Myotonia is a symptom of a small handful of certain neuromuscular disorders characterized by delayed relaxation of the skeletal muscles after voluntary contraction or electrical stimulation. Myotonia is the defining symptom of many chanelopathies such as myotonia congenita, paramyotonia congenita and myotonic dystrophy. 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 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 life-threatening reactions to certain anaesthetics called anaesthesia-induced rhabdomyolysis.
Causes
Myotonia may present in the following diseases with different causes related to the ion channels in the skeletal muscle fiber membrane.
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 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,. When the splicing of the mRNA was corrected in vitro, ClC-1 channel function was greatly improved and myotonia was abolished.
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. This is the same genetic disease that makes certain strains of North American goats faint when scared. Symptoms of myotonia 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. 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 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. This inability of muscles to relax worsening with exercise is often termed "paradoxical myotonia." Paramyotonia also frequently triggered by exercise, cold, and potassium.
Potassium-aggravated myotonia results from in a mututation of the SCN4A gene that causes skeletal muscles to be unable to relax after contracting in bouts, typically following the consumption of potassium rich food. It is debated if potassium-aggravated myotonia is a distinct disease from Paramyotonia Congenita, and recent academic papers have classified it both ways.
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, 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.
Also known as HypoKPP. Similar to HyperKPP above, except that it's triggered by low potassium levels and hypokalemia. It too can result in myotonia, in addition to weakness and paralysis. It also has been found to occur due to gene mutations other than SCN4A.
Neuromyotonia 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.
