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Facts about myopathies.


Before MDA's founding in 1950, very little was known about neuromuscular diseases. In fact, only one physician in the United States was devoting his practice to caring for people with these diseases. Because of the Association's efforts, that picture has changed drastically. Much has been learned about the nature and causes of many neuromuscular diseases, and this information is the foundation upon which current MDA research and treatments rest. Indeed, a number of the neuromuscular diseases discussed in this pamphlet were first described by MDA-supported scientists, and much of the present knowledge about these disorders is a result of continuing MDA research. The 10 neuromuscular diseases detailed here are classified as either inheritable myopathies or myopathies due to endocrine abnormalities. The term inheritable myopathies refers to disorders caused by defective genes, while the term myopathies due to endocrine abnormalities refers to conditions caused by faulty glands that control hormone levels. These myopathies occur rarely and are not often fatal. The effects are generally mild, primarily leading to muscle weakness and affecting movement. Only rarely do patients become wheelchair-dependent. Many of these myopathies involve occasional attacks that produce a temporary muscle weakness or stiffness, and patients can learn what circumstances trigger the attacks. Treatments have been developed for some of these conditions, and knowledge is expanding rapidly about others. Through an unparalleled variety of programs and services, MDA is committed to helping people with these myopathies and their families. These programs include research projects aimed at finding causes and cures, as well as medical services provided at local MDA clinics. MDA-funded scientists have already made encouraging progress toward uncovering genes that, when defective, may cause several of the myopathies. The discovery of those genes promises to lead to a more complete understanding of these particular disorders, pointing the way to effective treatments. What are the 10 major types of myopathies?

There are eight inheritable myopathies: central core disease, myotonia congenita, paramyotonia congenita, myotubular myopathy, nemaline myopathy, hypokalemic periodic paralysis, hyperkalemic periodic paralysis and normokalemic periodic paralysis. The two myopathies caused by endocrine abnormalities are hyperthyroid myopathy and hypothyroid myopathy.


What causes the inheritable myopathies?

Each of the eight inheritable myopathies is caused by a defect in a gene. Genes are the body's basic units of heredity and determine inherited characteristics such as eye and hair color as well as less obvious traits such as neuromuscular functions. Humans are estimated to have between 50,000 and 100,000 genes, and each may have more than one function.

How do gene defects cause these diseases?

Among the functions genes are responsible for is directing the production of proteins that are necessary for establishing and maintaining healthy cells. During its lifetime, a muscle cell produces thousands of proteins. With each of the inheritable diseases of muscle, a gene defect leads to an absence of or abnormality in one of the proteins necessary for normal functioning of a muscle cell.

The inheritable myopathies are presented here in five groups.


Age of Onset: Birth to early infancy

What is central core disease?

First described in 1956, central core disease is a slowly progressive disease of voluntary muscle, or those necessary for movement. It is disabling but not life-threatening. it normally affects the hips and legs, although it can eventually involve most of the body's voluntary muscles.

People who have central core disease are sometimes susceptible to malignant hyperthermia, a condition brought on by anesthesia during surgery. Malignant hyperthermia causes a rapid, and occasionally fatal, rise in body temperature and produces muscle stiffness.

Investigators now know which region of which chromosome holds the flawed gene responsible for central core disease and malignant hyperthermia. Different defects in the same gene on chromosome 19 may lead to the two disorders.

Why is it called central core disease?

Central core disease's name comes from the appearance of affected muscle cells taken from people with the disorder. When stained for examination, these cells look as though they have a light-colored inner core within a dark circle, while the entire cell is dark in normal cells. The significance of this "central core" is still not clear.

What are the symptoms of central core disease?

Symptoms of central core disease often are not very severe. A mild general weakness and hip displacement are characteristic of the disease. Individuals having the disorder reach motor skill milestones slowly. Affected children find that they cannot run smoothly and that jumping is often impossible.


What are myotonia congenita and paramyotonia congenita?

Myotonia congenita and paramyotonia congenita were first described in the 19th century and are nonlethal and generally nonprogressive diseases of voluntary muscle. The principal feature of these disorders is myotonia, a condition in which muscles are slow to relax after contracting and are consequently difficult to move. This myotonia may be severe enough to interfere with normal activity.

Different defects in the same gene on chromosome 17 appear to cause paramyotonia congenita and at least one form of myotonia congenita, as well as hyperkalemic periodic paralysis. Two other forms of myotonia congenita appear to be caused by a defective gene on chromosome 7.

