| Muscular Dystrophy | |
|---|---|
| Classification and external resources | |
| ICD-10 | G71.0 |
| ICD-9 | 359.0-359.1 |
| MedlinePlus | 001190 |
| eMedicine | orthoped/418 |
| MeSH | D009136 |
Muscular dystrophy (abbreviated MD) refers to a group of hereditary muscle diseases that weaken the muscles that move the human body.[1][2] Muscular dystrophies are characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue.[3] Nine diseases including Duchenne, Becker, limb girdle, congenital, facioscapulohumeral, myotonic, oculopharyngeal, distal, and Emery-Dreifuss are always classified as muscular dystrophy[4] but there are more than 100 diseases in total with similarities to muscular dystrophy. Most types of MD are multi-system disorders with manifestations in body systems including the heart, gastrointestinal and nervous systems, endocrine glands, skin, eyes and other organs, namely the brain. The condition may also lead to mood swings and learning difficulties.[4]
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 13 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, and that these diseases affected males of all ages.
Main symptoms include:
Few or none of these symptoms may be present before diagnosis. Some types of muscular dystrophy can affect the heart, causing cardiomyopathy or arrhythmias.
These conditions are inherited, and the different muscular dystrophies follow various inheritance patterns.
Chronic potassium deficiency (hypokalemia) may trigger or cause a progression in muscular dystrophy symptoms.
The diagnosis of muscular dystrophy is based on the results of a muscle biopsy and increased creatine phosphokinase (CpK3). In some cases, a DNA blood test may be all that is needed.
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 build up of fat and connective tissue that makes the muscle appear larger. This is called pseudohypertrophy.
There is no known cure for muscular dystrophy. Inactivity (such as bed rest and even sitting for long periods) can worsen the disease. Physical therapy, occupational therapy, orthotic intervention, speech therapy and orthopedic instruments (e.g., wheelchairs, standing frames) may be helpful.
There is no specific treatment for any of the forms of muscular dystrophy. Physical therapy 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 in engaging in his/her activities of daily living (self-feeding, self-care activities, etc) 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.[5]
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.
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.[6]
Age at onset: birth; symptoms include general muscle weakness and possible joint deformities; disease progresses slowly; shortened life span.
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 (DMD) is the most common childhood form of muscular dystrophy, becoming clinically evident when a child begins walking. Patients typically require a wheelchair by age 10 to 12 and die in their late teens to early 30s,[7] though some people with Duchenne muscular dystrophy are now living to age 40 and beyond. In the early 1990s, researchers identified the gene for the protein dystrophin which, when absent, causes DMD. 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 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.[6]
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 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 the pathogenesis of these mutations is not well understood.[8]
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 the underlying genetic defect is poorly understood. Most cases are associated with a deletion near the end of chromosome 4.[4]
Limb-girdle muscular dystrophy is also called LGMD. 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] Death from LGMD is usually due to cardiopulmonary complications.
Myotonic MD's age at onset: 20 to 40 years Myotonic muscular dystrophy is the most common adult form of muscular dystrophy. It is marked by myotonia as well as muscle wasting and weakness. 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 dystrophy follows an autosomal dominant pattern of inheritance. Myotonic dystrophy results from the expansion of a short repeat in the DNA sequence (CTG in one gene or CCTG in another gene). In other words, the gene defect is an abnormally long repetition of a three- or four-letter "word" in the genome. While the exact mechanism of action is not known, this molecular change may interfere with the production of important muscle proteins.[4]
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]
Spinal muscular atrophy (SMA) is a neuromuscular disease characterized by degeneration of motor neurons, resulting in progressive muscular atrophy (wasting away) and weakness. The clinical spectrum of SMA ranges from early infant death to normal adult life with only mild weakness. These patients often require comprehensive medical care involving multiple disciplines, including pediatric pulmonology, pediatric neurology, pediatric orthopedic surgery, pediatric critical care, and physical medicine and rehabilitation; and physical therapy, occupational therapy, respiratory therapy, and clinical nutrition. Genetic counseling is also helpful for the parents and family members.
The term "juvenile spinal muscular atrophy" refers to Kugelberg-Welander syndrome.
The Brown-Vialetto-Van Laere syndrome (BVVL), sometimes better known as Brown's Syndrome, is an exceptionally rare neurological disorder of unknown cause, characterized primarily by deafness and paralysis of the muscles of the face, neck, shoulders and limbs. The neurological manifestations develop insidiously: they usually begin with sensorineural deafness, progress inexorably to paralysis, and often culminate in respiratory failure. The syndrome affects children, adolescents, and younger adults; the age at onset of symptoms in the reported cases has ranged from infancy to the third decade of life. The prognosis is poor — most patients diagnosed with the syndrome die within 10 years. There is no cure.
To date, there is no test of confirmation for BVVL, although researchers are currently searching to isolate the responsible gene and are enlisting BVVL and Fazio-Londe patients and their families to contribute DNA to the BVVL BioBank (http://www.bvvl.org). It has been proposed that Fazio-Londe disease and Brown-Vialetto-Van-Laere syndrome are a phenotypically associated condition.
The syndrome was first described by Charles Brown in 1894; further accounts by Vialetto and Van Laere followed in 1936 and 1966, respectively. There are fewer than 60 cases reported in the medical literature over the 100 odd years since its first description.
Official web site: http://www.bvvlinternational.org
It produces rapidly progressive weakness of tongue, face and pharyngeal muscles in a clinical pattern similar to myasthenia bulbar palsy. Neuromuscular transmission may be abnormal in these muscles because of rapid denervation and immature reinervation, and strength may improve with administration of cholinesterase inhibitors. Paralysis occurs secondary to degeneration of the motor neurons of the brain stem. It causes progressive bulbar paralysis due to involvement of motor neurons of the cranial nerve nuclei. The most frequent symptoms at onset of progressive bulbar paralysis of childhood has been a unilateral facial paralysis. It is followed in frequency by dysarthria due to facial weakness or by dysphagia. Palatal weakness and palpebral ptosis also have been reported in few patients. Both sexes can be affected.
It has been proposed that Fazio-Londe disease and Brown-Vialetto-Van-Laere syndrome are a phenotypically associated condition.[3]
Within the United States, the three primary federally funded organizations that focus on muscular dystrophy 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 arguably done more to raise awareness of muscular dystrophy than any other event or initiative.
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.[9][10]
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