Skeletal Muscle Disorders
Myopathies are diseases that affect muscles connected to bones (called skeletal muscles), such as the biceps in the upper arm and the quadriceps in the thigh. Myopathies can be caused by inherited genetic defects (e.g., muscular dystrophies), or by endocrine, inflammatory (e.g., polymyositis), and metabolic disorders.
Nearly all types of myopathy produce weakening and atrophy of skeletal muscles, especially those muscles closest to the center of the body (called the proximal muscles), such as the thigh and shoulder muscles. Muscles further from the center of the body (called the distal muscles), such as those in the hands and feet, are generally affected less often.
Some myopathies, such as the muscular dystrophies, usually develop at an early age, and others develop later in life. Some conditions worsen over time and do not respond well to treatment and others are treatable and othe remain stable. When few treatments are available that address the root cause of the disease, the myopathy is labeled "nonspecific muscle myopathy."
Worldwide incidence of inheritable myopathies is about 14%. Of all inheritable myopathyies, central core disease accounts for 16% of cases; nemaline rod myopathy accounts for 20%; centronuclear myopathy accounts for 14%; and multicore myopathy accounts for 10%.
Prevalence of muscular dystrophy is higher in males. In the United States, Duchenne MD and Becker MD occur in approximately 1 in 3300 boys. Overall incidence of muscular dystrophy is about 63 per 1 million.
Worldwide incidence of inflammatory myopathies (e.g., dermatomyositis, polymyositis) is about 5–10 per 100,000 people. These disorders are more common in women.
Incidence and prevalence of endocrine and metabolic myopathies are unknown. Corticosteroid myopathy is the most common type of endocrine myopathy and endocrine disorders are more common in women than in men. Metabolic myopathies are rare, but diagnosis of these conditions is increasing in the United States.
Types of Inhertiable Myopathy
The inheritable myopathies—muscular dystrophies, congenital myopathies, periodic paralysis—are caused by genetic defects that result in the absence or malformation of a protein essential for normal muscle function.
A genetic defect is an error in the sequence of genes in a person's DNA. The production of proteins that help form the human body is governed by codes in the DNA. For example, the segment of DNA that contains the coding sequence for dystrophin, a protein found in skeletal and heart muscle, is known as the gene for dystrophin.
Genes reside on chromosomes, which are made up of DNA. Humans normally have a total of 46 chromosomes, or 23 pairs: one set of chromosomes comes from the mother, one from the father. One of those 23 pairs of chromosomes is made up of the 2 chromosomes that determine a person's sex: a woman has 2 X chromosomes, and a man has 1 X chromosome and 1 Y chromosome. Autosomal genes are found on all but the X and Y chromosomes.
Inheritable genetic defects are either autosomal or X-linked (on the X chromosome), and dominant or recessive. If a gene is dominant, only one defective copy will cause disease. So a child who inherits one defective gene from either parent will have the disease. Most inherited myopathies are caused by an autosomal dominant genetic defect.
The muscular dystrophies, however, are caused by defective recessive X-linked genes. Both copies of a recessive X-linked gene must be defective in order for a girl to inherit the disease. This rarely occurs. Because boys have only one X-chromosome, a defective recessive x-linked gene will cause them to have the disease. This is why the muscular dystrophies and other diseases caused by recessive X-linked genetic defects affect only boys.
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Duchenne muscular dystrophy recessive gene on the X chromosome and occurs only in boys. On average, one in three cases results from a new genetic mutation in the mother or grandmother and has not been passed down from generation to generation for very long. Often, DMD is not diagnosed until a boy is about 4 or 5 years old, when he appears clumsy and falls frequently when he runs. Muscle weakening starts in the larger, proximal muscles of the legs. By about 12 years old, a boy with DMD often can no longer walk. Eventually, the muscles in the hands and feet (distal muscles) and the heart muscles weaken. A boy with DMD usually dies before the age of 20 from heart or respiratory problems. DMD is caused by an abnormality in the gene that codes for the muscle protein dystrophin. Dystrophin prevents the membrane that lines the muscle fiber (plasmalemma) from tearing when the muscle contracts. In DMD patients, very little dystrophin or dystrophin-like proteins exist. Without dystrophin, the membrane lining of the muscle is likely to tear, which leads to damage or death of the muscle fiber. In advanced DMD, all of the fibers in a muscle may be dead.
Becker muscular dystrophy (BMD) resembles DMD—the muscles are affected in much the same way, and it can cause heart complications—but it develops during adolescence or adulthood, not early childhood. BMD also is caused by a defective, recessive, X-linked gene that codes for dystrophin. Though, unlike DMD, there are dystrophin-like proteins in the muscles, but they are small and abnormal. Thus BMD is much less severe and has a slower progression than DMD.
Emery-Dreifuss muscular dystrophy
(EDMD) is a slowly progressing disease that affects children and young teenagers. Symptoms occur in the shoulder, upper arm, and shin muscles and can lead to heart complications. EDMD is caused by a defect of a recessive gene on the X chromosome.