What is the difference between myotonia congenita and paramyotonia congenita?

Myotonia congenita and paramyotonia congenita differ from each other in the age of onset, muscles affected and the form of myotonia present.

Myotonia Congenita

Alternate Names: Thomsen's disease Age of Onset: Infancy to childhood

Myotonia congenita affects the arms, the legs and the face, including the eyelids. Muscle wasting is not characteristic of the disease. Instead, pronounced muscle enlargement, particularly of the thighs, shoulders and forearms, may be present.

Cold, fatigue, emotional stress or long periods of rest, such as a night's sleep, can bring on myotonia, or stiffness. The myotonia is generally not painful and can often be "worked off" with repeated movement. One form of myotonia congenita does not become more severe with time, while another form does, progressing until the early adult years, by which time the disorder may have led to some muscle weakness.

Paramyotonia Congenita

Alternate Name: Eulenberg's disease Age of Onset: Birth

Paramyotonia congenita causes a type of myotonia in which exposure to cold brings on prolonged muscle contraction in the face, forearms and hands. It gives the face a stiff expression and makes the hands clumsy. The condition is seldom progressive and, like most forms of myotonia congenita, is not associated with muscle wasting.

However, it differs from myotonia congenita in being more readily triggered by cold and in that the myotonia in paramyotonia congenita becomes worse rather than better with repetitive activity. Also, the contractions in paramyotonia congenita last longer and weakness may continue for up to half an hour.


Alternate Name: Centronuclear myopathy Age of Onset: Birth to infancy

What is myotubular myopathy?

First described in 1966, myotubular myopathy is a slowly progressive, but rarely fatal, disease of voluntary muscle.

Why is it called myotubular myopathy?

The name myotubular myopathy comes from the appearance of affected muscle fibers that resemble myotubes, a type of fiber normally found only during fetal development. The disease is also called centronuclear myopathy because the nuclei of affected muscle cells are found in the center of each cell instead of at the periphery as is true with healthy muscle cells.

What are the symptoms of myotubular myopathy?

Common symptoms of myotubular myopathy are drooping of the upper eyelids, facial weakness and foot drop, as well as some weakness of the limbs and trunk. People with the disease almost always lack reflexes in the affected muscles.


Alternate Name: Rod body disease Age of Onset: Birth to adulthood

What is nemaline myopathy?

First described in 1963, nemaline myopathy is a disease of voluntary muscle that is often nonprogressive. The most common form of the disease is not fatal, although a rare form of the disorder is.

What is it called nemaline myopathy?

Nemaline means threadlike, and researchers chose this name because of the presence in affected muscle cells of threadlike or rod-shaped material. The significance of these rodlike bodies is still not clear.

What are the symptoms of nemaline myopathy?

People with nemaline myopathy have moderate weakness in their leg, arm and trunk muscles, accompanied by some mild weakness of the face, tongue and throat muscles. Reflexes are decreased or absent. Affected children often have long, narrow faces with high-arched palates and slender body musculatures. High-arched feet and curvature of the spine are common, and the jaw may also be malformed.

The severest form of nemaline myopathy usually appears at birth. Affected children have a marked weakness and a lack of muscle tone. Their respiratory muscles are weak, and death often occurs in the first few years of life due to respiratory failure.


What is periodic paralysis?

First described in the 19th century, periodic paralysis is a general term applied to three distinct, though possibly related, nonlethal disorders of voluntary muscle. The three types of periodic paralysis are hypokalemic, hyperkalemic and normokalemic. All three are characterized by interrmittent attacks of weakness, during which affected muscles become slack, weak and unable to contract. However, between attacks, the affected muscles usually work normally.

The names of the three forms of the disease are derived from the measure of potassium (kalemic) levels in the blood during an attack. Potassium may fall, rise or remain constant during an attack.

Defects in a gene on chromosome 17 appear to give rise to hyperkalemic periodic paralysis. A number of different defects in this same gene have been found to be associated with hyperkalemic periodic paralysis, at least one form of myotonia congenita and paramyotonia congenita.

How frequent are attacks of periodic paralysis?

Intervals between attacks vary from days to months and even years.

Does periodic paralysis become worse with age?

Periodic paralysis can cause progressive weakness, but the number of attacks and their severity tend to decrease with age and the attacks may disappear altogether, especially in women.

