MUSCULAR DYSTROPHY - An Overview

Definition

By Mayo Clinic Staff

Muscular dystrophy is a group of genetic diseases in which muscle fibers are unusually susceptible to damage. These damaged muscles become progressively weaker. Most people who have muscular dystrophy will eventually need to use a wheelchair.

There are many different kinds of muscular dystrophy. Symptoms of the most common variety begin in childhood, primarily in boys. Other types of muscular dystrophy don't surface until adulthood.

People who have muscular dystrophy may have trouble breathing or swallowing. Their limbs may also draw inward and become fixed in that position — a problem called contracture. Some varieties of the disease can also affect the heart and other organs.

While there is no cure for muscular dystrophy, medications and therapy can slow the course of the disease.

Symptoms

By Mayo Clinic Staff

Progressive muscle weakness is the main feature of muscular dystrophy. Each separate form of muscular dystrophy varies a bit in terms of the age at which the signs and symptoms usually begin and the sequence in which different muscle groups are affected.

Duchenne muscular dystrophy

About half of all muscular dystrophy cases are the Duchenne variety, which most commonly occurs in boys. Signs and symptoms typically first surface when the child begins to walk and may include:

• Frequent falls
• Difficulty getting up from a lying or sitting position
• Trouble running and jumping
• Waddling gait
• Large calf muscles
• Learning disabilities

Becker muscular dystrophy

This variety has signs and symptoms similar to Duchenne muscular dystrophy, but they typically are milder and progress more slowly. Symptom onset is generally in the teens but may not occur until the mid-20s or even later.

Other types of muscular dystrophy

Certain other types of muscular dystrophy are defined by a specific feature or the location of the body where symptoms first begin. Examples include:

• Myotonic. Also known as Steinert's disease, this form of muscular dystrophy also features an inability to relax muscles at will. It most often begins in early adulthood. Muscles of the face are usually the first to be affected.
• Limb-girdle. The hip and shoulder muscles are usually the first affected in this type of muscular dystrophy. In some cases, it becomes difficult to lift the front part of the foot, so frequent tripping may occur. Signs and symptoms may begin from early childhood to adulthood.
• Congenital. This category of muscular dystrophy is apparent at birth or becomes evident before age 2. Some forms progress slowly and cause only mild disability, while others progress rapidly and cause severe impairment.
• Fascioscapulohumeral (FSHD). One of the most striking signs of this variety of muscular dystrophy is that the shoulder blades might stick out like wings when the person raises his or her arms. Onset usually occurs in teens or young adults.
• Oculopharyngeal. The first sign of this type of muscular dystrophy is usually drooping of the eyelids. Weakness of the muscles of the eye, face and throat often results in swallowing difficulties. Signs and symptoms first appear in adulthood, usually in a person's 40s or 50s.

When to see a doctor

Seek medical advice if you notice signs of muscle weakness — such as increased clumsiness and falling — in yourself or your child.

Causes

By Mayo Clinic Staff

Hundreds of genes are involved in making proteins that protect muscle fibers from damage. Muscular dystrophy occurs when one of these genes is defective. Each form of muscular dystrophy is caused by a genetic mutation that's particular to that type of the disease. Many of these mutations are inherited, but some occur spontaneously in the mother's egg or the developing embryo.

Risk factors

By Mayo Clinic Staff

Muscular dystrophy occurs in both sexes and in all ages and races, but the most common variety usually occurs in young boys. People who have a family history of muscular dystrophy are at higher risk of developing the disease or passing it on to their children.

Complications

By Mayo Clinic Staff

Some types of muscular dystrophy shorten the person's lifespan, often by affecting the muscles associated with breathing. Even with improved mechanical breathing assistance, people who have Duchenne muscular dystrophy — the most common type of muscular dystrophy — usually die of respiratory failure before they reach age 40.

Many types of muscular dystrophy can also reduce the efficiency of the heart muscle. If the muscles involved with swallowing are affected, nutritional problems may develop.

As muscle weakness progresses, mobility becomes a problem. Many people who have muscular dystrophy will eventually need to use a wheelchair. However, the prolonged immobility of joints associated with wheelchair use can worsen contractures, in which the limbs draw inward and become fixed in that position.

Contractures may also play a part in the development of scoliosis, a sideways curvature of the spine that further reduces lung efficiency in people who have muscular dystrophy.

Preparing for your appointment

By Mayo Clinic Staff

ou'll probably first bring your concerns to the attention of your family doctor, but you may be referred to a doctor who specializes in the diagnosis and treatment of muscular dystrophy.

