Muscular Dystrophy

There are nine major groups of muscular dystrophies. The disorders are classified by the:

• Extent and distribution of muscle weakness
• Age of onset
• Rate of progression
• Severity of symptoms
• 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 muscular dystrophy 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 chromosome), Duchenne MD primarily affects males, although females who carry the defective gene may show some symptoms. About one-third of the cases reflect new mutations, and the rest run in families. Female siblings of male children with Duchenne MD have a 50 percent chance of carrying the defective gene. The disorder gets its name from the French neurologist Guillaume Duchenne. 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. 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 getting up from a sitting position or when climbing stairs
• Changes to overall posture
• Impaired breathing
• Lung weakness
• 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 (pseudohypertrophy). As the disease progresses, the muscles in the diaphragm that assist in breathing and coughing may weaken. Individuals may experience breathing difficulties, respiratory infections and swallowing problems. Bone thinning and scoliosis (curving of the spine) are common. Some children have varying degrees of cognitive and behavioral impairments.

Between ages three and six, children may show brief periods of physical improvement followed by progressive muscle degeneration later. Children with Duchenne MD typically lose the ability to walk by early adolescence. Improvements in multidisciplinary care have extended the life expectancy and improved the quality of life significantly for children with Duchenne MD. Numerous individuals survive into their 30s, and some even into their 40s.

Becker muscular dystrophy is less severe than but closely related to Duchenne MD. 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-30s 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
• 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 muscular dystrophy refers to a group of autosomal recessive muscular dystrophies that are either present at birth or become evident before age two. 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:

1. Merosin-negative disorders, in which the protein merosin (found in the connective tissue that surrounds muscle fibers) is missing
2. Merosin-positive disorders, in which merosin is present but other necessary proteins are missing
3. 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.

People with congenital MD may develop:

• Contractures (chronic shortening of muscles or tendons around joints, preventing them from moving freely)
• Scoliosis (curved spine)
• Breathing and swallowing difficulties
• Feet problems

The intellectual development of some children progresses as expected, 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.

Distal muscular dystrophy (also known as 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 individuals may eventually require the use of a ventilator. They 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 males and females, 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 one, when the child begins to walk, and continues to progress very slowly throughout adult life.

Emery-Dreifuss muscular dystrophy primarily affects male children. 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-20s. This disease causes slow yet 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
• Walking on one's toes
• 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. 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 muscular dystrophy (FSHD) initially affects muscles of the face (facio), shoulders (scapulo) and upper arms (humera) with progressive weakness. Also known as Landouzy-Dejerine disease, this is the third most common form of MD and is characterized as an autosomal dominant disorder. Most people have a normal life span, but some become severely disabled.

Disease progression is typically very slow, with intermittent spurts of rapid muscle deterioration. Onset is usually in the teens but may occur as early as childhood or as late as age 40. 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. Muscle weakness can also spread to the diaphragm, causing respiratory problems.

Other symptoms may include:

• Hearing loss (particularly at high frequencies)
• Lordosis (inward curve of the lumbar 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 pelvis is less common than in other forms of MD. An infant-onset form of FSHD can cause retinal disease and some hearing loss.

Limb-girdle muscular dystrophy (LGMD) refers to more than 20 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 five forms of autosomal dominant limb-girdle MD (known as type 1) and 17 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. Deficiencies in dystroglycan, classically associated with congenital muscular dystrophies, may also cause LGMD.

The recessive LGMDs occur more frequently than the dominant forms, usually starting in childhood or the teens, and show dramatically increased levels of serum creatine kinase. The dominant LGMDs 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 progression then resumes.

The pattern of muscle weakness is similar to that of Duchenne MD and Becker MD. Weakness is typically noticed first around the hips before spreading to the shoulders, legs and neck. Individuals develop a waddling gait and have difficulty when rising from chairs, climbing stairs or carrying heavy objects. They fall frequently and are unable to run. Contractures at the elbows and knees are rare, but individuals 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 individuals also experience cardiomyopathy and respiratory complications, depending in part on the specific subtype. Intelligence remains in most cases, though exceptions do occur. Many individuals with limb-girdle MD become severely disabled within 20 years of disease onset.

