Muscular dystrophy


Muscular dystrophy is a group of muscle diseases that results in increasing weakening and breakdown of skeletal muscles over time. The disorders differ in which muscles are primarily affected, the degree of weakness, how fast they worsen, and when symptoms begin. Many people will eventually become unable to walk. Some types are also associated with problems in other organs.
The muscular dystrophy group contains thirty different genetic disorders that are usually classified into nine main categories or types. The most common type is Duchenne muscular dystrophy, which typically affects males beginning around the age of four. Other types include Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, limb-girdle muscular dystrophy, and myotonic dystrophy. They are due to mutations in genes that are involved in making muscle proteins. This can occur due to either inheriting the defect from one's parents or the mutation occurring during early development. Disorders may be X-linked recessive, autosomal recessive, or autosomal dominant. Diagnosis often involves blood tests and genetic testing.
There is no cure for muscular dystrophy. Physical therapy, braces, and corrective surgery may help with some symptoms. Assisted ventilation may be required in those with weakness of breathing muscles. Medications used include steroids to slow muscle degeneration, anticonvulsants to control seizures and some muscle activity, and immunosuppressants to delay damage to dying muscle cells. Outcomes depend on the specific type of disorder.
Duchenne muscular dystrophy, which represents about half of all cases of muscular dystrophy, affects about one in 5,000 males at birth. Muscular dystrophy was first described in the 1830s by Charles Bell. The word "dystrophy" is from the Greek dys, meaning "difficult" and troph meaning "nourish". Gene therapy, as a treatment, is in the early stages of study in humans.

Signs and symptoms

The signs and symptoms consistent with muscular dystrophy are:

Cause

These conditions are generally inherited, and the different muscular dystrophies follow various inheritance patterns. Muscular dystrophy can be inherited by individuals as an X-linked disorder, a recessive or dominant disorder. Furthermore, it can be a spontaneous mutation which means errors in the replication of DNA and spontaneous lesions. Spontaneous lesions are due to natural damage to DNA, where the most common are depurination and deamination.
Dystrophin protein is found in muscle fiber membrane; its helical nature allows it to act like a spring or shock absorber. Dystrophin links actin in the cytoskeleton and dystroglycans of the muscle cell plasma membrane, known as the sarcolemma. In addition to mechanical stabilization, dystrophin also regulates calcium levels.
The gene for dystrophin is located on the X chromosome. In males, the lone X chromosome has only one dystrophin gene. If there's a mutation in that gene, a male's muscles will lack dystrophin and slowly degenerate; mutations in the gene for dystrophin were identified as the cause of DMD by MDA researchers in 1986. A female almost always has two dystrophin genes, one on each X chromosome, and, even if one of these isn't working, the other gene suffices to keep dystrophin levels high enough to preserve muscle function in both the heart and skeletal muscles. Nevertheless, research has shown that a small minority of females having both a working and a non-working dystrophin gene can exhibit symptoms of DMD.
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.

Diagnosis

The diagnosis of muscular dystrophy is based on the results of muscle biopsy, increased creatine phosphokinase, electromyography, and genetic testing. 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.
Other tests that can be done are chest X-ray, echocardiogram, CT scan, and magnetic resonance image scan, which via a magnetic field can produce images whose detail helps diagnose muscular dystrophy. Quality of life can be measured using specific questionnaires.

Classification

Management

Currently, there is no cure for muscular dystrophy. In terms of management, physical therapy, occupational therapy, orthotic intervention, speech therapy, and respiratory therapy may be helpful. Low intensity corticosteroids such as prednisone, and deflazacort may help to maintain muscle tone. Orthoses and corrective orthopedic surgery may be needed to improve the quality of life in some cases. The cardiac problems that occur with EDMD and myotonic muscular dystrophy may require a pacemaker. The myotonia occurring in myotonic muscular dystrophy may be treated with medications such as quinine.
Occupational therapy assists the individual with MD to engage in activities of daily living 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; furthermore, it addresses psychosocial changes and cognitive decline which may accompany MD, and provides support and education about the disease to the family and individual.

Prognosis

Prognosis depends on the individual form of MD. In some cases, a person with a muscle disease will get progressively weaker to the extent that it shortens lifespan due to heart and breathing complications. However, some of the muscle diseases do not affect life expectancy at all, and ongoing research is attempting to find cures and treatments to slow muscle weakness.

History

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 the most common and severe form of the disease, which now carries his name—Duchenne MD.

Research

WHO International conducted trials on optimum steroid regimen for MD, in the UK in 2012. In terms of research within the United States, the primary federally funded organizations that focus on muscular dystrophy research, including gene therapy and regenerative medicine, are the National Institute of Neurological Disorders and Stroke, National Institute of Arthritis and Musculoskeletal and Skin Diseases, and National Institute of Child Health and Human Development.
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 telethon for portraying victims of the disease as deserving pity rather than respect.
On December 18, 2001, the MD CARE Act was signed into law in the USA; it 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.