Myotonia congenita
Encyclopedia
Congenital myotonia is a genetic, neuromuscular channelopathy
that affects skeletal muscles (muscles used for movement). It is congenital, meaning that it is present from birth. Amongst other problems, it causes delayed relaxation of the muscles (myotonia
) and rigidity. The disorder is caused by mutations in the part of an ion channel gene responsible for shutting off electrical excitation in the muscles, causing muscle fiber membranes to have an unusually exaggerated response to stimulation (hyperexcitability). Symptoms include delayed relaxation of the muscles after voluntary contraction (myotonia), and may also include stiffness, hypertrophy (enlargement), sluggishness of the muscles, transient weakness in some mutations, pain, and cramping. The disorder is caused by a genetic mutation involving the chloride channel
of the muscles.
The prolonged muscle contractions, which occur most commonly in the leg muscles in recessive mutations, and more commonly in the hands, face, and eyelids in dominant mutations, are often enhanced by cold and inactivity, and in some forms is relieved by repetitive movement known as "the warm up effect". The warm up effect often diminishes quickly with rest.
The two major types of myotonia congenita are known as Thomsen disease
and Becker type myotonia congenita, the latter sometimes being called "generalized myotonia congenita". These diseases are distinguished by the severity of their symptoms and their patterns of inheritance. Becker disease usually appears later in childhood than Thomsen disease and causes more severe myotonia, muscle stiffness and pain. People with Becker disease often experience temporary attacks of muscle weakness, particularly in the arms and hands, brought on by movement after periods of rest. They may also develop mild, permanent muscle weakness over time. This muscle weakness is not seen in people with Thomsen disease. However, in recent times, as more and more of the individual mutations that cause myotonia congenita are identified, these limited disease classifications are becoming less widely used.
This disorder has high phenotype variability. Severity of symptoms can vary greatly between individuals and throughout the life of the individuals themselves. Part of this may be because there are over 80 different mutations that can cause the disorder, each with their own specifics, and also because myotonia congenita is an ion channel disorder, and ion channels are sensitive to internal and external environmental factors.
Adrenaline/epinephrine is well known to make myotonia worse in most individuals with the disorder, and a person with myotonia congenita may experience a sudden increase in difficulty with mobility in a particularly stressful situation during which adrenaline is released.
Due to the invisible nature of the disorder, the fact that those with myotonia congenita often appear very fit and able bodied, general lack of knowledge about the disorder by the general and medical community, and oftentimes by the individual themselves, and the potential for inconsistency with the symptoms, many people with myotonia congenita have experienced a degree of social persecution at one time or another because of the effects of their disorder.
Some form of myotonia congenita is estimated to affect 1 in 100,000 people worldwide.
Early symptoms in a child may include:
Possible complications may include:
. CLCN1 is the genetic code for the protein CLCN1
, that is critical for the normal function of skeletal muscle cells. This protein is used to make skeletal muscle chloride ion channels. In normal individuals, cessation of muscle contraction is initiated when the chloride channels open and shunt chloride ions into the muscle to halt the processes inducing the contraction. In people with myotonia congenita, the chloride channel is defective and the open gate probability potentials are shifted by a number of millivolts either in the positive or negative direction. In some mutations, the mutated proteins/channels are unstable and deteriorate quickly, or a defective endoplasmic reticulum exists, meaning the protein/channel cannot be transported efficiently to the cell surface. The result is prolonged muscle contractions, which are the hallmark of myotonia.
The two forms of myotonia congenita caused by CLCN1
mutations have different patterns of inheritance. Thomsen disease is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases of Thomsen Myotonia Congenita, an affected person has one parent with the condition. However some individuals may be so mildy affected that they do not notice the symptoms, while others may be very severely affected.
Becker disease is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder each carry one copy of the altered gene, but do not show signs and symptoms of the disorder.
With the advent of genetic testing, it has recently been found that some recessive mutations may occur in a dominant fashion in some individuals. The reason for this is not known.
Because several CLCN1 mutations can cause either Becker disease or Thomsen disease, doctors usually rely on characteristic signs and symptoms to distinguish the two forms of myotonia congenita. However, myotonia caused by CLCN1 mutations can occasionally be clinically indistinguishable from myotonia caused by sodium channel SCN4A
mutations.
SCN4A
mutations have been recognized as causing an atypical form of myotonia congenita not categorized as either Becker or Thomsen. Atypical myotonia congenita is also known as acetazolamide-responsive myotonia, a form of potassium-aggravated myotonia
.
A so-called Finnish heritage disease
, congenital myotonia is more common in Finland
and among ethnic Finns. A molecular study of the CLCN1 gene in 24 families in northern Finland, including 46 affected individuals, showed that although the inheritance appeared to be dominant (Thomsen type), in fact it is recessive (Becker type).