What you can do

If you are worried that your child might have muscular dystrophy, you might want to bring photos or video recordings that illustrate your particular concerns. Bring along a relative or friend to help listen to the doctor's information.

Questions to ask the doctor include:

• What is likely causing these signs and symptoms?
• Are there any other possible causes for these symptoms?
• What kinds of tests are needed?
• What are the possible complications of this condition?
• How is this condition treated?
• What is the long-term outlook?
• How can I find other families who are coping with the same diagnosis?

What to expect from your doctor

The doctor is likely to ask you a number of questions. Being ready to answer them may reserve time to go over any points you want to talk about in depth. The doctor may ask:

• What symptoms have you noticed?
• When did they start? Are they getting worse?
• Has anyone in your immediate family had muscular dystrophy?
• Do you plan on having more children?

Tests and diagnosis

By Mayo Clinic Staff

In addition to a medical history review and physical examination, your doctor may suggest some of the following tests:

• Enzyme tests. Damaged muscles release enzymes, such as creatine kinase (CK), into your blood. In the absence of traumatic injuries, high blood levels of CK suggest a muscle disease — such as muscular dystrophy.
• Electromyography. This test involves inserting an electrode needle through your skin and into the muscle to be tested. Electrical activity is measured as you relax and as you gently tighten the muscle. Changes in the pattern of electrical activity can confirm a muscle disease.
• Muscle biopsy. A small piece of muscle can be removed through a small incision or with a hollow needle. The analysis of the sample can distinguish muscular dystrophies from other muscle diseases.
• Genetic testing. Blood samples can be examined for mutations in some of the genes that cause different types of muscular dystrophy.

Treatments and drugs

By Mayo Clinic Staff

There's currently no cure for any form of muscular dystrophy. Research into gene therapy may eventually provide treatment to stop the progression of some types of muscular dystrophy. Current treatment is designed to help prevent or reduce deformities in the joints and the spine and to allow people with muscular dystrophy to remain mobile as long as possible.

Medications

Corticosteroids, such as prednisone, may help improve muscle strength and delay the progression of certain types of muscular dystrophy. But prolonged use of these types of drugs can weaken bones and increase fracture risk.

Therapy

Several different types of therapy and assistive devices can improve quality and sometimes length of life in people who have muscular dystrophy. Examples include:

• Range-of-motion exercises. Muscular dystrophy can restrict the flexibility and mobility of joints. Limbs often draw inward and become fixed in that position. One goal of physical therapy is to provide regular range-of-motion exercises to keep joints as flexible as possible.
• Mobility aids. Braces can provide support for weakened muscles and help keep muscles and tendons stretched and flexible, slowing the progression of contractures. Other devices — such as canes, walkers and wheelchairs — can helfp maintain mobility and independence.
• Breathing assistance. As respiratory muscles weaken, a sleep apnea device may help improve oxygen delivery during the night. Some people with severe muscular dystrophy may need to rely on a ventilator — a machine that forces air in and out of their lungs.

Surgical and other procedures

Surgical remedies are an option for several of the problems common to muscular dystrophy, such as:

• Contractures. Tendon surgery can loosen joints drawn inward by contractures.
• Scoliosis. Surgery may also be needed to correct a sideways curvature of the spine that can make breathing more difficult.
• Heart problems. Some people who have heart problems related to muscular dystrophy may be helped by the insertion of a pacemaker, which prompts the heart to beat more regularly.

Lifestyle and home remedies

By Mayo Clinic Staff

Because respiratory infections may become a problem in later stages of muscular dystrophy, it's important to be vaccinated for pneumonia and to keep up to date with influenza shots.

Coping and support

By Mayo Clinic Staff

For family members of people with muscular dystrophy, coping with the illness involves major commitment of physical, emotional and financial resources. The disease presents challenges in the classroom, in the home and in all aspects of life.

In dealing with muscular dystrophy, support groups can be a valuable part of a wider network that includes health care professionals, family, friends and community organizations, including places of worship.

Support groups bring together people, family and friends who are all coping with the same kind of physical or mental health challenge. Support groups provide a setting in which people can share their common problems and provide ongoing support to one another.

Ask your doctor about self-help groups that may exist in your community. Your local health department, public library, telephone book and the Internet also may be good sources to locate a support group in your area.

