myopathies, distal myopathies, and inclusion body myopathies.[22] Other channelopathies may cause it as well.[3] It is also associated with Schwartz–Jampel syndrome.[23]
See also
References
- S2CID 20602810.)
{{cite journal}}
: CS1 maint: multiple names: authors list (link) CS1 maint: numeric names: authors list (link - ^ ISBN 978-0-323-05712-7, retrieved 28 May 2023
- ^ a b "Myotonia Information Page | National Institute of Neurological Disorders and Stroke". www.ninds.nih.gov. Retrieved 1 October 2019.
- PMID 24578711.
- S2CID 122401141.
- ^ "Isaacs Syndrome - Neurologic Disorders". Merck Manuals Professional Edition. Retrieved 28 May 2023.
- ISBN 978-3-642-92920-5, retrieved 28 May 2023
- S2CID 10804605.
- PMID 12150905.
- PMID 12150906.
- S2CID 17368122.
- PMID 18008009.
- PMID 19185184.
- S2CID 8336138.
- S2CID 22924091.
- PMID 29674667.
- S2CID 27141272.
- ^ Reference, Genetics Home. "Potassium-aggravated myotonia". Genetics Home Reference. Retrieved 17 November 2019.
- S2CID 12492661.
- S2CID 27141272.
- ^ RESERVED, INSERM US14-- ALL RIGHTS. "Orphanet: Search a disease". www.orpha.net. Retrieved 17 November 2019.
{{cite web}}
: CS1 maint: numeric names: authors list (link) - PMID 25313375.
- ^ "Schwartz Jampel syndrome | Genetic and Rare Diseases Information Center (GARD) – an NCATS Program". rarediseases.info.nih.gov. Retrieved 17 November 2019.