Мышечные дистрофии: генетика, диагностика и классификация.

Genetic disorder
Over 30 different disorders are classified as muscular dystrophies. It links the muscle membrane to the thin muscular filaments within the cell. Dystrophin is an integral part of the muscular structure. An absence of dystrophin can cause impairments: healthy muscle tissue can be replaced by fibrous tissue and fat, causing an inability to generate force. Respiratory and cardiac complications can occur as well. These mutations are either inherited from parents or may occur spontaneously during early development. Many affected people will eventually become unable to walk

The majority of muscular dystrophies are inherited; the different muscular dystrophies follow various inheritance patterns (X linked, autosomal recessive or autosomal dominant). In a small percentage of patients, the disorder may have been caused by a de novo (spontaneous) mutation.

The diagnosis of muscular dystrophy is based on the results of muscle biopsy, increased creatine phosphokinase (CpK3), 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. An MRI can be used to assess the white matter of the nervous system and measure the merosin levels in young boys. An absence of merosin in young boys will result with neurological deficits and changes in the white matter.

Disorder nameOMIM GeneInheritance patternAge of onsetMuscles affected DescriptionBecker muscular dystrophyDMDXRChildhoodDistal limbs progressing to generalised weakness A less severe variant of Duchenne muscular dystrophy, affects predominantly boys. Congenital muscular dystrophy Multiple MultipleAD, ARAt birthGeneralised weakness Symptoms include general muscle weakness and possible joint deformities. Disease progresses slowly, and lifespan is shortened. 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. Several forms of the congenital muscular dystrophies are caused by defects in proteins 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. Typical lifespans range from 15 to 45. Distal muscular dystrophyDYSFAD, AR20–60 yearsDistal muscles in hands, forearms and lower legs Progress is slow and not life threatening. 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 limb–girdle muscular dystrophy. Facioscapulohumeral muscular dystrophyDUX4ADAdolescenceFace, shoulders, upper arms, progressing to other muscles Causes progressive weakness, initially in the muscles of the face, shoulders, and upper arms. Additional muscles are often affected. Affected individuals can become severely disabled, with 20% requiring a wheelchair by age 50. 30% of cases involve spontaneous mutations. Limb–girdle muscular dystrophy Multiple MultipleAD, ARAnyUpper arms and legs The person normally leads a normal life with some assistance. Rare cardiopulmonary complications can be life threatening. Myotonic muscular dystrophyDMPKCNBPADAdulthoodSkeletal muscles, heart, other muscle groups Presents with myotonia (delayed relaxation of muscles), as well as muscle wasting and weakness. Varies in severity and manifestations and affects many body systems in addition to skeletal muscles, including the heart, endocrine organs, and eyes. Oculopharyngeal muscular dystrophyPABPN1AD, rarely AR40–50 yearsEye muscles, face, throat, pelvis, shoulders

Currently, there is no cure for muscular dystrophy. In terms of management, physical therapy, occupational therapy, orthotic intervention (e. g., ankle foot orthosis), speech therapy, and respiratory therapy may be helpful. Low intensity corticosteroids such as prednisone, and deflazacort may help to 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 myotonia (delayed relaxation of a muscle after a strong contraction) occurring in myotonic muscular dystrophy may be treated with medications such as quinine. Low intensity, assisted exercises, dynamic exercise training, or assisted bicycle training of the arms and legs during a 24 week trial significantly delayed the functional loss of muscular dystrophy. It can be done in a safe and feasible manner, even with boys late in their ambulation stage. However, eccentric exercises, or intense exercises causing soreness should not be used as they can cause further damage. 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; 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 depends on the individual form of muscular dystrophy. Some dystrophies cause progressive weakness and loss of muscle function, which may result in severe physical disability and a life threatening deterioration of respiratory muscles or heart. Other dystrophies do not affect life expectancy and only cause relatively mild impairment. 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.

In 1966 in the US and Canada, Jerry Lewis and the Muscular Dystrophy Association (MDA) began the annual Labor Day telecast The Jerry Lewis Telethon, significant in raising awareness of muscular dystrophy in North America. Disability rights advocates, however, have criticized the telethon for portraying those living with the disease as deserving pity rather than respect. On December 18, 2001, the MD CARE Act was signed into law in the US; 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.