The FAIR Foundation is dedicated to fair and equitable distributions of Nation Institutes of Health (NIH) research funds for all diseases, including the sixteen that kill more Americans than AIDS.

Muscular Dystrophy's 9 Major Groups and Definitions

The disorders are classified by the extent and distribution of muscle weakness, age of onset, rate of progression, severity of symptoms, and family history (including any pattern of inheritance). Although some forms of MD become apparent in infancy or childhood, others may not appear until middle age or later. Overall, incidence rates and severity vary, but each of the dystrophies causes progressive skeletal muscle deterioration, and some types affect cardiac muscle.

There are four forms of MD that begin in childhood:

Duchenne MD is the most common childhood form of MD, as well as the most common of all the muscular dystrophies overall, accounting for approximately 50 percent of all cases. It affects approximately one in 3,500 male births. Because inheritance is X-linked recessive (caused by a mutation on the X, or sex, chromosome), Duchenne MD primarily affects boys, although girls and women who carry the defective gene may show some symptoms. About one-third of the cases reflect new mutations and the rest run in families. Sisters of boys with Duchenne MD have a 50 percent chance of carrying the defective gene.

Duchenne MD usually becomes apparent when an affected child begins to walk. Progressive weakness and muscle wasting (a decrease in muscle strength and size) caused by degenerating muscle fibers begins in the upper legs and pelvis before spreading into the upper arms. Other symptoms include loss of some reflexes, a waddling gait, frequent falls and clumsiness (especially when running), difficulty when rising from a sitting or lying position or when climbing stairs, changes to overall posture, impaired breathing, lung weakness, and cardiomyopathy (heart muscle weakness that interferes with pumping ability). Many children are unable to run or jump. The wasting muscles, in particular the calf muscle (and, less commonly, muscles in the buttocks, shoulders, and arms), may be enlarged by an accumulation of fat and connective tissue, causing them to look larger and healthier than they actually are (called pseudohypertrophy). As the disease progresses, the muscles in the diaphragm that assist in breathing and coughing may weaken. Patients may experience breathing difficulties, respiratory infections, and swallowing problems. Bone thinning and scoliosis (curving of the spine) are common. Some children are mildly mentally impaired. Between ages 3 and 6, children may show brief periods of physical improvement followed by progressive muscle degeneration. Children with Duchenne MD are typically wheelchair-bound by age 12 and usually die in their late teens or early twenties from progressive weakness of the heart muscle, respiratory complications, or infection.

Duchenne MD results from an absence of the muscle protein dystrophin. And blood tests of children with Duchenne MD show an abnormally high level of creatine kinase, which is apparent from birth.

A rare, autosomal recessive form of MD is seen primarily in the Middle East and North Africa. The disease is clinically similar to Duchenne but is less severe and progresses more slowly. Onset of muscle weakness is typically between ages 5 and 10. Most patients lose the ability to walk in their early twenties, and most die in their forties from cardiac or respiratory complications.

Becker MD is less severe than but closely related to Duchenne MD. Persons with Becker MD have partial but insufficient function of the protein dystrophin. The disorder usually appears around age 11 but may occur as late as age 25, and patients generally live into middle age or later. The rate of progressive, symmetric (on both sides of the body) muscle atrophy and weakness varies greatly among affected individuals. Many patients walk well into their thirties, while others are unable to walk past their teens. Some affected individuals never need to use a wheelchair. As in Duchenne MD, muscle weakness in Becker MD is typically noticed first in the upper arms and shoulders, upper legs, and pelvis.

Early symptoms of Becker MD include walking on one's toes, frequent falls, and difficulty rising from the floor. Calf muscles may appear large and healthy as deteriorating muscle fibers are replaced by fat, and muscle activity may cause cramps in some people. Cardiac and mental impairments are not as severe as in Duchenne MD.

Congenital MD refers to a group of autosomal recessive muscular dystrophies that are either present at birth or become evident before age 2. They affect both boys and girls. The degree and progression of muscle weakness and degeneration vary with the type of disorder. Weakness may be first noted when children fail to meet landmarks in motor function and muscle control. Muscle degeneration may be mild or severe and is restricted primarily to skeletal muscle. The majority of patients are unable to sit or stand without support, and some affected children may never learn to walk. There are three groups of congenital MD:

merosin-negative disorders, where the protein merosin (found in the connective tissue that surrounds muscle fibers) is missing;
merosin-positive disorders, in which merosin is present but other needed proteins are missing; and
neuronal migration disorders, in which very early in the development of the fetal nervous system the migration of nerve cells (neurons) to their proper location is disrupted.