Myotonic dystrophy (DM1), also known as Steinert's disease and dystrophia myotonica, is another common form of MD. Myotonia, or the inability to relax muscles following a sudden contraction, is found only in this form of MD, but is also found in other non-dystrophic muscle diseases. People with DM1 can live a long life, with variable but slowly progressive disability. Typical disease onset is between ages 20 and 30, but childhood onset and congenital onset are well documented. Muscles in the face and the front of the neck are usually first to show weakness and may produce hollow temples, drooping facial skin and a thin neck. Wasting and weakness noticeably affect forearm muscles. DM1 affects the central nervous system and other body systems, including the heart, adrenal glands and thyroid, eyes and gastrointestinal tract.

Other symptoms include:

• Cardiac complications
• Difficulty swallowing
• Droopy eyelids (ptosis)
• Cataracts
• Poor vision
• Early frontal baldness
• Weight loss
• Impotence
• Testicular atrophy
• Mild mental impairment
• Increased sweating

​​​​​​Individuals may feel drowsy and have an excessive need for sleep. There is a second form known as myotonic dystrophy type 2 (DM2) that is similar to the classic form, but usually affects proximal muscles more significantly.

This autosomal dominant disease affects both males and females. Females may have irregular menstrual periods and are sometimes infertile. The disease may occur earlier and be more severe in successive generations. A childhood-onset form of myotonic MD may become apparent between ages five and 10. Symptoms include:

• General muscle weakness (particularly in the face and muscles farthest away from center of body)
• Lack of muscle tone
• Cognitive impairment

A female with DM1 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 and contractures (club feet)
• Muscle weakness, especially in the face

Children with congenital myotonic MD may also experience cognitive 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 female parent, whose symptoms may be so mild that they are sometimes not aware of the disease.

The inherited gene defect that causes DM1 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 DM1, 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 muscular dystrophy (OPMD) generally begins in the 40s and 50s and affects both males and females. In the U.S., the disease is most common in families of French-Canadian descent as well as among Hispanic residents of northern New Mexico. People first report drooping eyelids, followed by weakness in the facial muscles and pharyngeal muscles in the throat that cause problems with swallowing. The tongue may atrophy and changes to the voice may occur. Eyelids may droop so dramatically that some individuals compensate by tilting back their heads. Affected individuals may have:

• Double vision
• Problems with upper gaze
• Retinitis pigmentosa (progressive degeneration of the retina that affects night vision and peripheral vision)
• Cardiac irregularities

Muscle weakness and wasting in the neck and shoulder region is common. Limb muscles may also be affected. People with OPMD may find it difficult to walk, climb stairs, kneel or bend. The most severely affected will eventually lose the ability to walk.

Other types of neuromuscular disorders include:

• Amyotrophic lateral sclerosis (ALS)
• Charcot-Marie-Tooth disease
• Multiple sclerosis
• Muscular dystrophy
• Myasthenia gravis
• Myopathy
• Myositis, including polymyositis and dermatomyositis
• Peripheral neuropathy

There are many other heritable diseases that affect muscles, nerves or the neuromuscular junction. Diseases like inflammatory myopathy, progressive muscle weakness and cardiomyopathy (heart muscle weakness that interferes with pumping ability) may produce symptoms that are very similar to those found in some forms of MD, but they are caused by different genetic defects. Disorders with symptoms similar to MD include:

• Congenital myopathy
• Spinal muscular atrophy
• Congenital myasthenic syndromes

The sharing of symptoms among multiple neuromuscular diseases, and the prevalence of sporadic cases in families not previously affected by MD, often makes it difficult for people with MD to obtain a quick diagnosis. Some individuals may have signs of MD but carry none of the currently recognized genetic mutations.

Neuromuscular disorders are caused by a range of deficiencies and disorders, including:

• Genetic mutation
• Viral infection
• Autoimmune disorder
• Hormonal disorder
• Metabolic disorder
• Dietary deficiency
• Certain drugs and poisons

Most cases of MD are caused by gene mutations (changes in the DNA sequence) that affect muscle proteins.

The mutations are usually inherited, but in some cases they occur spontaneously. These spontaneous mutations can then be inherited by an affected person’s offspring.

There are three different inheritance patterns for most forms of MD. When a mutation that causes MD is inherited by a parent with the condition, this is known as autosomal dominant inheritance.