Source: http://www.mayoclinic.org/

MUSCULAR DYSTROPHY - From Wikipedia, the free encyclopedia

From Wikipedia, the free encyclopedia

Muscular Dystrophy
Classification and external resources
In affected muscle (right) the tissue becomes disorganized and the concentration of dystrophin (green) is greatly reduced, compared to normal muscle (left).
ICD-10	G71.0
ICD-9	359.0-359.1
MedlinePlus	001190
eMedicine	orthoped/418
MeSH	D009136

Muscular dystrophy (MD) is a group of muscle diseases that weaken the musculoskeletal system and hamper locomotion.^[1][2] Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue.^[3]

In the 1860s, descriptions of boys who grew progressively weaker, lost the ability to walk, and died at an early age became more prominent in medical journals. In the following decade, French neurologist Guillaume Duchenne gave a comprehensive account of thirteen boys with the most common and severe form of the disease, which now carries his name—Duchenne muscular dystrophy.

It soon became evident that the disease had more than one form. The other major forms are Becker, limb-girdle,congenital, facioscapulohumeral, myotonic, oculopharyngeal, distal, and Emery-Dreifuss muscular dystrophy.^[4] Duchenne and Becker muscular dystrophies, being caused by a mutation of a gene located on the X chromosome, predominantly affect males, although females can sometimes have severe symptoms as well. Most types of MD are multi-system disorders with manifestations in body systems including the heart, gastrointestinal system, nervous system, endocrine glands, eyes and brain.^[4]

Apart from the nine major types of muscular dystrophy listed above, several MD-like conditions have also been identified. Normal intellectual, muscular, behavioral, bowel and sexual function is noticed in individuals with other forms of MD and MD-like conditions.^[5][6] MD-affected individuals with susceptible intellectual impairment are diagnosed through molecular characteristics but not through problems associated with disability.^[7] However, a third of patients who are severely affected with DMD may have cognitive impairment, behavioral, vision and speech problems.^[8][9]

Signs and symptoms

• Progressive muscular wasting
• Poor balance
• Drooping eyelids
• Atrophy
• Scoliosis (curvature of the spine and the back)
• Inability to walk
• Frequent falls
• Waddling gait
• Calf deformation
• Limited range of movement
• Respiratory difficulty
• Joint contractures
• Cardiomyopathy
• Arrhythmias
• Muscle spasms
• Gowers' sign^[10]

Cause

These conditions are generally inherited, and the different muscular dystrophies follow various inheritance patterns. However, mutations of the dystrophin gene and nutritional defects (with no genetics history) at the prenatal stage are also possible in about 33% of people affected by DMD.^[11] The main cause of the Duchenne and Becker types of muscular dystrophy is the muscle tissue's cytoskeletal impairment to properly create the functional protein dystrophin and dystrophin-associated protein complex.

Dystrophin protein is found in muscle fibre membrane; its helical nature allows it to act like a spring or shock absorber. Dystrophin links actin (cytoskeleton) and dystroglycans of the muscle cell plasma membrane, known as the sarcolemma (extracellular). In addition to mechanical stabilization, dystrophin also regulates calcium levels.^{[citation needed]}. Recent studies on the interaction of proteins with missense mutations and its neighbors showed high degree of rigidity associated with central hub proteins involved in protein binding and flexible subnetworks having molecular functions involved with calcium. ^[12]

Diagnosis

Histopathology of gastrocnemius muscle from patient who died of pseudohypertrophic muscular dystrophy, Duchenne type. Cross section of muscle shows extensive replacement of muscle fibers by adipose cells.

The diagnosis of muscular dystrophy is based on the results of muscle biopsy, increased creatine phosphokinase (CpK3), electromyography, electrocardiography and DNA analysis.

A physical examination and the patient's medical history will help the doctor determine the type of muscular dystrophy. Specific muscle groups are affected by different types of muscular dystrophy.

Often, there is a loss of muscle mass (wasting), which may be hard to see because some types of muscular dystrophy cause a buildup of fat and connective tissue that makes the muscle appear larger. This is called pseudohypertrophy.

Management

There is no known cure for muscular dystrophy, although significant headway is being made with antisense oligonucleotides.^[13] Physical therapy, occupational therapy, orthotic intervention (e.g., ankle-foot orthosis), speech therapy and orthopedic instruments (e.g., wheelchairs, standing frames and powered mobile arm supports) may be helpful. Inactivity (such as bed rest, sitting for long periods) and bodybuilding efforts to increase myofibrillar hypertrophy can worsen the disease.

