Myotonia is a symptom of a small handful of certain

neuromuscular A neuromuscular junction (or myoneural junction) is a chemical synapse between a motor neuron and a muscle fiber. It allows the motor neuron to transmit a signal to the muscle fiber, causing muscle contraction. Muscles require innervation to ...

disorders characterized by delayed relaxation (prolonged contraction) of the

skeletal muscles Skeletal muscle (commonly referred to as muscle) is one of the three types of vertebrate muscle tissue, the others being cardiac muscle and smooth muscle. They are part of the somatic nervous system, voluntary muscular system and typically are a ...

after voluntary contraction or electrical stimulation, and the muscle shows an abnormal EMG. Myotonia is the defining symptom of many

channelopathies Channelopathies are a group of diseases caused by the dysfunction of ion channel subunits or their interacting proteins. These diseases can be inherited or acquired by other disorders, drugs, or toxins. Mutations in genes encoding ion channels, wh ...

(diseases of

ion channel Ion channels are pore-forming membrane proteins that allow ions to pass through the channel pore. Their functions include establishing a resting membrane potential, shaping action potentials and other electrical signals by Gating (electrophysiol ...

transport) such as

myotonia congenita ''Myotonia congenita'' is a congenital neuromuscular channelopathy that affects skeletal muscles (muscles used for movement). It is a genetic disorder. The hallmark of the disease is the failure of initiated contraction to terminate, often refe ...

paramyotonia congenita ''Paramyotonia congenita'' (PC) is a rare congenital autosomal dominant neuromuscular disorder characterized by "paradoxical" myotonia. This type of myotonia has been termed paradoxical because it becomes worse with exercise whereas classical my ...

and

myotonic dystrophy Myotonic dystrophy (DM) is a type of muscular dystrophy, a group of genetic disorders that cause progressive muscle loss and weakness. In DM, muscles are often myotonia, unable to relax after contraction. Other manifestations may include catarac ...

. Brody disease (a disease of

ion pump An ion pump (also referred to as a sputter ion pump) is a type of vacuum pump which operates by sputtering a metal getter. Under ideal conditions, ion pumps are capable of reaching pressures as low as 10−11 mbar. An ion pump first ionizes ...

transport) has symptoms similar to myotonia congenita, however, the delayed muscle relaxation is pseudo-myotonia as the EMG is normal. Other diseases that exhibit pseudo-myotonia are

myositis Myositis is a rarely-encountered medical condition characterized by inflammation affecting the muscles. The manifestations of this condition may include skin issues, muscle weakness, and the potential involvement of other organs. Additionally ...

glycogen storage diseases A glycogen storage disease (GSD, also glycogenosis and dextrinosis) is a metabolic disorder caused by a deficiency of an enzyme or transport protein affecting glycogen synthesis, glycogen breakdown, or glucose breakdown, typically in muscles an ...

hyperkalemic periodic paralysis Hyperkalemic periodic paralysis (HYPP, HyperKPP) is an inherited autosomal dominant disorder that affects sodium channels in muscle cells and the ability to regulate potassium levels in the blood. It is characterized by muscle hyperexcitability ...

, root disease, anterior horn cell disorders, Isaacs syndrome, and

Hoffmann syndrome Hoffmann syndrome is a rare form of hypothyroid myopathy and is not to be confused with Werdnig-Hoffmann disease (a type of spinal muscular atrophy). It was first documented in 1897 by Johann Hoffmann. It has adult-onset symptoms. It is compar ...

. 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 with disorders involving myotonia can have life-threatening reactions to certain

anaesthetics An anesthetic (American English) or anaesthetic (British English; see spelling differences) is a drug used to induce anesthesia ⁠— ⁠in other words, to result in a temporary loss of sensation or awareness. They may be divided into tw ...

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 (

sarcolemma The sarcolemma (''sarco'' (from ''sarx'') from Greek; flesh, and ''lemma'' from Greek; sheath), also called the myolemma, is the cell membrane surrounding a skeletal muscle fibre or a cardiomyocyte. It consists of a lipid bilayer and a thin ...

Myotonic dystrophy

Two documented types, DM1 and DM2 exist. In

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

). When the splicing of the mRNA was corrected in vitro, ClC-1 channel function was greatly improved and myotonia was abolished.