How do the three types of periodic paralysis differ from one another?

Hypokalemic, hyperkalemic and normokalemic periodic paralysis differ from one another in age of onset, precipitating factors, clinical characteristics and response to therapy.

Hypokalemic Periodic Paralysis

Age of Onset: Adolescence to young


Hypokalemic periodic paralysis, characterized by a fall in potassium levels in the blood, was the first of the three types of periodic paralysis to be identified and studied. It is probably the most common form of periodic paralysis. The administration of potassium during an attack may relieve symptoms. However, long-term usage of potassium to prevent attacks often has no effect.

Attacks of hypokalemic periodic paralysis are usually triggered by exercising too strenuously, eating too many carbohydrates or taking drugs such as insulin. These attacks can last two to three hours or as long as a week, and they often begin at night. Initially they affect the back, shoulder and thigh muscles and then spread to the arms, neck and lower legs. Speech and breathing are also affected, although generally not drastically.

Hyperkalemic Periodic Paralysis

Alternate Name: Adynamia episodica

hereditaria Age of Onset: Infancy to early childhood

Individuals with hyperkalemic periodic paralysis, not described until 1956, display a rise in potassium levels in the blood during episodes. They often experience myotonia, the inability to immediately relax a contracted muscle. However, this myotonia is neither muscle-wasting nor progressive, as it is in myotonic dystrophy, nor does it affect all muscle groups as does myotonia congenita.

Attacks are usually triggered by strenuous exercise, administration of potassium or by exposure to cold. Such attacks may induce myotonia, paralysis or a mixture of both. They frequently begin with pain, numbness and a tingling sensation in the legs. While the consequent weakness may be felt in all parts of the body, the muscles of the arms and the legs are primarily involved. Attacks are typically more frequent but shorter in duration than those of hypokalemic periodic paralysis.

Normokalemic Periodic Paralysis

Age of Onset: Infancy to childhood

Blood potassium does not rise above or fall below normal levels during an attack of normokalemic periodic paralysis. However, attacks are more severe and generally last longer than those of either hypokalemic or hyperkalemic periodic paralysis. Exercise or a number of different drugs may trigger these attacks. Normokalemic periodic paralysis is often similar to hyperkalemic periodic paralysis.

How are the muscle diseases known as inheritable myopathies inherited?

Most of these myopathies are inherited in an autosomal dominant pattern, which means that a child need only inherit the defective gene from one parent in order to have the disease. The parent transmitting the gene also has the disorder, and each of his or her children has a 50 percent chance of inheriting the disease.

Autosomal refers to the fact that the genetic defect may be located on any of the 46 rodlike structures, called chromosomes, that hold the genes found in each human cell, except the two that determine a person's sex. With an autosomal inheritance pattern, male and female children are equally affected.

In rare instances, some forms of these diseases appear to follow an autosomal recessive pattern or an X-linked recessive pattern. A disease governed by the recessive pattern requires that both parents, who usually do not have the disease, pass on the defective gene in order for a child to be affected by the disease. Each child of such parents has a 25 percent chance of inheriting and showing signs of the disease. A 50 percent chance exists that such a child will inherit the defective gene from only one parent and, therefore, will be a carrier of the flawed gene and will usually not show signs of the disease.

X-linked refers to a gene that is on the X chromosome, which along with the Y chromosome determines sex. Male children have one X chromosome and one Y chromosome, while females have two X chromosomes. Therefore, inheritance of a gene on the X chromosome is different from that for one on an autosomal chromosome.

In the X-linked recessive pattern, the disease develops mostly in males. Females who inherit the defective gene are usually carriers like their mothers and can pass the disease on to their sons but rarely show signs of the disease themselves.

Central core disease, some forms of myotonia congenita, myotubular myopathy (possibly), some forms of nemaline myopathy, paramyotonia congenita and periodic paralysis follow the autosomal dominant pattern. One form of myotonia congenita and some forms of nemaline myopathy follow the autosomal recessive pattern. Some forms of myotubular myopathy follow the X-linked recessive pattern.


What are myopathies due to endocrine abnormalities?

Myopathies due to endocrine abnormalities are neuromuscular diseases caused by a malfunctioning gland. This defective gland, which may be one of several in the body, produces either too much or too little of substances called hormones, which are carried in the bloodstream to parts of the body such as muscles to regulate their functions. Problems in hormone production may cause muscle weakness.

