5/01
Facts About Myopathies
Muscular Dystrophy Association
QUESTIONS AND ANSWERS
Part II
WHAT ARE THE SYMPTOMS AND TREATMENTS FOR EACH INHERITABLE MYOPATHY?
Myotonia congenita
Cause: This disease is caused by mutations in the gene for a chloride channel that's necessary for shutting off the electrical excitation that causes muscle contraction.
Inheritance: autosomal recessive (Becker-type), autosomal dominant (Thomsen's)
Onset: early to late childhood
Symptoms: The main problems faced by people with this disease are delayed muscle relaxation and muscle stiffness, typically provoked by sudden movements after rest. The stiffness can interfere with simple activities like walking, grasping and chewing, but is usually manageable by doing warm-up movements. The disease doesn't cause any muscle wasting; instead, it can sometimes cause muscle enlargement and increased muscle strength. Becker-type myotonia is the most common form of myotonia congenita, while Thomsen's disease is a very rare, relatively mild form.
Treatment: Someone who has myotonia congenita can lead a long, productive life, and can even excel at sports where strength is more important than agility. Your MDA clinic director can tell you about appropriate exercises, and if necessary, appropriate medications for dealing with muscle stiffness.
Paramyotonia congenita
Also called: Eulenberg's disease. (Some researchers regard paramyotonia congenita as a form of periodic paralysis.)
Cause: Sodium channels normally open to cause muscle excitation, and then close to end the excitation. In paramyotonia congenita, mutations in the muscle sodium channel gene prolong the channel's opening, causing higher-than-normal muscle excitation.
Inheritance: autosomal dominant
Onset: congenital
Symptoms: Paramyotonia congenita causes episodes of muscle stiffness and weakness — mostly in the face, neck, and upper extremities — that can last from minutes to hours. The stiffness is sensitive to exercise and cold. During brief exercise, overexcitation of muscles can cause stiffness, and with prolonged exercise, the overexcitation can occasionally lead to a fatigue-like weakness or even complete paralysis. Cold exposure can have similar effects, but some people experience muscle stiffness, weakness or, sometimes, temporary paralysis even when they're warm.
Treatment: By avoiding strenuous exercise and cold, most people with this condition can largely escape disability. But medications can be beneficial, especially for those who experience symptoms independent of exercise and cold. Your MDA clinic director can give you more information about these medications.
Periodic paralyses
In these diseases, faulty ion channels cause "attacks" of temporary muscle weakness that can result in temporary paralysis when severe.
There are different types of periodic paralysis, distinguished by what happens to potassium levels in the blood (specifically the fluid portion of the blood, or serum). In the hyperkalemic type (hyperKPP), high serum potassium levels can cause attacks. In the hypokalemic type (hypoKPP), low serum potassium levels can trigger attacks. (Kalemic refers to potassium; hyper means too much and hypo too little.)
Unlike the case for most myopathies, many people with hypoKPP and some people with hyperKPP experience progressive, permanent muscle damage that occurs independently of the attacks.
Hyperkalemic periodic paralysis
Cause: This disease is caused by distinct mutations in the muscle sodium channel gene. These mutations cause very slow closing of the sodium channel, leading to episodes of prolonged muscle excitation and weakness, and myotonia (muscle stiffness) in some people. It's not fully understood just how high levels of potassium interact with the defective sodium channels to trigger attacks.
Inheritance: autosomal dominant
Onset: childhood
Symptoms: Attacks of weakness usually last 15 minutes to an hour, but can last for a day or more. They can recur daily in severe cases. The attacks commonly occur after rest preceded by vigorous exercise, and can be aggravated by stress, pregnancy, or foods high in potassium. During attacks not caused by excess potassium intake, a person can become hyperkalemic or remain normokalemic (with no change in serum potassium levels). The frequency of attacks usually declines after middle age.
Treatment: To keep hyperKPP attacks to a minimum, stick to a diet rich in carbohydrates and low in potassium, and avoid strenuous exercise. When you do exercise, be sure to "cool down" with mild activity before resting.
During an attack, certain prescription drugs can be used to alleviate symptoms. Your MDA clinic director can give you more specific information on how to manage hyperKPP through appropriate exercise, diet and medication.
A father with hypokalemic periodic paralysis |
Hypokalemic periodic paralysis
Causes: This disease seems to be caused by a reduced availability of the sodium channels necessary for muscle excitation. That condition can be brought about by certain genetic defects in the sodium channels themselves, or strangely, by genetic defects in a channel that acts like a key to the muscle's calcium stores.
Inheritance: autosomal dominant
Onset: early childhood to adulthood
Symptoms: Attacks of weakness can occur daily and usually happen in the morning (during waking) or at night. Some people with the disease might experience only a few mild attacks in their lifetime. But the most severe attacks cause nearly full-blown paralysis.