Myotonia congenita

(

Congenital myotonia ''Myotonia congenita'' is a congenital neuromuscular channelopathy that affects skeletal muscles (muscles used for movement). It is a genetic disorder. The hallmark of the disease is the failure of initiated contraction to terminate, often ref ...

) of which two types called Becker's disease and Thomsen's disease exist. Both diseases are caused by mutations in the gene

CLCN1 The CLCN family of voltage-dependent chloride channel genes comprises nine members (CLCN1-7, Ka and Kb) which demonstrate quite diverse functional characteristics while sharing significant sequence homology. The protein encoded by this gene regul ...

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

). This is the same genetic disease that makes certain strains of North American goats faint when scared. 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.

Paramyotonia congenita

This disease results from mutation in the gene encoding the

voltage-gated sodium channel Voltage-gated sodium channels (VGSCs), also known as voltage-dependent sodium channels (VDSCs), are a group of voltage-gated ion channels found in the membrane of excitable cells (''e.g.'', muscle, glial cells, neurons, etc.) with a permeability t ...

Na_v1.4 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 potential An action potential (also known as a nerve impulse or "spike" when in a neuron) is a series of quick changes in voltage across a cell membrane. An action potential occurs when the membrane potential of a specific Cell (biology), cell rapidly ri ...

s 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 Sodium channel protein type 4 subunit alpha is a protein that in humans is encoded by the ''SCN4A'' gene. The Nav1.4 voltage-gated sodium channel is encoded by the gene. Mutations in the gene are associated with hypokalemic periodic paralysis ...

). 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

Potassium-aggravated myotonia Potassium-aggravated myotonia is a rare genetic disorder that affects skeletal muscle. Beginning in childhood or adolescence, people with this condition experience bouts of sustained muscle tensing (myotonia) that prevent muscles from relaxing no ...

(PAM) results from in a mututation of the ''

'' 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.

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 Hyperkalemia is an elevated level of potassium (K+) in the blood. Normal potassium levels are between 3.5 and 5.0 mmol/L (3.5 and 5.0 mEq/L) with levels above 5.5mmol/L defined as hyperkalemia. Typically hyperkalemia does not cause symptoms. Oc ...

, further exacerbating the condition.

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 Hypokalemia is a low level of potassium (K+) in the blood serum. Mild low potassium does not typically cause symptoms. Symptoms may include feeling tired, leg cramps, weakness, and constipation. Low potassium also increases the risk of an a ...

. 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 in the calcium channel gene CACNA1S and, less frequently, in the

gene.

Neuromyotonia

Neuromyotonia Neuromyotonia (NMT) is a form of peripheral nerve hyperexcitability that causes spontaneous muscular activity resulting from repetitive motor unit action potentials of peripheral origin. NMT along with Morvan's syndrome are the most severe types ...

(also known as Isaac's Syndrome or NMT) causes peripheral nerve hyperexcitability that causes spontaneous

muscular MUSCULAR (DS-200B), located in the United Kingdom, is the name of a surveillance program jointly operated by Britain's Government Communications Headquarters (GCHQ) and the U.S. National Security Agency (NSA) that was revealed by documents release ...

activity resulting from repetitive motor unit action potentials of peripheral origin. 100-200 cases have been reported.

Other

Myotonia occurs also in certain types of limb-girdle muscular dystrophies, myofibrillary myopathies, distal myopathies, and inclusion body myopathies. Other

may cause it as well. It is also associated with

Schwartz–Jampel syndrome Schwartz–Jampel syndrome (SJS, also known as chondrodystrophic myotonia) is a rare genetic disease caused by a mutation in the perlecan gene (''HSPG2'') which causes osteochondrodysplasia associated with myotonia. Most people with Schwartz–Ja ...

References

External links

* {{Medical resources , DiseasesDB = 23079 , ICD10 = {{ICD10, G, 71, 1, g, 70 , ICD9 = {{ICD9, 359.2 , ICDO = , OMIM = , MedlinePlus = , eMedicineSubj = , eMedicineTopic = , MeshID = D009222 , SNOMED CT = 3434004 Symptoms and signs: Nervous system Myoneural junction and neuromuscular diseases Symptoms and signs: musculoskeletal system