Myotonia (Myo from Greek; muscle, and Tonus from Latin; tension) is a symptom of a small handful of certain neuromuscular disorders characterized by delayed relaxation (prolonged contraction) of the skeletal muscles after voluntary contraction or electrical stimulation.
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 "Warm-Up" 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 suffering from disorders involving myotonia can have a life-threatening reaction to certain anaesthetics; one of these conditions occurs when the patient is under anaesthetic and is termed "Malignant hyperthermia".
Myotonia may present in the following diseases with different causes related to the ion channels in the skeletal muscle fibre membrane (Sarcolemma).
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. The ClC-1 ion channel is responsible for the major part of chloride conductance in the skeletal muscle cell, 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.
(Congenital Myotonia) of which two types called Becker's Disease and Thomsen's Disease exist. 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. 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).
Symptoms of myotonia (documented in myotonia congenita) are more frequently experienced in women during pregnancy.
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.
This disease results from mutation in the SCN4A gene encoding the voltage-gated sodium channel Nav1.4 in skeletal muscle fiber membrane. Mutations may alter the kinetics of the channel, such that the channel fails to inactivate properly, thus allowing spontaneous action potentials to occur after voluntary activity has terminated, prolonging relaxation of the muscle, or can result in paralysis if the relaxation is severely prolonged (see SCN4A).
- Gutmann, Laurie; Phillips, Lawrence H., 2nd (September 1991). "Myotonia congenita". Seminars in neurology. 11 (3): 244–8. doi:10.1055/s-2008-1041228. PMID 1947487.
- Birnberger, KL; Rüdel, R; Struppler, A (1 September 1975). "Clinical and electrophysiological observations in patients with myotonic muscle disease and the therapeutic effect of N-propyl-ajmaline". Journal of Neurology. 210 (2): 99–110. doi:10.1007/BF00316381. PMID 51920.
- Mankodi, A; Takahashi, MP; Jiang, H; Beck, CL; Bowers, WJ; Moxley, RT; Cannon, SC; Thornton, CA (July 2002). "Expanded CUG repeats trigger aberrant splicing of ClC-1 chloride channel pre-mRNA and hyperexcitability of skeletal muscle in myotonic dystrophy". Molecular Cell. 10 (1): 35–44. doi:10.1016/s1097-2765(02)00563-4. PMID 12150905.
- Charlet-B, N; Savkur, RS; Singh, G; Philips, AV; Grice, EA; Cooper, TA (July 2002). "Loss of the muscle-specific chloride channel in type 1 myotonic dystrophy due to misregulated alternative splicing". Molecular Cell. 10 (1): 45–53. doi:10.1016/s1097-2765(02)00572-5. PMID 12150906.
- Kwieciński, H; Lehmann-Horn, F; Rüdel, R (January 1984). "The resting membrane parameters of human intercostal muscle at low, normal, and high extracellular potassium". Muscle & Nerve. 7 (1): 60–5. doi:10.1002/mus.880070110. PMID 6700631.
- Wheeler, TM; Lueck, JD; Swanson, MS; Dirksen, RT; Thornton, CA (December 2007). "Correction of ClC-1 splicing eliminates chloride channelopathy and myotonia in mouse models of myotonic dystrophy". The Journal of Clinical Investigation. 117 (12): 3952–7. doi:10.1172/JCI33355. PMC 2075481. PMID 18008009.
- Lossin, Christoph; George AL jr (2008). "Myotonia Congenita". Advances in Genetics. 63: 25–55. doi:10.1016/S0065-2660(08)01002-X. PMID 19185184.
- Colding-Jørgensen, Eskild (July 2005). "Phenotypic variability in myotonia congenita". Muscle & Nerve. 32 (1): 19–34. doi:10.1002/mus.20295. PMID 15786415.
- Basu, A; Nishanth, P; Ifaturoti, O (July 2009). "Pregnancy in women with myotonia congenita". International Journal of Gynaecology and Obstetrics. 106 (1): 62–3. doi:10.1016/j.ijgo.2009.01.031. PMID 19368920.
- Ghovanloo MR, Abdelsayed M, Peters CH, Ruben PC (2018). "A Mixed Periodic Paralysis & Myotonia Mutant, P1158S, Imparts pH-Sensitivity in Skeletal Muscle Voltage-gated Sodium Channels". Scientific Reports. 8 (1): 13. doi:10.1038/s41598-018-24719-y. PMC 5908869. PMID 29674667.