Muscular dystrophy

Jump to navigation Jump to search
Muscular Dystrophy
ICD-10 G71.0
ICD-9 359.0-359.1
MedlinePlus 001190
MeSH D009136

WikiDoc Resources for Muscular dystrophy

Articles

Most recent articles on Muscular dystrophy

Most cited articles on Muscular dystrophy

Review articles on Muscular dystrophy

Articles on Muscular dystrophy in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Muscular dystrophy

Images of Muscular dystrophy

Photos of Muscular dystrophy

Podcasts & MP3s on Muscular dystrophy

Videos on Muscular dystrophy

Evidence Based Medicine

Cochrane Collaboration on Muscular dystrophy

Bandolier on Muscular dystrophy

TRIP on Muscular dystrophy

Clinical Trials

Ongoing Trials on Muscular dystrophy at Clinical Trials.gov

Trial results on Muscular dystrophy

Clinical Trials on Muscular dystrophy at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Muscular dystrophy

NICE Guidance on Muscular dystrophy

NHS PRODIGY Guidance

FDA on Muscular dystrophy

CDC on Muscular dystrophy

Books

Books on Muscular dystrophy

News

Muscular dystrophy in the news

Be alerted to news on Muscular dystrophy

News trends on Muscular dystrophy

Commentary

Blogs on Muscular dystrophy

Definitions

Definitions of Muscular dystrophy

Patient Resources / Community

Patient resources on Muscular dystrophy

Discussion groups on Muscular dystrophy

Patient Handouts on Muscular dystrophy

Directions to Hospitals Treating Muscular dystrophy

Risk calculators and risk factors for Muscular dystrophy

Healthcare Provider Resources

Symptoms of Muscular dystrophy

Causes & Risk Factors for Muscular dystrophy

Diagnostic studies for Muscular dystrophy

Treatment of Muscular dystrophy

Continuing Medical Education (CME)

CME Programs on Muscular dystrophy

International

Muscular dystrophy en Espanol

Muscular dystrophy en Francais

Business

Muscular dystrophy in the Marketplace

Patents on Muscular dystrophy

Experimental / Informatics

List of terms related to Muscular dystrophy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [2] Associate Editor(s)-in-Chief: Kalsang Dolma, M.B.B.S.[3]

Overview

Muscular dystrophy refers to a group of genetic, hereditary muscle diseases that cause progressive muscle weakness.[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.[4]

Historical Perspective

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.[4]

Classification Scheme

Type OMIM Gene Description
Becker's muscular dystrophy 300376 DMD
  • Becker muscular dystrophy (BMD) is a less severe variant of Duchenne muscular dystrophy.
  • It is caused by the production of a truncated, but partially functional form of dystrophin.[4] Survival is usually into old age.[5]
  • 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.[6]
  • 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 confined to a wheelchair.[7]
  • Patients usually die around age 25, but this depends from person to person.[7]
  • 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.[5]
  • 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 the pathogenesis of these mutations is not well understood.[8]
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][9]

[10]

  • 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.[11]
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.[12] * 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]

Pathophysiology

Genetic

These conditions are inherited, and the different muscular dystrophies follow various inheritance patterns

The best-known type, Duchenne muscular dystrophy (DMD), is inherited in an X-linked recessive pattern, meaning that the mutated gene that causes the disorder is located on the X chromosome, one of the two sex chromosomes, and is thus considered sex-linked. In males (who have only one X chromosome) one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes) a mutation must generally be present in both copies of the gene to cause the disorder (relatively rare exceptions, manifesting carriers, do occur due to dosage compensation/X-inactivation). Males are therefore affected by X-linked recessive disorders much more often than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons. In about two thirds of DMD cases, an affected male inherits the mutation from a mother who carries one altered copy of the DMD gene. The other one third of cases probably result from new mutations in the gene. Females who carry one copy of a DMD mutation may have some signs and symptoms related to the condition (such as muscle weakness and cramping), but these are typically milder than the signs and symptoms seen in affected males. Duchenne muscular dystrophy and Becker's muscular dystrophy are caused by mutations of the gene for the dystrophin protein and lead to an overabundance of the enzyme creatine kinase.[13][14] The dystrophin gene is the second largest gene in mammals.[15]

Symptoms

Principal symptoms include:

  • Progressive Muscular Wasting (weakness)
  • Poor Balance
  • Frequent Falls
  • Walking Difficulty
  • Waddling Gait
  • Calf Pain
  • Limited Range of Movement
  • Muscle Contractures
  • Respiratory Difficulty
  • Drooping Eyelids (ptosis)
  • Gonadal Atrophy
  • Scoliosis (curvature of the spine)
  • Inability to walk

Some types of Muscular Dystrophy can affect the heart, causing cardiomyopathy or arrhythmias.

Diagnosis

The diagnosis of muscular dystrophy is based on the results of a muscle biopsy. 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.

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.

Some types of Muscular Dystrophy can affect the heart, causing cardiomyopathy or arrhythmias.

Treatment

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 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 (a condition when an individual with a muscular dystrophy grows and the muscles don't move with the bones and can easily be slowed down and/or make the individual's body straighter by daily physical therapy), 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.