In contrast, for most autosomal recessive conditions, the gene mutation must be inherited from both parents. Both matching genes must include a mutation to cause the disease.

However, the inheritance pattern for many types of MD is called X-linked recessive, meaning that the genetic change is passed from one generation to the next through the X chromosome.

Girls and women have two X chromosomes (XX), while boys and men have one X and one Y chromosome (XY). This pattern is the reason certain types of MD, whose mutations are on the X chromosome, are more common in males than in females.

• If a female has one X chromosome with the genetic mutation and one X chromosome without, she may not have symptoms or may have milder MD than males have. She is called a carrier because she has the genetic mutation and can pass it on to her children.
• Because males have only one X chromosome, if they have the genetic mutation, they will usually have symptoms of MD or more severe MD symptoms than females do.

Hundreds of genes are involved in making proteins that affect muscles. Each form of MD is caused by a genetic mutation that is unique to that type. For instance:

• Duchenne MD results from a genetic mutation that leads to a lack of dystrophin, a protein that helps strengthen muscle fibers and protect them from injury. It can be inherited in an X-linked recessive manner.
• Myotonic MD is caused by an abnormal expansion of certain DNA sequences on one of two different genes. Most people may have around 40 repeats of a certain DNA code in their gene, but people with myotonic MD have 4,000 or more repeats. These repeats cause errors in the “instructions” for making muscle proteins, meaning the body may not make enough of the protein or may not make usable forms of the protein. In some cases, the instructions themselves build up to high levels; this buildup causes problems with the protein. Myotonic MD can be inherited in an autosomal dominant manner.

Many neuromuscular disorders are inherited, passed from generation to generation through genetic code, though sometimes they are a result of spontaneous gene mutation. There are links to NDs and immune system disorders, but each condition has its unique causes.

All of the muscular dystrophies (MDs) are inherited and involve a gene mutation or defect. The body's cells don't work properly when a protein is altered or produced in insufficient quantity (or sometimes missing completely). Many cases of MD occur from spontaneous mutations that are not found in the genes of either parent, and this can be passed to the next generation.

Genes are like blueprints; they contain coded messages that determine a person's characteristics or traits. They are arranged along 23 rod-like pairs of chromosomes with one-half of each pair being inherited from each parent. Each half of a chromosome pair is similar to the other, except for one pair, which determines the sex of the individual. Muscular dystrophies can be inherited in three ways:

1. Autosomal dominant inheritance occurs when a child receives a normal gene from one parent and a defective gene from the other parent. Autosomal means the genetic mutation can occur on any of the 22 non-sex chromosomes in each of the body's cells. Dominant means only one parent needs to pass along the abnormal gene in order to produce the disorder. In families where one parent carries a defective gene, each child has a 50 percent chance of inheriting the gene and therefore the disorder. Males and females are equally at risk, and the severity of the disorder can differ from person to person.
2. Autosomal recessive inheritance means that both parents must carry and pass on the faulty gene. The parents each have one defective gene but are not affected by the disorder. Children in these families have a 25 percent chance of inheriting both copies of the defective gene and a 50 percent chance of inheriting one gene and therefore becoming a carrier, able to pass along the defect to their children. Children of either sex can be affected by this pattern of inheritance.
3. X-linked (or sex-linked) recessive inheritance occurs when the female parent carries the affected gene on one of two X chromosomes and passes it to the male child (males always inherit an X chromosome from their female parent and a Y chromosome from their male parent, while females inherit an X chromosome from each parent). Male children of carrier female parents have a 50 percent chance of inheriting the disorder. Female children also have a 50 percent chance of inheriting the defective gene but usually are not affected, since the healthy X chromosome they receive from their male parent can offset the faulty one received from their female parent. Affected male parents cannot pass an X-linked disorder to their male children, but their female children will be carriers of that disorder. Carrier females occasionally can exhibit milder symptoms of MD.

Muscle response and neuronal-electrical activity can be tested using electromyography (EMG). These diagnostic tools stimulate muscles and help neurologists detect abnormalities in responses.