Defects in the protein merosin cause nearly half of all cases of congenital MD.

Patients with congenital MD may develop contractures (chronic shortening of muscles or tendons around joints, which prevents the joints from moving freely), scoliosis, respiratory and swallowing difficulties, and foot deformities. Some patients have normal intellectual development while others become severely impaired. Weakness in diaphragm muscles may lead to respiratory failure. Congenital MD may also affect the central nervous system, causing vision and speech problems, seizures, and structural changes in the brain. Some children with the disorders die in infancy while others may live into adulthood with only minimal disability.

Emery-Dreifuss MD primarily affects boys. The disorder has two forms: one is X-linked recessive and the other is autosomal dominant.

Onset of Emery-Dreifuss MD is usually apparent by age 10, but symptoms can appear as late as the mid-twenties. This disease causes slow but progressive wasting of the upper arm and lower leg muscles and symmetric weakness. Contractures in the spine, ankles, knees, elbows, and back of the neck usually precede significant muscle weakness, which is less severe than in Duchenne MD. Contractures may cause elbows to become locked in a flexed position. The entire spine may become rigid as the disease progresses. Other symptoms include shoulder deterioration, toe-walking, and mild facial weakness. Serum creatine kinase levels may be moderately elevated. Nearly all Emery-Dreifuss MD patients have some form of heart problem by age 30, often requiring a pacemaker or other assistive device. Female carriers of the disorder often have cardiac complications without muscle weakness. Patients often die in mid-adulthood from progressive pulmonary or cardiac failure.

Youth/adolescent-onset muscular dystrophies are classified two ways:

Facioscapulohumeral MD (FSHD) initially affects muscles of the face (facio), shoulders (scapulo), and upper arms (humera) with progressive weakness. Also known as Landouzy-Dejerine disease, this third most common form of MD is an autosomal dominant disorder. Life expectancy is normal, but some individuals become severely disabled. Disease progression is typically very slow, with intermittent spurts of rapid muscle deterioration. Onset is usually in the teenage years but may occur as late as age 40. Muscles around the eyes and mouth are often affected first, followed by weakness around the lower shoulders and chest. A particular pattern of muscle wasting causes the shoulders to appear to be slanted and the shoulder blades to appear winged. Muscles in the lower extremities may also become weakened. Reflexes are impaired only at the biceps and triceps. Changes in facial appearance may include the development of a crooked smile, a pouting look, flattened facial features, or a mask-like appearance. Some patients cannot pucker their lips or whistle and may have difficulty swallowing, chewing, or speaking. Other symptoms may include hearing loss (particularly at high frequencies) and lordosis, an abnormal swayback curve in the spine. Contractures are rare. Some FSHD patients feel severe pain in the affected limb. Cardiac muscles are not affected, and the pelvic girdle is rarely significantly involved. An infant-onset form of FSHD can also cause retinal disease and some hearing loss.

Limb-girdle MD refers to more than a dozen inherited conditions marked by progressive loss of muscle bulk and symmetrical weakening of voluntary muscles, primarily those in the shoulders and around the hips. At least three forms of autosomal dominant limb-girdle MD (known as type 1) and eight forms of autosomal recessive limb-girdle MD (known as type 2) have been identified. Some autosomal recessive forms of the disorder are now known to be due to a deficiency of any of four dystrophin-glycoprotein complex proteins called the sarcoglycans.

The recessive limb-girdle muscular dystrophies occur more frequently than the dominant forms, usually begin in childhood or the teenage years, and show dramatically increased levels of serum creatine kinase. The dominant limb-girdle muscular dystrophies usually begin in adulthood. In general, the earlier the clinical signs appear, the more rapid the rate of disease progression. Limb-girdle MD affects both males and females. Some forms of the disease progress rapidly, resulting in serious muscle damage and loss of the ability to walk, while others advance very slowly over many years and cause minimal disability, allowing a normal life expectancy. In some cases, the disorder appears to halt temporarily, but symptoms then resume.

