Myotonia congenita

Myotonia congenita
Specialty	Neurology

Congenital myotonia (also myotonia congenita) 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 later 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 CLCN1. 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).

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 quinine, phenytoin, carbamazepin and mexiletine and other anticonvulsant drugs. 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.

See also

• Fainting goat

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