Various laboratory tests may be used to confirm the diagnosis of muscular dystrophy (MD), including:

• Blood and urine tests to detect defective genes and help identify specific neuromuscular disorders.
• Exercise tests to detect elevated rates of certain chemicals following exercise and to determine the nature of the MD or other muscle disorder.
• Genetic testing to look for genes known to either cause or be associated with inherited muscle disease. DNA analysis and enzyme assays can confirm the diagnosis of certain neuromuscular diseases, including MD. Genetic linkage studies can identify whether a specific genetic marker on a chromosome and a disease are inherited together. They are particularly useful in studying families with members in different generations who are affected. Advances in genetic testing include whole exome and whole genome sequencing, which will enable people to have all of their genes screened at once for disease-causing mutations, rather than have just one gene or several genes tested at a time. 
• Genetic counseling to help parents who have a family history of MD determine if they are carrying one of the mutated genes that cause the disorder. Two tests can be used to help expectant parents find out if their child is affected.
• Amniocentesis at 14–16 weeks of pregnancy to test a sample of the amniotic fluid in the womb for genetic defects (the fluid and the fetus have the same DNA).
• Chorionic villus sampling (CVS) to test a very small sample of the placenta during early pregnancy.
• Diagnostic imaging can help determine the specific nature of a disease or condition. Magnetic resonance imaging (MRI) is used to examine muscle quality, any atrophy or abnormalities in size, and fatty replacement of muscle tissue, as well as to monitor disease progression. Other forms of diagnostic imaging for MD:
  • Phosphorus magnetic resonance spectroscopy measures cellular response to exercise and the amount of energy available to muscle fiber.
  • Ultrasound imaging (also known as sonography) uses high-frequency sound waves to obtain images inside the body.
• Muscle biopsies to monitor the course of disease and treatment effectiveness. Muscle biopsies can sometimes also assist in carrier testing.
• Immunofluorescence testing to detect specific proteins such as dystrophin within muscle fibers.
• Electron microscopy to identify changes in subcellular components of muscle fibers. Electron microscopy also can identify changes that characterize cell death, mutations in muscle cell mitochondria, and an increase in connective tissue seen in muscle diseases such as MD.
• Neurophysiology studies to identify physical and/or chemical changes in the nervous system.
• Nerve conduction velocity to measure the speed and strength with which an electrical signal travels along a nerve and can help determine whether nerve damage is present.
• Repetitive stimulation to assess the function of the neuromuscular junction by electrically stimulating a motor nerve several times in a row.
• Electromyography (EMG) to record muscle fiber and motor unit activity. Results may reveal electrical activity characteristic of MD or other neuromuscular disorders.
   

Symptoms of neuromuscular disorders include muscular weakness, wastage, cramps, spasticity (stiffness), which later causes joint or skeletal deformities, and muscle pain. Additional symptoms include breathing and swallowing difficulties.

All forms of muscular dystrophy (MD) grow worse as muscles progressively degenerate and weaken. Many individuals eventually lose the ability to walk.

Some types of MD also affect the:

• Heart
• Gastrointestinal system
• Endocrine glands
• Spine
• Eyes
• Brain
• Other organs

Respiratory and cardiac diseases may occur, and some people may develop a swallowing disorder. MD is not contagious and cannot be brought on by injury or activity.

Although MD can affect several body tissues and organs, it most prominently affects the integrity of muscle fibers. The disease causes:

• Muscle degeneration
• Progressive weakness
• Fiber death
• Fiber branching and splitting
• Phagocytosis (muscle fiber material is broken down and destroyed by scavenger cells)
• Chronic or permanent shortening of tendons and muscle

Also, overall muscle strength and tendon reflexes are usually lessened or lost due to replacement of muscle by connective tissue and fat.

There are many other heritable diseases that affect muscles, nerves or the neuromuscular junction. Diseases like inflammatory myopathy, progressive muscle weakness and cardiomyopathy (heart muscle weakness that interferes with pumping ability) may produce symptoms that are very similar to those found in some forms of MD, but they are caused by different genetic defects. Disorders with symptoms similar to MD include:

• Congenital myopathy
• Spinal muscular atrophy
• Congenital myasthenic syndromes

The sharing of symptoms among multiple neuromuscular diseases, and the prevalence of sporadic cases in families not previously affected by MD, often makes it difficult for people with MD to obtain a quick diagnosis. Some individuals may have signs of MD but carry none of the currently recognized genetic mutations.