There is no specific treatment for any of the forms of muscular dystrophy. Physiotherapy, aerobic exercise, low intensity anabolic steroids, prednisone supplements may help to prevent contractures and maintain muscle tone. Orthoses (orthopedic appliances used for support) and corrective orthopedic surgery may be needed to improve the quality of life in some cases. The cardiac problems that occur with Emery-Dreifuss muscular dystrophy and myotonic muscular dystrophy may require a pacemaker. The myotonia (delayed relaxation of a muscle after a strong contraction) occurring in myotonic muscular dystrophy may be treated with medications such as quinine, phenytoin, or mexiletine, but no actual long term treatment has been found.

Occupational therapy assists the individual with MD to engage in activities of daily living (such as self-feeding and self-care activities) and leisure activities at the most independent level possible. This may be achieved with use of adaptive equipment or the use of energy conservation techniques. Occupational therapy may implement changes to a person's environment, both at home or work, to increase the individual's function and accessibility. Occupational therapists also address psychosocial changes and cognitive decline which may accompany MD, as well as provide support and education about the disease to the family and individual.^[14]

High dietary intake of lean meat, seafood, pulses, olive oil, antioxidants such as leafy vegetables and bell peppers, and fruits like blueberry and cherry is advised. Decreased intake of refined food, trans fats, and caffeinated and alcoholic beverages is also advised, as is a check for any food allergies.^[15]

After diagnosis, medical care may include services in neurology, nutrition, gastroenterology, respiratory care, cardiac care, orthopedics, psychosocial, rehabilitation, and oral care.

Prognosis

The prognosis for people with muscular dystrophy varies according to the type and progression of the disorder. Some cases may be mild and progress very slowly over a normal lifespan, while others produce severe muscle weakness, functional disability, and loss of the ability to walk. Some children with muscular dystrophy die in infancy while others live into adulthood with only moderate disability. The muscles affected vary, but can be around the pelvis, shoulder, face or elsewhere. Muscular dystrophy can affect adults, but the more severe forms tend to occur in early childhood.