Treatment: As in hyperKPP, attacks of hypoKPP can be prevented by avoiding strenuous activity and alleviated by medications. The dietary precautions, however, are nearly opposite. High-carbohydrate foods can trigger hypokalemia and contribute to an attack, while potassium intake can restore serum potassium levels and stem an oncoming attack. Ask your MDA clinic director for specific recommendations about diet, exercise and medications.
Central core disease
Causes: This rare disease appears to have multiple origins. But it's commonly caused by defects in a channel that acts like a gate to internal calcium stores. The defect causes leakage of calcium from the stores, which appears to damage muscle cells.
Inheritance: autosomal dominant, possibly autosomal recessive in rare cases
A boy with central core disease |
Onset: congenital
Symptoms: The disease is named for damaged areas within muscle cells (the cores), where the filament proteins are disorganized, and mitochondria (the tiny energy-producing factories that power muscle contraction) are missing. The impact of the cores on disease severity isn't clear.
This disease causes poor muscle tone (hypotonia) and persistent muscle weakness in infants. In rare cases, toddlers with the disease fail to walk at all, but usually they just reach motor milestones late. Older children and adults typically experience mild disabilities that worsen slowly with time, if at all. Due to chronic muscle weakness, many people develop skeletal deformities, including joint dislocations and scoliosis, or curvature of the spine that can compress vital internal organs.
People with this disease should be cautious about surgery because they face an especially high risk of malignant hyperthermia, a potentially fatal reaction to certain anesthetic drugs (see "Anesthesia").
Treatment: Someone with a severe form of central core disease might need a walker or other support devices for mobility, but many people require none. Unlike the case for other myopathies, people with this disease can benefit from exercise. Scoliosis and other skeletal problems can usually be corrected by use of orthopedic devices or by surgery. Your doctor or MDA clinic director can tell you more about the risks of surgery, and about anesthetic drugs that are safe.
Nemaline myopathy
Also called: rod body disease
Causes: This disease is caused by a variety of genetic defects, each one affecting one of the filament proteins required for muscle tone and contraction.
Inheritance: autosomal recessive, autosomal dominant
Onset: congenital to adulthood
Symptoms: The disease gets its name from the fact that the muscle cells contain abnormal clumps of threadlike material — probably disorganized filament proteins — called nemaline bodies (nema is Greek for "thread"). It causes weakness and poor tone (hypotonia) in the muscles of the face, neck and upper limbs, and often affects the respiratory muscles (those that control breathing).
A baby with nemaline myopathy |
The infantile-onset cases tend to be the most severe. Usually, infants with the disease lack the muscle strength and tone required for simple postures and movements. They also have serious difficulties with feeding and respiration. Although many infants with the disease die from respiratory failure or lung infections, some survive to adulthood. Affected children usually attain motor milestones slowly, and at puberty they might experience further weakening, necessitating use of a wheelchair.
For adults, even noncongenital forms of the disease can cause life-threatening respiratory problems. Adults also might experience swallowing and speech problems, and those with restricted mobility might develop scoliosis. However, even people who have had the disease since birth can lead active lives.
Treatment: An infant with nemaline myopathy usually requires a feeding tube to deliver nutrition and mechanical ventilation to support respiration. Children and adults also can benefit from respiratory support, since respiratory failure during sleep can be a persistent danger. Mobility and strength can be improved significantly by physical and orthopedic therapies. If you or your child has nemaline myopathy, your MDA clinic director can provide further information about treatments.
Myotubular myopathy
Also called: Centronuclear myopathy
Causes: The most common form (X-linked) is caused by defects or deficiencies of myotubularin, a protein thought to promote normal muscle development.
Inheritance: X-linked, autosomal recessive, autosomal dominant
A boy with myotubular myopathy |
Onset: congenital (X-linked); infancy to early adulthood (autosomal recessive); childhood to adulthood (autosomal dominant)
Symptoms: X-linked myotubular myopathy usually affects only boys, and causes severe muscle weakness and hypotonia noticeable at birth and sometimes before. The weakness and hypotonia interfere with posture and movement, and cause life-threatening difficulties with feeding and respiration. Sometimes, failure or infection of the lungs causes death in early infancy, but about two-thirds of boys survive to at least 1 year of age. Usually, these boys require a feeding tube and a mechanical ventilator. Most attain motor milestones slowly, and some might not walk at all. However, most boys gradually gain muscle strength, and a few grow up with little disability.
Independent of skeletal muscle problems, some boys with X-linked myotubular myopathy experience problems in other organ systems. These include anemia, gallstones, accelerated growth and serious liver abnormalities.
The autosomal forms affect boys and girls equally. They cause muscle problems similar in quality to those of the X-linked form, but the autosomal dominant form is considered mild and the recessive form intermediate. In these forms muscle problems grow worse with age. Problems with other organs haven't been reported.