Duchenne muscular dystrophy 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. 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 getting up from a sitting position or when climbing stairs
• Changes to overall posture
• Impaired breathing
• Lung weakness
• Cardiomyopathy

Becker muscular dystrophy is less severe than but closely related to Duchenne MD. 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-30s 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
• 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 muscular dystrophy refers to a group of autosomal recessive muscular dystrophies that are either present at birth or become evident before age two. 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.
People with congenital MD may develop:

• Contractures (chronic shortening of muscles or tendons around joints, preventing them from moving freely)
• Scoliosis (curved spine)
• Breathing and swallowing difficulties
• Feet problems

The intellectual development of some children progresses as expected, 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.

Distal muscular dystrophy (also known as 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 individuals may eventually require the use of a ventilator. They 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 males and females, 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 one, when the child begins to walk, and continues to progress very slowly throughout adult life.

Emery-Dreifuss muscular dystrophy primarily affects male children. 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-20s. This disease causes slow yet 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
• Walking on one's toes
• Mild facial weakness

Facioscapulohumeral muscular dystrophy (FSHD) initially affects muscles of the face (facio), shoulders (scapulo) and upper arms (humera) with progressive weakness. Also known as Landouzy-Dejerine disease, this is the third most common form of MD and is characterized as an autosomal dominant disorder. Most people have a normal life span, but some become severely disabled.

Disease progression is typically very slow, with intermittent spurts of rapid muscle deterioration. Onset is usually in the teens but may occur as early as childhood or as late as age 40. 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. Muscle weakness can also spread to the diaphragm, causing respiratory problems.

Other symptoms may include:

• Hearing loss (particularly at high frequencies)
• Lordosis (inward curve of the lumbar spine)

Limb-girdle muscular dystrophy (LGMD) refers to more than 20 inherited conditions marked by progressive loss of muscle bulk and symmetrical weakening of voluntary muscles, primarily those in the shoulders and around the hips. The pattern of muscle weakness is similar to that of Duchenne MD and Becker MD. Weakness is typically noticed first around the hips before spreading to the shoulders, legs and neck. Individuals develop a waddling gait and have difficulty when rising from chairs, climbing stairs or carrying heavy objects. They fall frequently and are unable to run. Contractures at the elbows and knees are rare but individuals 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 individuals also experience cardiomyopathy and respiratory complications, depending in part on the specific subtype. Intelligence remains in most cases, though exceptions do occur. Many individuals with limb-girdle MD become severely disabled within 20 years of disease onset.

Myotonic dystrophy (DM1), also known as Steinert's disease and dystrophia myotonica, is another common form of MD. Myotonia, or the inability to relax muscles following a sudden contraction, is found only in this form of MD, but is also found in other non-dystrophic muscle diseases.

Typical disease onset is between ages 20 and 30, but childhood onset and congenital onset are well documented. Muscles in the face and the front of the neck are usually first to show weakness and may produce hollow temples, drooping facial skin and a thin neck. Wasting and weakness noticeably affect forearm muscles. DM1 affects the central nervous system and other body systems, including the heart, adrenal glands and thyroid, eyes and gastrointestinal tract.

Other symptoms include:

• Cardiac complications
• Difficulty swallowing
• Droopy eyelids (ptosis)
• Cataracts
• Poor vision
• Early frontal baldness
• Weight loss
• Impotence
• Testicular atrophy
• Mild mental impairment
• Increased sweating

​​​​​​Individuals may feel drowsy and have an excessive need for sleep. There is a second form known as myotonic dystrophy type 2 (DM2) that is similar to the classic form, but usually affects proximal muscles more significantly.

Oculopharyngeal muscular dystrophy (OPMD) generally begins in the 40s and 50s and affects both males and females. People first report drooping eyelids, followed by weakness in the facial muscles and pharyngeal muscles in the throat that cause problems with swallowing. The tongue may atrophy and changes to the voice may occur. Eyelids may droop so dramatically that some individuals compensate by tilting back their heads. Affected individuals may have:

• Double vision
• Problems with upper gaze
• Retinitis pigmentosa (progressive degeneration of the retina that affects night vision and peripheral vision)
• Cardiac irregularities

Muscle weakness and wasting in the neck and shoulder region is common. Limb muscles may also be affected. People with OPMD may find it difficult to walk, climb stairs, kneel or bend. The most severely affected will eventually lose the ability to walk.