, phenytoin
, carbamazepine
, mexiletine
and other anticonvulsant drug
s. Physical therapy and other rehabilitative measures may also be used to help muscle function. Genetic counseling is available.
The disease is not fatal but when the muscles tighten up, the person with MC can fall. Depending what they fall on will determine the outcome of the injury. If a person with MC were to fall into water they may be unable to keep their head above water due to being unable to move hands & feet adequately.
Some Symptoms can include weakness in muscles on a sudden movement, life can be hard with Mytonia congenita but there are medications that can help.
Channelopathy
Channelopathies are diseases caused by disturbed function of ion channel subunits or the proteins that regulate them. These diseases may be either congenital or acquired .There are a large number of distinct dysfunctions known to be caused by ion channel...
that affects skeletal muscles (muscles used for movement). It is congenital, meaning that it is present from birth. Amongst other problems, it causes delayed relaxation of the muscles (myotonia
Myotonia
Myotonia is a symptom of a small handful of certain neuromuscular disorders characterized by the slow relaxation of the muscles after voluntary contraction or electrical stimulation. Generally, repeated effort is needed to relax the muscles, and the condition improves after the muscles have warmed...
) and rigidity. The disorder is caused by mutations in the part of an ion channel gene responsible for shutting off electrical excitation in the muscles, causing muscle fiber membranes to have an unusually exaggerated response to stimulation (hyperexcitability). Symptoms include delayed relaxation of the muscles after voluntary contraction (myotonia), and may also include stiffness, hypertrophy (enlargement), sluggishness of the muscles, transient weakness in some mutations, pain, and cramping. The disorder is caused by a genetic mutation involving the chloride channel
Chloride channel
Chloride channels are a superfamily of poorly understood ion channels consisting of approximately 13 members.Chloride channels display a variety of important physiological and cellular roles that include regulation of pH, volume homeostasis, organic solute transport, cell migration, cell...
of the muscles.
The prolonged muscle contractions, which occur most commonly in the leg muscles in recessive mutations, and more commonly in the hands, face, and eyelids in dominant mutations, are often enhanced by cold and inactivity, and in some forms is relieved by repetitive movement known as "the warm up effect". The warm up effect often diminishes quickly with rest.
The two major types of myotonia congenita are known as Thomsen disease
Thomsen disease
Thomsen disease, a form of Myotonia congenita, is a muscular genetic disorder characterized by muscle stiffness and an inability of the muscle to relax after a voluntary contraction...
and Becker type myotonia congenita, the latter sometimes being called "generalized myotonia congenita". These diseases are distinguished by the severity of their symptoms and their patterns of inheritance. Becker disease usually appears later in childhood than Thomsen disease and causes more severe myotonia, muscle stiffness and pain. People with Becker disease often experience temporary attacks of muscle weakness, particularly in the arms and hands, brought on by movement after periods of rest. They may also develop mild, permanent muscle weakness over time. This muscle weakness is not seen in people with Thomsen disease. However, in recent times, as more and more of the individual mutations that cause myotonia congenita are identified, these limited disease classifications are becoming less widely used.
This disorder has high phenotype variability. Severity of symptoms can vary greatly between individuals and throughout the life of the individuals themselves. Part of this may be because there are over 80 different mutations that can cause the disorder, each with their own specifics, and also because myotonia congenita is an ion channel disorder, and ion channels are sensitive to internal and external environmental factors.
Adrenaline/epinephrine is well known to make myotonia worse in most individuals with the disorder, and a person with myotonia congenita may experience a sudden increase in difficulty with mobility in a particularly stressful situation during which adrenaline is released.
Due to the invisible nature of the disorder, the fact that those with myotonia congenita often appear very fit and able bodied, general lack of knowledge about the disorder by the general and medical community, and oftentimes by the individual themselves, and the potential for inconsistency with the symptoms, many people with myotonia congenita have experienced a degree of social persecution at one time or another because of the effects of their disorder.
Some form of myotonia congenita is estimated to affect 1 in 100,000 people worldwide.
Early symptoms in a child may include:
- Difficulty swallowing
- Gagging
- Stiff movements that improve when they are repeated
Possible complications may include:
- Aspiration pneumonia (caused by swallowing difficulties)
- Frequent choking or gagging in infants (also caused by swallowing difficulties)
- Abdominal muscle weakness
- Chronic joint problems
Cause
Myotonia congenita is most commonly caused by mutations in the gene CLCN1CLCN1
Chloride channel protein, skeletal muscle is a protein that in humans is encoded by the CLCN1 gene. Mutations in this protein cause congenital myotonia....
. CLCN1 is the genetic code for the protein CLCN1
CLCN1
Chloride channel protein, skeletal muscle is a protein that in humans is encoded by the CLCN1 gene. Mutations in this protein cause congenital myotonia....