Treatment: Until recently, nearly all infants with X-linked myotubular myopathy were expected to die within their first few months of life. But it's now clear that intensive, continuous support of feeding and ventilation can significantly improve their life expectancy and allow a high quality of life.
Respiratory support and monitoring also might be necessary for children and adults diagnosed with autosomal forms of myotubular myopathy. Also, most people with this disease benefit from physical and orthopedic therapies. Your MDA clinic director can give you more information about treatment.
HOW ARE THESE SIX INHERITABLE MYOPATHIES DIAGNOSED?
Usually, diagnosis begins with evaluation of the patient's personal and family history, and proceeds with physical and neurological examinations that test reflexes and strength. The exams can detect problems with muscle tone and contraction, and the histories can bring to light patterns of inheritance and conditions that might have aggravated the muscle problems in the past.
Given this information, a doctor can sometimes distinguish an inheritable myopathy from other diseases that affect muscle function, such as muscular dystrophies and neurological disorders. But to accurately identify the myopathy and plan an appropriate course of treatment, the doctor can use several specialized tests:
A muscle biopsy, the removal of a small piece of muscle tissue, is used to look for physical signs of muscle disease. Under the microscope, muscles affected by central core disease, nemaline myopathy or myotubular myopathy have fairly distinctive appearances.
Also, muscle biopsy can be used to see how isolated muscles respond to different potentially harmful conditions. For example, to determine a patient's susceptibility to malignant hyperthermia, a biopsied muscle can be tested for its reaction to potentially dangerous anesthetic drugs.
A muscle's activity can be measured by electromyography (EMG), which involves observing the electrical signals that a muscle produces during contraction. A needlelike electrode inserted into the muscle "reads" the electrical signals and sends them to a monitor called an oscilloscope. The technique usually causes some discomfort, but is useful for diagnosing channelopathies, which can show telltale abnormal signals on the oscilloscope.
Because the channelopathies sometimes just cause temporary muscle problems induced by changes in exercise, diet or temperature, the affected muscles might appear normal during a visit to the doctor's office. Therefre, the doctor might use a provocative test to elicit and evaluate a mild occurrence of the muscle problem.
An exercise test, which can involve anything from repeatedly making a fist to riding a stationary bicycle, usually can reveal symptoms of a channelopathy. Also, a doctor might test for periodic paralysis by having the patient consume safe doses of carbohydrate or potassium, or for paramyotonia congenita by immersing the patient's arm in cold water.
Doctors frequently administer a thyroid-stimulating hormone (THS) test to determine whether the myopathy is endocrine-related or to rule out the endocrine myopathies.
Finally, with just a blood sample, genetic tests can check for specific genetic defects that give rise to some of the inheritable myopathies.
These tests are safe, relatively painless and very accurate. However, because some of the genetic defects that cause inheritable myopathies remain to be discovered, a negative test result doesn't necessarily mean a person doesn't have a myopathy.
ENDOCRINE MYOPATHIES
Endocrine myopathies can occur when a gland produces too much or too little of a hormone. Hormones travel through the bloodstream and affect metabolism (a set of vital chemical reactions) in a variety of tissues, including muscle. Overproduction of the hormone thyroxine by the thyroid gland causes hyperthyroid myopathy, while underproduction causes hypothyroid myopathy.
A common cause of both myopathies is autoimmunity, a condition in which the immune system turns against part of the body — in this case, the thyroid. Sometimes, the endocrine myopathies occur with myasthenia gravis, another autoimmune disease that causes muscle weakness. Both myopathies can be almost completely alleviated by restoring normal thyroid activity, called the euthyroid state.
Hyperthyroid myopathy
Also called: thyrotoxic myopathy
Symptoms: This disease commonly involves weakness and wasting of muscles around the shoulders and sometimes the hips. There also can be weakness in muscles of the face and throat, and in the respiratory muscles. Severe cases can cause rhabdomyolysis (acute muscle breakdown).
Some people with hyperthyroid myopathy develop Grave's disease, damage to muscles that control movement of the eye and eyelids, which can lead to vision loss. Others develop thyrotoxic periodic paralysis, which involves temporary, but severe attacks of muscle weakness (see "Periodic Paralyses").
Treatment: Restoring normal thyroxine levels can be achieved with anti-thyroid drugs, but sometimes requires partial or complete surgical removal of the thyroid (thyroidectomy).
Hypothyroid myopathy
Symptoms: The most common symptoms include weakness around the hips and sometimes the shoulders, and a slowing of reflexes. Some people also experience muscle stiffness and painful muscle cramps. Severe cases can cause rhabdomyolysis.
Sometimes, the disease causes muscle enlargement along with muscle weakness. In adults, this condition is called Hoffman's syndrome, and in children, it's called Kocher-Debre-Semelaigne syndrome.
Treatment: Thyroxine levels can be brought up to normal with oral thyroxine pills. |
Back to Disease Booklets |