Which myopathies due to endocrine abnormalities does MDA cover?

MDA provides services to individuals who have hyperthyroid myopathy and hypothyroid myopathy. Both are nonlethal disorders produced by a faulty thyroid gland.

What are the differences between hyperthyroid myopathy and hypothyroid myopathy?

Hyperthyroid myopathy and hypothyroid myopathy differ in the muscles affected and the presence or absence of muscle wasting.

Hyperthyroid Myopathy

Age of Onset: Childhood to adulthood

An excess of thyroxine produced by the thyroid gland causes hyperthyroid myopathy. Weakness, accompanied by some muscle wasting, of the shoulders and the hips is common. The disease may also affect the muscles controlling eye movement. Its severity depends upon the success in treating the underlying thyroid condition.

Hypothyroid Myopathy

Age of Onset: Childhood to adulthood

Insufficient hormone production by the thyroid gland causes hypothyroid myopathy. The disease produces weakness of arm and leg muscles, as well as stiffness and cramps. In children with this disease, muscle enlargement may occur. The disorder's severity depends upon the success in treating the underlying thyroid condition.


How are the inheritable and endocrine myopathies diagnosed?

When a person sees a doctor because of muscle weakness or other symptoms of neuromuscular disease, an experienced physician makes a diagnosis by carefully evaluating a person's medical history and by a thorough physical examination. Diagnostic tests are used to help the physician distinguish between the different forms of myopathy, as well as between myopathies and other neuromuscular disorders. if an inheritable myopathy is suspected, family history is also investigated.

What are some common diagnostic tests?

A major diagnostic test for periodic paralysis is the measurement of potassium levels in blood samples taken from individuals suspected of having the disease. The administration of potassium can also differentiate between the hypokalemic and hyperkalemic forms of the disease.

Studying a small piece of muscle taken from an individual during a muscle biopsy is a useful part of the diagnosis for a number of myopathies, especially central core disease, nemaline myopathy and myotubular myopathy. The biopsy often allows a physician to determine which myopathy a person has.

Another diagnostic test is the electro-myogram (EMG), which is particularly helpful in the diagnosis of myotonia congenita or paramyotonia congenita. Placing small electrodes into muscle to measure electrical activity provides information indicating the health of the body's muscles and nerves.

Are the inheritable and endocrine myopathies contagious?

No. These inheritable and endocrine neuromuscular diseases are not contagious.

Are there any cures or treatments the inheritable and endocrine myopathies?

Attacks of hypokalemic and hyperkalemic periodic paralysis can often be treated by medication and changes in diet, but no treatment exists for central core disease, nemaline myopathy and myotubular myopathy.

When myotonia congenita is severe enough to require treatment, it can be temporarily relieved by one of a number of drugs. However, these do not affect the underlying disease process, and attacks may still occur. With paramyotonia congenita, specific treatment of the symptoms is often unnecessary.

Treating the underlying thyroid abnormality is often effective in correcting the muscle problems connected with either hyperthyroid myopathy or hypothyroid myopathy.

RELATED ARTICLE: MDA's Search for a Cause

MDA-funded scientists are pursuing a number of promising leads in their quest to understand the causes of the myopathies described in this brochure. A major focus of their research is the search for genes that, when defective, cause the inheritable disorders. Once these genes are isolated, researches can begin to uncover how gene defects lead to each of the diseases and develop treatments for them. Thus far, locations of the defective genes responsible for central core disease, hyperkalemic periodic paralysis, paramyotonia congenita and at least three forms of myotonia congenita are known. Other MDA-backed scientists are studying how various essential substances such as sodium move in and out of the muscle cell. These chemicals play an important role in normal muscle contraction, and any defects in the mechanisms controlling their movement could lead to various neuromuscular disorders such as myotonia congenita, paramyotonia congenita and periodic paralysis. Some MDA-sponsored researchers are conducting studies in order to learn the exact functions of the healthy versions of the proteins whose abnormalities are involved in these diseases. Scientists may be able to develop effective drug treatments for the various myopathies that would replace or restore any missing function and thus allow affected muscles to work normally.

RELATED ARTICLE: MDA's Search for a Treatment or Cure

MDA has continuously funded promising scientific investigations worldwide seeking treatments and cures for the myopathies. The Association makes every effort to support new experimental treatments whenever there is a reasonable scientific basis for doing so.

