NORD gratefully acknowledges Rabi Tawil, MD, Professor of Neurology, University of Rochester Medical Center, for assistance in the preparation of this report.
Paramyotonia congenita (PMC) is a rare non-progressive genetic disorder that affects the skeletal muscles. The disorder typically begins in infancy or early childhood. Affected individuals experience spells of muscle stiffness or when the muscles do not relax after contracting (myotonia). Symptoms can be triggered by exposure to the cold or after physical activity. The stiffness most commonly affects the muscles in the neck, face, arms and hands, however it can occur in the lower back and the muscles used for breathing. The stiffness of the muscles can get worse with repeated movements. There are also intermittent periods of a type of muscle weakness in which there is no muscle tone (flaccid paresis). This condition does not necessarily coincide with exposure to cold temperatures or myotonia. There is generally no wasting (atrophy) of muscles; however, there is often increase in bulk (hypertrophy) of muscles with this disorder. There is no cure to PMC; however, with the proper management of diet, lifestyle and medication, patients can lead normal lives. PMC is an autosomal dominant genetic condition caused by a mutation in the muscle sodium channel gene SCN4A.
PMC is classified as a form of periodic paralyses, a group of muscle disorders characterized by irregular episodes of muscle weakness or stiffness. PMC was first discussed in 1886 by von Eulenburg. It is considered the first recognized temperature-sensitive condition in humans.
Muscle stiffness in PMC is the inability for the muscles to relax in a timely manner after contracting (myotonia). The muscles most commonly affected are located in the face, neck and upper extremities, although it can affect the muscles used for breathing and swallowing, as well as muscles in the lower back. PMC is usually apparent during infancy and always presents by teenage years. Symptoms do not progress with age. Individuals with this disorder do not have wasting of muscles (atrophy) but often have an increase of muscle bulk (hypertrophy).
The severity of the muscle stiffness depends on the individual; some patients experience painful myotonia, while others experience painless myotonia. This condition becomes worse with exposure to cold and alleviated by warm temperatures. In addition, it can become more severe with exercise. Sudden overexertion can trigger muscle stiffness and overall weakness that can take several days to completely resolve. PMC can make small everyday activities difficult, such as letting go of small objects (e.g. pens or door knobs).
Some episodes of muscle stiffness can coincide with potassium intake; affected individuals are instructed to avoid certain food products rich in potassium.
Some patients with more severe PMC can experience shortness of breath or tightness in their chest muscles.
PMC is an autosomal dominant genetic condition caused by a change (mutation) in the SCN4A gene which codes for a sodium channel specific for skeletal muscles.
Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a mutated gene in the affected individual. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.
In some individuals, the disorder is due to a spontaneous (de novo) genetic mutation that occurs in the egg or sperm cell. In such situations, the disorder is not inherited from the parents.
Skeletal muscles move the body; muscle contractions pull on tendons, which are attached to the bones and causes the body to move. Muscle contractions are triggered by the flow of positively charged atoms (e.g. potassium and sodium) through channels into the skeletal muscles. These atoms carry electrical impulses necessary for normal function of the muscle cells. However, a mutation of the SCN4A gene alters the structure of the sodium channels. The sodium channels fail to regulate the flow of atoms into the muscles cells, and the ratio of sodium and potassium becomes unbalanced. The abnormal ratio interferes with normal muscle contraction and relaxation, causing bouts of muscle weakness and stiffness.
Most individuals with a SCN4A gene mutation have symptoms; however, there are a few who remain unaffected and are known as “carriers”.
PMC is a very rare disorder that affects males and females in equal numbers. The symptoms can begin during infancy, and are always apparent by the teenage years. It is estimated to affect fewer than 1 in 100,000 people.
When PMC is suspected, a test is administered to test the capacity of muscles to conduct electricity (electromyography). During the test, the muscles are chilled and electrical signals are recorded before and after the muscle is cooled. The electromyography (EMG) will show rapid repetitive electrical discharges. EMG cannot always diagnose PMC definitively, and further testing may be necessary.
Genetic testing on a blood sample will result in a definitive diagnosis by showing the presence of a characteristic mutation in the SCN4A gene.
The treatment of PMC is based on the individual’s symptoms; PMC can be handled on a day-to-day basis and many patients can lead normal lives. Individuals must be cautious to sudden exposures to very cold weather, as well as avoiding sudden heavy physical activity.
Muscle stiffness could also be triggered or enhanced by potassium-rich foods. Patients will need to learn how to manage their potassium-intake. They should avoid potassium-rich foods, avoid skipping meals and take carbohydrate rich snacks in between meals.
The aim of treatment is to reduce the intensity of acute symptoms and to prevent, as far as possible, further attacks. Some attacks are so mild that treatment is not necessary. However, in other instances drug therapy is required.
Treatment with medications that block the sodium channels such as mexiletine and lamotrigine may help reduce the stiffness related to myotonia. Some patients with PMC may benefit from acetazolamide or thiazide diuretic drugs to reduce the number of paralytic attacks.
Genetic counseling is recommended for patients and their families.
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