Neuromuscular disorders are determined through various tests that measure a body’s nerves ability to conduct electricity. Electromyography (EMG) tests can determine the health of a muscle. Additionally, doctors may use muscle biopsies, genetic testing and blood tests.

Various laboratory tests may be used to confirm the diagnosis of muscular dystrophy (MD), including:

• Blood and urine tests to detect defective genes and help identify specific neuromuscular disorders.
• Exercise tests to detect elevated rates of certain chemicals following exercise and are used to determine the nature of the MD or other muscle disorder.
• Genetic testing to look for genes known to either cause or be associated with inherited muscle disease. DNA analysis and enzyme assays can confirm the diagnosis of certain neuromuscular diseases, including MD. Genetic linkage studies can identify whether a specific genetic marker on a chromosome and a disease are inherited together. They are particularly useful in studying families with members in different generations who are affected. Advances in genetic testing include whole exome and whole genome sequencing, which will enable people to have all of their genes screened at once for disease-causing mutations, rather than have just one gene or several genes tested at a time. 
• Genetic counseling to help parents who have a family history of MD determine if they are carrying one of the mutated genes that cause the disorder. Two tests can be used to help expectant parents find out if their child is affected.
• Amniocentesis at 14–16 weeks of pregnancy to test a sample of the amniotic fluid in the womb for genetic defects (the fluid and the fetus have the same DNA).
• Chorionic villus sampling (CVS) to test a very small sample of the placenta during early pregnancy.
  Diagnostic imaging can help determine the specific nature of a disease or condition. Magnetic resonance imaging (MRI) is used to examine muscle quality, any atrophy or abnormalities in size, and fatty replacement of muscle tissue, as well as to monitor disease progression. Other forms of diagnostic imaging for MD:
  • Phosphorus magnetic resonance spectroscopy measures cellular response to exercise and the amount of energy available to muscle fiber.
  • Ultrasound imaging (also known as sonography) uses high-frequency sound waves to obtain images inside the body.
• Muscle biopsies to monitor the course of disease and treatment effectiveness. Muscle biopsies can sometimes also assist in carrier testing.
• Immunofluorescence testing to detect specific proteins such as dystrophin within muscle fibers.
• Electron microscopy to identify changes in subcellular components of muscle fibers. Electron microscopy also can identify changes that characterize cell death, mutations in muscle cell mitochondria, and an increase in connective tissue seen in muscle diseases such as MD.
• Neurophysiology studies to identify physical and/or chemical changes in the nervous system.
• Nerve conduction velocity to measure the speed and strength with which an electrical signal travels along a nerve and can help determine whether nerve damage is present.
• Repetitive stimulation to assess the function of the neuromuscular junction by electrically stimulating a motor nerve several times in a row.
• Electromyography (EMG) to record muscle fiber and motor unit activity. Results may reveal electrical activity characteristic of MD or other neuromuscular disorders.

Medical therapy, immunosuppressive drugs, assistive devices and pain management are all common treatment methods for neuromuscular disorders. Filtering out antibodies that are associated with the disease from the blood is an alternative treatment called apheresis.

Available treatments for muscular dystrophy (MD) are aimed at keeping people independent for as long as possible and to prevent complications that can arise from weakness, reduced mobility and cardiac and respiratory difficulties. 

Treatment may involve a combination of approaches, including physical therapy, drug therapy and surgery.

