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The Lancet Neurology. Limb-girdle muscular dystrophy. Duchenne muscular dystrophy DMD. Muscular Dystrophy Association. Bonow RO, et al. Neurological disorders and cardiovascular disease. There are nine major groups of the muscular dystrophies. 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. Duchenne MD is the most common childhood form of MD, as well as the most common of the muscular dystrophies overall, accounting for approximately 50 percent of all cases.
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 during the toddler years, sometimes soon after 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. Many children are unable to run or jump. The wasting muscles, in particular the calf muscles 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. Affected individuals may experience breathing difficulties, respiratory infections, and swallowing problems. Bone thinning and scoliosis curving of the spine are common. Some affected children have varying degrees of cognitive and behavioral impairments. Between ages 3 and 6, children may show brief periods of physical improvement followed later on by progressive muscle degeneration.
Children with Duchenne MD typically lose the ability to walk by early adolescence. Without aggressive care, they usually die in their late teens or early twenties from progressive weakness of the heart muscle, respiratory complications, or infection. However, improvements in multidisciplinary care have extended the life expectancy and improved the quality of life significantly for these children; numerous individuals with Duchenne muscular dystrophy now survive into their 30s, and some even into their 40s.
Duchenne MD results from an absence of the muscle protein dystrophin. Dystrophin is a protein found in muscle that helps muscles stay healthy and strong.
Blood tests of children with Duchenne MD show an abnormally high level of creatine kinase; this finding is apparent from birth.
People 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 affected individuals 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 individuals are able to walk until they are in their mid-thirties or later, 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 complications are not as consistently present in Becker MD compared to Duchenne MD, but may be as severe in some cases.
Cognitive and behavioral impairments are not as common or severe as in Duchenne MD, but they do occur. 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 individuals are unable to sit or stand without support, and some affected children may never learn to walk. There are three groups of congenital MD:. People 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 individuals 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. 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, including the proximal ones later in the course of the disease.
Distal MD can affect the heart and respiratory muscles, and idividuals may eventually require the use of a ventilator. Affected individuals 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 people 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. 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 people with Emery-Dreifuss MD 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. Affected individuals often die in mid-adulthood from progressive pulmonary or cardiac failure.
In some cases, the cardiac symptoms may be the earliest and most significant symptom of the disease, and may appear years before muscle weakness does.
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.
Most individuals have a normal life span, 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 early as childhood or as late as age One hallmark of FSHD is that it commonly causes asymmetric weakness.
Muscles around the eyes and mouth are often affected first, followed by weakness around the shoulders, chest, and upper arms. 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 diminished, typically in the same distribution as the weakness. Changes in facial appearance may include the development of a crooked smile, a pouting look, flattened facial features, or a mask-like appearance.
Some individuals cannot pucker their lips or whistle and may have difficulty swallowing, chewing, or speaking. In some individuals, muscle weakness can spread to the diaphragm, causing respiratory problems. Other symptoms may include hearing loss particularly at high frequencies and lordosis , an abnormal swayback curve in the spine. Contractures are rare. Some people with FSHD feel severe pain in the affected limb.
Cardiac muscles are not usually affected, and significant weakness of the pelvic girdle is less common than in other forms of MD.
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