Types

Type	OMIM	Gene	Description
Becker muscular dystrophy	300376	DMD	Becker muscular dystrophy (BMD) is a less severe variant of Duchenne muscular dystrophy and is caused by the production of a truncated, but partially functional form of dystrophin.[4] Survival is usually into old age.[16] Affects only boys (with extremely rare exceptions)
Congenital muscular dystrophy	Multiple	Multiple	Age at onset: birth; symptoms include general muscle weakness and possible joint deformities; disease progresses slowly; shortened life span.[17] Congenital muscular dystrophy includes several disorders with a range of symptoms. Muscle degeneration may be mild or severe. Problems may be restricted to skeletal muscle, or muscle degeneration may be paired with effects on the brain and other organ systems. A number of the forms of the congenital muscular dystrophies are caused by defects in proteins that are thought to have some relationship to the dystrophin-glycoprotein complex and to the connections between muscle cells and their surrounding cellular structure. Some forms of congenital muscular dystrophy show severe brain malformations, such as lissencephaly and hydrocephalus.[4]
Duchenne muscular dystrophy	310200	DMD	Duchenne muscular dystrophy (DMD) is the most common childhood form of muscular dystrophy; it generally affects only boys (with extremely rare exceptions), becoming clinically evident when a child begins walking. By age 10, the child may need braces for walking and by age 12, most patients are unable to walk.[18] Life span ranges from 15 to 51.[18] In the early 1990s, researchers identified the gene for the protein dystrophin which, when absent, causes DMD. The amount of dystrophin correlates with the severity of the disease (i.e., the less dystrophin present, the more severe the phenotype). Since the gene is on the X chromosome, this disorder affects primarily males, and females who are carriers have milder symptoms. Sporadic mutations in this gene occur frequently, accounting for a third of cases. The remaining two-thirds of cases are inherited in a recessive pattern. Dystrophin is part of a complex structure involving several other protein components. The "dystrophin-glycoprotein complex" helps anchor the structural skeleton (cytoskeleton) within the muscle cells, through the outer membrane (sarcolemma) of each cell, to the tissue framework (extracellular matrix) that surrounds each cell. Due to defects in this assembly, contraction of the muscle leads to disruption of the outer membrane of the muscle cells and eventual weakening and wasting of the muscle.[4]
Distal muscular dystrophy	254130	DYSF	Distal muscular dystrophies' age at onset: 20 to 60 years; symptoms include weakness and wasting of muscles of the hands, forearms, and lower legs; progress is slow and not life-threatening.[16] Miyoshi myopathy, one of the distal muscular dystrophies, causes initial weakness in the calf muscles, and is caused by defects in the same gene responsible for one form of LGMD (Limb Girdle Muscular Dystrophy).[4]
Emery-Dreifuss muscular dystrophy	310300,181350	EMD,LMNA	Emery-Dreifuss Muscular Dystrophy patients normally present in childhood and the early teenage years with contractures. Clinical signs include muscle weakness and wasting, starting in the distal limb muscles and progressing to involve the limb-girdle muscles. Most patients also suffer from cardiac conduction defects and arrhythmias which, if left untreated, increase the risk of stroke and sudden death. There are three subtypes of Emery-Dreifuss Muscular Dystrophy, distinguishable by their pattern of inheritance: X-Linked, autosomal dominant and autosomal recessive. The X-linked form is the most common. Each type varies in prevalence and symptoms. The disease is caused by mutations in the LMNA gene, or more commonly, the EMD gene. Both genes encode for protein componenets of the nuclear envelope. However, how these mutations cause the pathogenesis is not well understood.[19]
Facioscapulohumeral muscular dystrophy	158900	DUX4	Facioscapulohumeral muscular dystrophy (FSHD) initially affects the muscles of the face, shoulders, and upper arms with progressive weakness. Symptoms usually develop in the teenage years. Some affected individuals become severely disabled. The pattern of inheritance is autosomal dominant, but there are a significant number of spontaneous mutations. Seminal research published in August 2010 documents that two defects are needed for FSHD, which for the first time provides a unifying theory for the underlying genetics of FSHD. The first is the deletion of D4Z4 repeats and the second is a "toxic gain of function" of the DUX4 gene.[4][20][21] Facioscapulohumeral muscular dystrophy (FSHD) occurs both in males and females.
Limb-girdle muscular dystrophy	Multiple	Multiple	Limb-girdle muscular dystrophy is also called LGMD. Affects both boys and girls. LGMDs all show a similar distribution of muscle weakness, affecting both upper arms and legs. Many forms of LGMD have been identified, showing different patterns of inheritance (autosomal recessive vs. autosomal dominant). In an autosomal recessive pattern of inheritance, an individual receives two copies of the defective gene, one from each parent. The recessive LGMDs are more frequent than the dominant forms, and usually have childhood or teenage onset. The dominant LGMDs usually show adult onset. Some of the recessive forms have been associated with defects in proteins that make up the dystrophin-glycoprotein complex.[4] Though a person normally leads a normal life with some assistance, in some extreme cases, death from LGMD occurs due to cardiopulmonary complications.[22]
Myotonic muscular dystrophy	160900,602668	DMPK,ZNF9	Myotonic muscular dystrophy is an autosomal dominant condition that presents with myotonia (delayed relaxation of muscles) as well as muscle wasting and weakness.[23] Myotonic dystrophy varies in severity and manifestations and affects many body systems in addition to skeletal muscles, including the heart, endocrine organs, eyes, and gastrointestinal tract. Myotonic muscular dystrophy type 1 (DM1), also known as Steinert disease, is the most common adult form of muscular dystrophy. It results from the expansion of a short (CTG) repeat in the DNA sequence of the DMPK (myotonic dystrophy protein kinase) gene. Myotonic muscular dystrophy type 2 (DM2) is much rarer and is a result of the expansion of the CCTG repeat in the ZNF9 (zinc finger protein 9) gene. While the exact mechanisms of action are not known, these molecular changes may interfere with the production of important muscle proteins.[4]
Oculopharyngeal muscular dystrophy	164300	PABPN1	Oculopharyngeal MD's age at onset: 40 to 70 years; symptoms affect muscles of eyelids, face, and throat followed by pelvic and shoulder muscle weakness, has been attributed to a short repeat expansion in the genome which regulates the translation of some genes into functional proteins.[4]

Research funding

Within the United States, the three primary federally funded organizations that focus on muscular dystrophy research, including gene therapy, regenerative medicine) etc., include the National Institute of Neurological Disorders and Stroke (NINDS), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and National Institute of Child Health and Human Development (NICHD).^[4]

In 1966, the Muscular Dystrophy Association began its annual Jerry Lewis MDA Telethon, which has probably done more to raise awareness of muscular dystrophy than any other event or initiative. Disability rights advocates, however, have criticized the Jerry Lewis Telethon for portraying victims of the disease as deserving pity rather than respect.^[24]

On December 18, 2001, the MD CARE Act was signed into law and amends the Public Health Service Act to provide research for the various muscular dystrophies. This law also established the Muscular Dystrophy Coordinating Committee to help focus research efforts through a coherent research strategy.^[25][26]

Source: http://en.wikipedia.org/