With the future discovery of the defective genes responsible for the inheritable myopathies, researchers will begin fashioning therapies aimed at providing normally functioning genes to compensate for the defective ones, as well as therapies to overcome the absence or abnormality of the proteins.

Under the auspices of MDA's Medical and Scientific Advisory committees, Association-backed scientists intensively search for the underlying causes and the potential therapies that might eliminate in part or whole the effects of these various inheritable and endocrine myopathies.

For further information about myopathies, call or write your local MDA, office, or write to MDA National Headquarters, 3300 East Sunrise Drive, Tucson, AZ 85718.


If your physician suspects that you or a member of your family may have one of the myopathies or another neuromuscular disease, call your local MDA office immediately to arrange for an appointment at the nearest MDA clinic.

A skilled specialist at one of MDA's 240 hospital-affiliated clinics nationwide can then confirm your doctor's initial diagnosis and make it possible for you to receive a wide variety of services. These range from medical care to recreational outings. Physical and occupational therapy evaluations are provided through MDA clinics to help maintain the strength that may be lost as a result of myopathies.

Accurate diagnosis of these diseases is extremely important so the best available care can be provided as quickly as possible. Many of the symptoms of these conditions can be alleviated with the expert medical management available at MDA clinics.

For a detailed description of MDA services, please contact your local MDA office and request a copy of the pamphlet, MDA Services for the Individual, Family and Community.

RELATED ARTICLE: MDA's Purpose and Programs

The Muscular Dystrophy Association fights 40 neuromuscular diseases through an unparalleled worldwide research effort, a nationwide program of medical services, and far-reaching professional and public health education. Individual MDA research grants to investigators in the United States and abroad number close to 500. The Association's Medical Advisory and Scientific Advisory committees review projects that will increase knowledge in the neuromuscular field and may lead to treatments or cures for muscular dystrophy and related disorders. MDA's Task Force on Genetics oversees studies of all aspects of genetic defects implicated directly or indirectly in neuromuscular diseases. Through MDA's patient services program, comprehensive medical services are furnished to children and adults with neuromuscular diseases at some 240 MDA hospital-affiliated clinics and through the Association's chapters. The following disease entitles are included in MDA's program.

MUSCULAR DYSTROPHIES Myotonic dystrophy (Steinert's disease) Duchenne (pseudohypertrophic)

muscular dystrophy Becker muscular dystrophy Limb-girdle muscular dystrophy Facioscapulohumeral (Landouzy-Dejerine)

muscular dystrophy Congenital muscular dystrophy Oculopharyngeal muscular dystrophy Distal muscular dystrophy Emery-Dreifuss muscular dystrophy

MOTOR NEURON DISEASES Amyotrophic lateral sclerrosis (ALS) Infantile progressive spinal muscular atrophy

(Type 1, Werdnig-Hoffmann disease) Intermediate spinal muscular atrophy

(Type 2) Juvenile spinal muscular atrophy

(Type 3, Kugelberg-Welander disease) Adult spinal muscular atrophy

(Aran-Duchenne type)

INFLAMMATORY MYOPATHIES Polymyositis Dermatomyositis

DISEASES OF NEUROMUSCULAR JUNCTION Myasthenia gravis Lambert-Eaton (myasthenic) syndrome

DISEASE OF PERIPHERAL NERVE Peroneal muscular atrophy

(Charcot-Marie-Tooth disease) Friedreich's ataxia Dejerine-Sottas disease

METABOLIC DISEASES OF MUSCLE Phosphorylase deficiency

(McArdle's disease) Acid maltase deficiency

(Pompe's disease) Phosphofructokinase deficiency

(Tarui's disease) Debrancher enzyme deficiency

(Cori's or Forbes' disease) Mitonchondrial myopathy Carnitine deficiency Carnitine palmityl transferase deficiency Phosphoglycerate kinase deficiency Phosphoglycerate mutase deficiency Lactate dehydrogenase deficiency Myoadenylate deaminase deficiency

MYOPATHIES DUE TO ENDOCRINE ABNORMALITIES Hyperthyroid myopathy Hypothyroid myopathy

OTHER MYOPATHIES Myotonia congenita Paramyotonia congenita Central core disease Nemaline myopathy Myotubular myopathy Periodic paralysis
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Publication:Pamphlet by: Muscular Dystrophy Association
Article Type:Pamphlet
Date:Feb 1, 1993
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