Limb-girdle muscular dystrophy (LGMD) is a slowly progressing weakening of the shoulder and pelvis muscles that onsets anywhere from childhood to middle age. It eventually leads to cardiac and pulmonary complications. LGMD is caused by a defect of a recessive gene on either an autosomal or X chromosome.
Facioscapulohumeral muscular dystrophy (FHSD) is also known as Landouzy-Dejerine muscular dystrophy. It is a slowly progressing weakening of the facial, shoulder, and upper arm muscles and onsets anytime from childhood to early adulthood. Patients with FSH often experience bouts of speedy deterioration. FSHD is caused by a defect of an autosomal dominant gene.
Myotonic dystrophy is also known as Steinart's disease. It is a slowly progressing disease that onsets anytime from childhood through middle age. Unlike many myopathies, it affects both the proximal and distal muscles (i.e., feet, hands, face, neck). One of the characteristic symptoms is muscular contraction that fails to relax in the usual fashion (myotonia). It is caused by a defect of an autosomal dominant gene. People with MD may have difficulties swallowing and may suffer from sleeping disorders. Some people with MD are also mentally disabled. Most patients suffer from abnormal heart rhythms.
Oculopharyngeal muscular dystrophy (OPMD) is a slowly progressing disease that first affects the eyelid and throat muscles and causes swallowing difficulties. It affects adults through middle age. OPMD is caused by a defect of an autosomal dominant gene.
Distal muscular dystrophy is a slow progressive weakening of the hands, forearms, and lower legs. It affects adults 40 to 60 years old and, unlike other muscular dystrophies, is not progressive.
The congenital myopathies are autosomal dominant inheritable diseases that are evident at or soon after birth.
Congenital muscular dystrophy
(CMD) is evident at birth and causes general muscle weakness and joint deformities. It progresses very slowly and in its severe form (Fukuyama) affects mental function. CMD is caused by a defect of an autosomal dominant gene.
Central core disease is a slowly progressing skeletal muscle disorder that, unlike most of the muscular dystrophies, is not life-threatening. It is called central core disease because the muscle cells associated with the disease have an abnormal light inner core surrounded by a dark circle. Central core disease develops before early infancy and its symptoms include hip displacement, an inability to jump and run smoothly, and general weakening of the muscles.
Myotonia congenital, also known as Thomsen's disease, is a nonprogressive muscle disorder that develops from infancy to childhood. Myotonia is characterized by stiff muscles that take a long time to relax after contraction. It is generally not painful. Unlike many other myopathies, the muscles that are affected (arms, legs, and face) enlarge and do not weaken.
Paramyotonia congenital, also known as Eulenberg's disease, is evident at birth, and like myotonia congenita, is characterized by stiff muscles that take a long time to relax after contraction, it is not progressive, and it does not cause muscle weakening. It is triggered by cold temperatures. The hands become clumsy, the face rigid, and the muscles in the forearm stiff.
also known as centronuclear myopathy, is a slowly progressive disease that causes drooping of the eyelids, foot drop, facial weakness, and other muscle weakness. It is evident at birth to infancy and is rarely fatal. The weakened muscles usually have no reflexes.
Nemaline myopathy, also known as Rod body disease, develops from birth to adulthood and is nonprogressive and usually not fatal. Symptoms include weakening of the leg, arm, and trunk muscles and some weakening of various facial and throat muscles. The affected muscles usually have poor reflexes. There is a particularly severe type of nemaline myopathy that, if present at birth, causes death due to breathing complications.
Metabolic myopathies are characterized by the absence of a substance that is essential for normal muscle function and are associated with genetic defects. In many of these disorders, the symptoms increase after exercise, and a person may experience severe muscle pain during exercise. This is usually due to a lack of oxygen and the absence of the chemicals necessary for maintaining the energy level of the muscle. There are numerous metabolic myopathies.
McArdle's disease results from a genetic defect that causes phosphorylase deficiency. It usually develops in adolescence and is characterized by cramps after exercise, and sometimes muscle weakening. Most people can avoid progression of the disease by avoiding strenuous exercise, although about one-third of all people with McArdle's disease eventually have permanent muscle weakness.
Phosphofructokinase deficiency, also known as Tarui's disease, is also caused by a genetic defect. Symptoms include cramping after exercise and sometimes muscle weakness.
Carnitine palmityltransferase deficiency causes muscle tissue breakdown and pain. An inherited autosomal recessive genetic mutation is implicated. This condition appears to be more common in men than women.
Periodic paralysis is associated with an abnormal level of potassium in the blood. There are three types of periodic paralysis: hypokalemic (low levels of potassium in the blood), hyperkalemic (high blood potassium level), and normokalemic (normal blood potassium level). All involve periodic attacks of muscle weakening and none are lethal. The muscles function normally between attacks. Hyperkalemic and normokalemic paralysis develop from infancy through childhood.
Several genetic defects have been linked to hyperkalemic periodic paralysis, some of which are also linked to myotonia and paramyotonia congenita. Paralysis attacks occur variably, from every few days to every few years. The number and severity of attacks tend to decrease with age.