, that is critical for the normal function of skeletal muscle cells. This protein is used to make skeletal muscle chloride ion channels. In normal individuals, cessation of muscle contraction is initiated when the chloride channels open and shunt chloride ions into the muscle to halt the processes inducing the contraction. In people with myotonia congenita, the chloride channel is defective and the open gate probability potentials are shifted by a number of millivolts either in the positive or negative direction. In some mutations, the mutated proteins/channels are unstable and deteriorate quickly, or a defective endoplasmic reticulum exists, meaning the protein/channel cannot be transported efficiently to the cell surface. The result is prolonged muscle contractions, which are the hallmark of myotonia.
The two forms of myotonia congenita caused by CLCN1
CLCN1
Chloride channel protein, skeletal muscle is a protein that in humans is encoded by the CLCN1 gene. Mutations in this protein cause congenital myotonia....
mutations have different patterns of inheritance. Thomsen disease is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In most cases of Thomsen Myotonia Congenita, an affected person has one parent with the condition. However some individuals may be so mildy affected that they do not notice the symptoms, while others may be very severely affected.
Becker disease is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder each carry one copy of the altered gene, but do not show signs and symptoms of the disorder.
With the advent of genetic testing, it has recently been found that some recessive mutations may occur in a dominant fashion in some individuals. The reason for this is not known.
Because several CLCN1 mutations can cause either Becker disease or Thomsen disease, doctors usually rely on characteristic signs and symptoms to distinguish the two forms of myotonia congenita. However, myotonia caused by CLCN1 mutations can occasionally be clinically indistinguishable from myotonia caused by sodium channel SCN4A
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.
SCN4A
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 have been recognized as causing an atypical form of myotonia congenita not categorized as either Becker or Thomsen. Atypical myotonia congenita is also known as acetazolamide-responsive myotonia, a form of 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 that prevent muscles from relaxing normally...
.
A so-called Finnish heritage disease
Finnish heritage disease
A Finnish heritage disease is a genetic disease or disorder that is part of the Finnish disease heritage. Finnish heritage diseases are significantly more common in people whose ancestors were ethnic Finns, natives of Finland and Sweden. About 40 rare diseases are regarded as Finnish heritage...
, congenital myotonia is more common in Finland
Finland
Finland , officially the Republic of Finland, is a Nordic country situated in the Fennoscandian region of Northern Europe. It is bordered by Sweden in the west, Norway in the north and Russia in the east, while Estonia lies to its south across the Gulf of Finland.Around 5.4 million people reside...
and among ethnic Finns. A molecular study of the CLCN1 gene in 24 families in northern Finland, including 46 affected individuals, showed that although the inheritance appeared to be dominant (Thomsen type), in fact it is recessive (Becker type).
Treatment
Some cases of myotonia congenita do not require treatment, or it is determined that the risks of the medication outweigh the benefits. If necessary, however, symptoms of the disorder may be relieved with quinineQuinine
Quinine is a natural white crystalline alkaloid having antipyretic , antimalarial, analgesic , anti-inflammatory properties and a bitter taste. It is a stereoisomer of quinidine which, unlike quinine, is an anti-arrhythmic...
, phenytoin
Phenytoin
Phenytoin sodium is a commonly used antiepileptic. Phenytoin acts to suppress the abnormal brain activity seen in seizure by reducing electrical conductance among brain cells by stabilizing the inactive state of voltage-gated sodium channels...
, carbamazepine
Carbamazepine
Carbamazepine is an anticonvulsant and mood-stabilizing drug used primarily in the treatment of epilepsy and bipolar disorder, as well as trigeminal neuralgia...
, mexiletine
Mexiletine
Mexiletine belongs to the Class IB anti-arrhythmic group of medicines. It is used to treat arrhythmias within the heart, or seriously irregular heartbeats. It slows conduction in the heart and makes the heart tissue less sensitive. Dizziness, heartburn, nausea, nervousness, trembling, unsteadiness...
and other anticonvulsant drug
Anticonvulsant
The anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...
s. Physical therapy and other rehabilitative measures may also be used to help muscle function. Genetic counseling is available.
The disease is not fatal but when the muscles tighten up, the person with MC can fall. Depending what they fall on will determine the outcome of the injury. If a person with MC were to fall into water they may be unable to keep their head above water due to being unable to move hands & feet adequately.
Some Symptoms can include weakness in muscles on a sudden movement, life can be hard with Mytonia congenita but there are medications that can help.
External links
- YouTube Video of Fainting Goats with Myotonia Cogenita
- GeneReview/NCBI/NIH/UW entry on Myotonia Congenita
- YouTube Video of kittens with Myotonia Congenita - Its Not Just About the Goats
External links
- NINDS: Myotonia Congenita
- National Library of Medicine: Myotonia Congenita