Weakness is typically noticed first around the hips before spreading to the shoulders, legs, and neck. Patients develop a waddling gait and have difficulty when rising from chairs, climbing stairs, or carrying heavy objects. Patients fall frequently and are unable to run. Contractures at the elbows and knees are rare but patients may develop contractures in the back muscles, which gives them the appearance of a rigid spine. Proximal reflexes (closest to the center of the body) are often impaired. Some patients also experience cardiomyopathy and respiratory complications. Intelligence remains normal. Most persons with limb-girdle MD become severely disabled within 20 years of disease onset.

There are three forms of MD that usually begin in adulthood.

Distal MD, also called distal myopathy, describes a group of at least six specific muscle diseases that primarily affect distal muscles (those farthest away from the shoulders and hips) in the forearms, hands, lower legs, and feet. Distal dystrophies are typically less severe, progress more slowly, and involve fewer muscles than other forms of MD, although they can spread to other muscles. Distal MD can affect the heart and respiratory muscles, and patients may eventually require the use of a ventilator. Patients may not be able to perform fine hand movement and have difficulty extending the fingers. As leg muscles become affected, walking and climbing stairs become difficult and some patients may be unable to hop or stand on their heels. Onset of distal MD, which affects both men and women, is typically between the ages of 40 and 60 years. In one form of distal MD, a muscle membrane protein complex called dysferlin is known to be lacking.

Although distal MD is primarily an autosomal dominant disorder, autosomal recessive forms have been reported in young adults. Symptoms are similar to those of Duchenne MD but with a different pattern of muscle damage. An infantile-onset form of autosomal recessive distal MD has also been reported. Slow but progressive weakness is often first noticed around age 1, when the child begins to walk, and continues to progress very slowly throughout adult life.

Myotonic MD, also known as Steinert's disease and dystrophia myotonica, may be the most common adult form of MD. Myotonia, or an inability to relax muscles following a sudden contraction, is found only in this form of MD. People with myotonic MD can live a long life, with variable but slowly progressive disability. Typical disease onset is between ages 20 and 30, but it may develop earlier. Myotonic MD affects the central nervous system and other body systems, including the heart, adrenal glands and thyroid, eyes, and gastrointestinal tract. Muscles in the face and the front of the neck are usually first to show weakness and may produce a haggard, "hatchet" face and a thin, swan-like neck. Wasting and weakness noticeably affect forearm muscles. Other symptoms include cardiac complications, difficulty swallowing, droopy eyelids (called ptosis), cataracts, poor vision, early frontal baldness, weight loss, impotence, testicular atrophy, mild mental impairment, and increased sweating. Patients may also feel drowsy and have an excess need to sleep.

This autosomal dominant disease affects both men and women. Females may have irregular menstrual periods and may be infertile. The disease occurs earlier and is more severe in successive generations. A childhood form of myotonic MD may become apparent between ages 5 and 10. Symptoms include general muscle weakness (particularly in the face and distal muscles), lack of muscle tone, and mental impairment.

An expectant mother with myotonic MD can give birth to an infant with a rare congenital form of the disorder. Symptoms at birth may include difficulty swallowing or sucking, impaired breathing, absence of reflexes, skeletal deformities (such as club feet), and noticeable muscle weakness, especially in the face. Children with congenital myotonic MD may also experience mental impairment and delayed motor development. This severe infantile form of myotonic MD occurs almost exclusively in children who have inherited the defective gene from their mother, who may not know she is a carrier of the disease.

The inherited gene defect that causes myotonic MD is an abnormally long repetition of a three-letter "word" in the genetic code. In unaffected people, the word is repeated a number of times, but in people with myotonic MD, it is repeated many more times. This triplet repeat gets longer with each successive generation. The triplet repeat mechanism has now been implicated in at least 15 other disorders, including Huntington's disease and the spinocerebellar ataxias.

Oculopharyngeal MD (OPMD) generally begins in a person's forties or fifties and affects both men and women. In the United States, the disease is most common in families of French-Canadian descent and among Hispanic residents of northern New Mexico. Patients first report drooping eyelids, followed by weakness in the facial muscles and pharyngeal muscles in the throat, causing difficulty swallowing. The tongue may atrophy and changes to the voice may occur. Eyelids may droop so dramatically that some patients compensate by tilting back their heads. Patients may have double vision and problems with upper gaze, and others may have retinitis pigmentosa (progressive degeneration of the retina that affects night vision and peripheral vision) and cardiac irregularities. Muscle weakness and wasting in the neck and shoulder region is common. Limb muscles may also be affected. Persons with OPMD may find it difficult to walk, climb stairs, kneel, or bend. Those persons most severely affected will eventually lose the ability to walk.