Hypokalemic paralysis usually appears in adolescence through young adulthood and seems to be triggered by strenuous exercise, eating too many carbohydrates, and various medications. It usually lasts from a few hours to a week and begins in the back, shoulder, and thigh and spreads to the arms, neck, and lower legs. Administering potassium during an attack can alleviate symptoms, although there is no long-term treatment.
Hyperkalemic paralysis is also triggered by strenuous exercise, as well as cold temperatures. Often it is coupled with myotonia. Usually the legs and arms are mostly affected.
paralysis is also triggered by exercise as well as various drugs. It is similar to hyperkalemic paralysis, but there is no altered level of potassium in the blood during an attack. This type is caused by a defect of an autosomal dominant gene.
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OTHER TYPES OF MYOPATHIES
Endocrine myopathies are caused by underlying conditions caused by the over- or underproduction of hormones. These conditions can develop in children and adults and usually respond well to treatment.
Steroid myopathy is the most common endocrine muscle disease. Steroid excess, whether caused by an adrenal gland disorder (e.g., Addison disease) or chronic administration of glucocorticoid drugs, causes muscle weakness and wasting.
Hyperthyroid myopathy is caused by the thyroid gland producing too much thyroxine. Its symptoms include weakening and wasting of the muscles, especially in the shoulders and hips, and sometimes the eyes.
Hypothyroid myopathy is caused by the underproduction of thyroxine and results in muscle weakening in the legs and arms. The muscles may become enlarged.
Cushing's disease, characterized by overproduction of hormones produced by the pituitary and adrenal glands, cause myopathy.Excess parathyroid hormone results in hypercalcemia, which causes proximal muscle pain and weakness. Hormone-secreting tumors (e.g., growth-hormone secreting pituitary adenoma) can cause endocrine disorders that produce myopathy.
Inflammatory myopathies are autoimmune disorders. An autoimmune disorder is caused by the body's immune system mistakenly attacking healthy tissue. In this case, it attacks healthy muscle fibers and causes inflammation, which in turn damages the muscle. It is not known what triggers this autoimmune response.
The severity and progression of these myopathies vary considerably. Some people develop other disorders, such as abnormal heart rhythms, lung disease, gastrointestinal problems, arthritis, or cancer.
Polymyositis (PM) can occur at any age in either sex, but is more common in children and in women between 40 and 60 years old. Most people with PM suffer muscle aches, cramping, and tenderness. The muscle weakness is, however, quite intense and may fluctuate over weeks to months. It is often worse in the neck, arms, and thighs, making it difficult to stand up from a sitting position. Many patients also experience fever, general discomfort (malaise), and loss of appetite.
Dermatomyositis (DM) is characterized by a skin rash and all of the muscle symptoms of PM. The rash is a purple discoloration around the eyes and on the cheeks but may also appear on other parts of the body. Eventually the skin becomes thin and fragile. DM most commonly develops in children between the ages of 5 and 14 years. People who have DM have an increased risk for developing cancer.
Exposure to certain medications, chemicals, and excessive alcohol intake can damage skeletal muscle. Drugs and types of chemicals that can cause myopathy include the following:1 Anesthetics (e.g., lidocaine, mepivacaine, ethyl chloride)
2 Cholesterol-lowering Agents (e.g., clofibrate,
lovastatin, simivastatin, niacin)
3 Glucocorticoids (e.g., triamcinolone, dexamethasone,
4 Narcotics (e.g., cocaine, heroin, meperidine)
5 Other Drugs (e.g., zidovudine, D-penicillamine,
procainamide, chloroquine, gallamine)
6 Herbicides, Insecticides, Flame Retardants
CAUSES AND RISK
myopathies are caused by a genetic defect. The most common muscular
dystrophies, Duchenne MD and Becker MD, result from a genetic defect on the X
Risk factors for
other types of myopathy include the
Autoimmune disorders (e.g., myasthenia gravis, scleroderma, thyroiditis)
Endocrine disorders (e.g., Cushing syndrome,
hypothyroidism, hyperthyroidism, Addison disease)
Exposure to toxins (e.g., herbicides,
insecticides, flame retardant chemicals)
Infection (e.g., HIV, Lyme disease, trichinosis)
Vitamin D deficiency, vitamin E or A toxicity
Medication (e.g., some antihistamines, long-term
Metabolic disorder (e.g., glycogen and lipid
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MYOPATHY SIGNS AND
Other typical symptoms of muscle disease include the
Although symptoms depend on the type of myopathy,
some generalizations can be made. Skeletal muscle weakness is the
hallmark of most myopathies, with some noticeable exceptions, such as myotonia
and paramyotonia congenita. In these two inheritable muscular disorders, the
muscles become enlarged, rather than weakened and atrophied, and do not relax
In most myopathies, weakness occurs primarily in the
muscles of the shoulders, upper arms, thighs, and pelvis (proximal muscles). In
some cases, the distal muscles of the hands and feet may be involved during the
advanced stage of disease.
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