• Assisted ventilation is often needed to treat respiratory muscle weakness that accompanies many forms of MD, especially in the later stages.
• Drug therapy may be prescribed to delay muscle degeneration.
  • The U.S. Food and Drug Administration (FDA) has approved injections of the drugs golodirsen and viltolarsen to treat individuals with Duchenne muscular dystrophy (DMD) who have a confirmed mutation of the dystrophin gene that is amenable to exon 53 skipping. The FDA approved injection of the drug casimersen to treat individuals who have a confirmed mutation of the DMD gene that is amenable to exon 45 skipping. 
  • The FDA also approved three applications of fingolimod (Gilenya) to treat the relapsing form of MS in adults. Corticosteroids, such as prednisone, can slow the rate of muscle deterioration in Duchenne MD and help children retain strength to prolong independent walking by as much as several years. However, these medicines have side effects such as weight gain, facial changes, loss of linear (height) growth, and bone fragility that can be especially troubling in children.
  • Immunosuppressive drugs such as cyclosporine and azathioprine can delay some damage to dying muscle cells.
  • Drugs that may provide short-term relief from myotonia (muscle spasms and weakness) include mexiletine, phenytoin and baclofen, as they are known to block signals sent from the spinal cord to contract the muscles. Dantrolene interferes with the process of muscle contraction, and quinine is another option. 
  • The FDA granted accelerated approval of the drug Exondys 51 to treat individuals who have a confirmed mutation of the dystrophin gene amenable to exon 15 skipping. The accelerated approval means the drug can be administered to people who meet the rare disease criteria while the company works on additional trials to learn more about the effectiveness of the drug. (Drugs for myotonia may not be effective in myotonic MD but work well for myotonia congenita, a genetic neuromuscular disorder characterized by the slow relaxation of the muscles.) Respiratory infections may be treated with antibiotics.
• Physical therapy can help prevent malformation, improve movement and keep the muscles as flexible and strong as possible.
  • Passive stretching can increase joint flexibility and prevent contractures that restrict movement and cause loss of function.
  • Regular, moderate exercise can help people with MD maintain range of motion and muscle strength, prevent muscle atrophy and delay the development of contractures. Individuals with a weakened diaphragm can learn coughing and deep breathing exercises that are designed to keep the lungs fully expanded.
  • Postural correction is used to counter the muscle weakness, contractures and spinal irregularities that force individuals with MD into uncomfortable positions.
  • Support aids such as wheelchairs, splints and braces, other orthopedic appliances and overhead bed bars (trapezes) can help maintain mobility. Spinal supports can help delay scoliosis. Orthotic devices such as standing frames and swivel walkers can help people remain standing or walking.
  • Repeated low-frequency bursts of electrical stimulation to the thigh muscles may produce a slight increase in strength in some male children with Duchenne MD, though this therapy has not been proven to be effective.
• Occupational therapy may help some with progressive weakness and loss of mobility. Some individuals may need to learn new job skills or new ways to perform tasks, while other people may need to change careers altogether. Assistive technology may include modifications to home and workplace settings and the use of motorized wheelchairs, wheelchair accessories and adaptive utensils.
• Speech therapy may help individuals whose facial and throat muscles have weakened. They can learn to use special communication devices, such as a computer with a voice synthesizer.
• Dietary changes have not been shown to slow the progression of MD. Proper nutrition is essential, however, for overall health. Feeding techniques may help people with MD who have a swallowing disorder.
• Corrective surgery is often performed to ease complications from MD.
  • Tendon or muscle-release surgery is recommended when a contracture becomes severe enough to lock a joint or greatly impair movement.
  • Individuals with either Emery-Dreifuss or myotonic dystrophy may require a pacemaker at some point to treat cardiac problems.
  • Surgery to reduce the pain and postural imbalance caused by scoliosis may help some individuals. Scoliosis occurs when the muscles that support the spine begin to weaken and can no longer keep the spine straight.
  • People with myotonic dystrophy often develop cataracts, a clouding of the lens of the eye that blocks light, and may need cataract surgery.

While many neuromuscular disorders have no cure and are progressive, treatments can increase mobility, diminish symptoms and lengthen life. Patients can reduce pain, increase muscle control and reduce muscle degeneration by exercising regularly.

Depending on the type of muscular dystrophy (MD), many can live a long, full life. The leading cause of death for those with a MD diagnosis is heart disease, particularly cardiomyopathy. As MD is a progressive disease and there is no known cure, symptoms can be managed with a range of treatment options aimed at keeping people independent for as long as possible and to prevent complications that can arise from weakness, reduced mobility, and cardiac and respiratory difficulties. Treatment may involve a combination of approaches, including physical therapy, drug therapy and surgery. 

Other treatment types that can ease complications and improve quality of life are:

• Assisted ventilation
• Drug therapy 
• Physical therapy
• Occupational therapy
• Speech therapy
• Dietary changes/proper nutrition
• Corrective surgery