Research Projects

A grid computing-based research project called "Help Cure Muscular Dystrophy" was launched on December 19, 2006 by Décrypthon (a collaboration between French Muscular Dystrophy Association, French National Center for Scientific Research and IBM).

The Jain Foundation is involved in research into Miyoshi myopathy, a form of distal muscular dystrophy and LGMD2B, a limb-girdle muscular dystrophy.[16]

MY0-029

MYO-029 is an experimental myostatin inhibiting drug developed by Wyeth Pharmaceuticals for the treatment of muscular dystrophy. Myostatin is a protein that inhibits the growth of muscle tissue, MYO-029 is a recombinant human antibody designed to bind and inhibit the activity of myostatin. A 2005/2006 trial was completed by Wyeth in Collegeville, PA. As of April 2007, the results of the study have not yet been made public, but it is one of the few known drugs in development for the treatment for muscular dystrophy.

National research and support in the United States

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.[17][18]

Types of Muscular Dystrophy

Becker's muscular dystrophy (BMD)

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 middle age. [5]

Congenital muscular dystrophy

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 pair 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)

Duchenne muscular dystrophy (DMD) is the most common childhood form of muscular dystrophy. DMD usually becomes clinically evident when a child begins walking. Patients typically require a wheelchair by age 10 to 12 and die in their late teens or early 20s. In the early 1990s, researchers identified the gene for the protein dystrophin which, when absent, causes DMD. The dystrophin gene is the largest known gene in humans. Since the gene is on the X-chromosome, this disorder affects primarily males. Females who are carriers have milder symptoms. Sporadic mutations in this gene occur frequently, accounting for a third of cases. The remianing two-thirds of cases are inherited in a recessive pattern. age at onset: two to six years; symptoms include general muscle weakness and wasting; affects pelvis, upper arms, and upper legs; eventually involves all voluntary muscles; survival beyond 20 years is rare.[4]

Dystrophin is part of a complex structure involving several other protein components. The "dystrophin-glycoprotein complex" helps anchor the structural skeleton within the muscle cells, through the outer membrane of each cell, to the tissue framework 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

Distal muscular dystrophies' age at onset: 40 to 60 years; symptoms include weakness and wasting of muscles of the hands, forearms, and lower legs; progress is slow and not life-threatening.

Facioscapulohumeral muscular dystrophy (FSHD)

FSHD initially affects 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 (LGMD)

LGMD's 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 muscular dystrophy

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 genetic code. While the exact mechanism of action is not known, this molecular change may interfere with the production of important muscle proteins.[4]

Oculopharyngeal muscular dystrophy

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 a gene which regulates the translation of the genetic code into functional proteins.[4]

References

  1. Harrison's Principle's of Internal Medicine. 2005. p. 2527. doi:10.1036/0071402357. Unknown parameter |coauthors= ignored (help)
  2. Muscular Dystrophy Campaign Retrieved 9 April 2007.
  3. Emery AE (2002). "The muscular dystrophies". Lancet. 359 (9307): 687–695. PMID 11879882.
  4. 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 4.11 4.12 4.13 4.14 4.15 4.16 4.17 4.18 4.19 May 2006 report to Congress on Implementation of the MD CARE Act, as submitted by Department of Health and Human Service's National Institutes of Health
  5. 5.0 5.1 5.2 [1]: MD USA Website (accessed 03SEP2007)
  6. "Congenital Muscular Dystrophy (CMD)". MDA. Retrieved 27 April 2012.
  7. 7.0 7.1 http://www.nlm.nih.gov/medlineplus/ency/article/000705.htm
  8. Emedicine re EDMD Retrieved 30 July 2007.
  9. Kolata, Gina (19 August 2010). "Reanimated 'Junk' DNA Is Found to Cause Disease". New York Times. Retrieved 29 August 2010.
  10. Lemmers, Richard (19 August 2010). "A Unifying Genetic Model for Facioscapulohumeral Muscular Dystrophy". Science. 329 (5999): 1650–3. doi:10.1126/science.1189044. PMID 20724583. Unknown parameter |coauthors= ignored (help)
  11. Jenkins, Simon P.R. (2005). Sports Science Handbook:I - Z. Brentwood, Essex: Multi-Science Publ. Co. p. 121. ISBN 0906522-37-4.
  12. Turner, C (2010). "The myotonic dystrophies: diagnosis and management". J Neurol Neurosurg Psychiatry. 81: 358–367. doi:10.1136/jnnp.2008.158261. PMID 20176601. Unknown parameter |coauthors= ignored (help)
  13. Medline Plus Medical Encyclopedia Retrieved 8 May 2007.
  14. Centres for Disease Control and Prevention Retrieved 8 May 2007.
  15. Living with Cerebral Palsy Retrieved 8 May 2007.
  16. Jain Foundation Inc: Research into Miyoshi/LGMD2B
  17. H.R. 717--107th Congress (2001): MD-CARE Act, GovTrack.us (database of federal legislation), (accessed Jul 29, 2007)
  18. Public Law 107-84, PDF as retrieved from NIH website


Template:Muscular Dystrophy Template:PNS diseases of the nervous system Template:SIB da:Muskelsvind de:Muskeldystrophie fa:دیستروفی عضلانی it:Distrofia muscolare nl:Ziekte van Duchenne no:Duchenne muskeldystrofi

Template:WH Template:WS