Muscular dystrophy

Template:Short description Template:Infobox medical condition (new) Muscular dystrophies (MD) are a genetically and clinically heterogeneous group of rare neuromuscular diseases that cause progressive weakness and breakdown of skeletal muscles over time.<ref name=NIH2016/> The disorders differ as to which muscles are primarily affected, the degree of weakness, how fast they worsen, and when symptoms begin.<ref name=NIH2016/> Some types are also associated with problems in other organs.<ref name="NIH2016Re">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Over 30 different disorders are classified as muscular dystrophies.<ref name=NIH2016/><ref name=NIH2016Re/> Of those, Duchenne muscular dystrophy (DMD) accounts for approximately 50% of cases and affects males beginning around the age of four.<ref name=NIH2016/> Other relatively common muscular dystrophies include Becker muscular dystrophy, facioscapulohumeral muscular dystrophy, and myotonic dystrophy,<ref name=NIH2016/> whereas limb–girdle muscular dystrophy and congenital muscular dystrophy are themselves groups of several – usually extremely rare – genetic disorders.

Muscular dystrophies are caused by mutations in genes, usually those involved in making muscle proteins.<ref name="NIH2016Re" /> The muscle protein, dystrophin, is in most muscle cells and works to strengthen the muscle fibers and protect them from injury as muscles contract and relax.<ref>Template:Cite book</ref> 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.<ref>Template:Cite journal</ref> Respiratory and cardiac complications can occur as well. These mutations are either inherited from parents or may occur spontaneously during early development.<ref name="NIH2016Re" /> Muscular dystrophies may be X-linked recessive, autosomal recessive, or autosomal dominant.<ref name="NIH2016Re" /> Diagnosis often involves blood tests and genetic testing.<ref name="NIH2016Re" />

There is no cure for any disorder from the muscular dystrophy group.<ref name="NIH2016" /> Several drugs designed to address the root cause are currently available including gene therapy (Elevidys), and antisense drugs (Ataluren, Eteplirsen etc.).<ref name="NIH2016Re" /> Other medications used include glucocorticoids (Deflazacort, Vamorolone); calcium channel blockers (Diltiazem); to slow skeletal and cardiac muscle degeneration, anticonvulsants to control seizures and some muscle activity, and Histone deacetylase inhibitors (Givinostat) to delay damage to dying muscle cells.<ref name="NIH2016" /> Physical therapy, braces, and corrective surgery may help with some symptoms<ref name="NIH2016" /> while assisted ventilation may be required in those with weakness of breathing muscles.<ref name="NIH2016Re" />

Outcomes depend on the specific type of disorder.<ref name=NIH2016>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Many affected people will eventually become unable to walk<ref name=NIH2016Re/> and Duchenne muscular dystrophy in particular is associated with shortened life expectancy.

Muscular dystrophy was first described in the 1830s by Charles Bell.<ref name="NIH2016Re" /> The word "dystrophy" comes from the Greek dys, meaning "no, un-" and troph- meaning "nourish".<ref name="NIH2016Re" />

Signs and symptoms

File:Gould Pyle 216.jpg

Severe limb deformities and contractures indicative of muscular dystrophy

The signs and symptoms consistent with muscular dystrophy are:<ref>Template:EMedicine</ref>Template:Columns-list

Causes

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.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref><ref>Template:Cite bookTemplate:Page needed</ref>

Diagnosis

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.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

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.<ref>Template:Cite journal</ref>

Classification

Disorder name	OMIM	Gene	Inheritance pattern	Age of onset	Muscles affected	Description
Becker muscular dystrophy	none	{{#switch:none	short = OMIM:	shortlink = OMIM:	plain = Online Mendelian Inheritance in Man:	full	#default = Online Mendelian Inheritance in Man (OMIM):}}}} {{#if: | - }} 300376	DMD	XR	Childhood	Distal limbs progressing to generalised weakness	A less severe variant of Duchenne muscular dystrophy,<ref name="2006 report to Congress">May 2006 report to Congress Template:Webarchive on Implementation of the MD CARE Act, as submitted by Department of Health and Human Service's National Institutes of Health</ref> affects predominantly boys.
Congenital muscular dystrophy	Multiple	Multiple	AD, AR	At birth	Generalised 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.<ref>Template:EMedicine</ref> 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.<ref name="2006 report to Congress" />
Duchenne muscular dystrophy	none	{{#switch:none	short = OMIM:	shortlink = OMIM:	plain = Online Mendelian Inheritance in Man:	full	#default = Online Mendelian Inheritance in Man (OMIM):}}}} {{#if: | - }} 310200	DMD	XR	Childhood	Distal limbs progressing to generalised weakness, involving respiratory muscles	citation	CitationClass=web }}</ref> Typical lifespans range from 15 to 45.<ref name="MedlinePlusEncyclopedia000705" /> Sporadic mutations in this gene occur frequently.<ref>{{#invoke:citation/CS1|citation	CitationClass=web }}</ref>
Distal muscular dystrophy	none	{{#switch:none	short = OMIM:	shortlink = OMIM:	plain = Online Mendelian Inheritance in Man:	full	#default = Online Mendelian Inheritance in Man (OMIM):}}}} {{#if: | - }} 254130	DYSF	AD, AR	20–60 years	Distal muscles in hands, forearms and lower legs	Progress is slow and not life-threatening.<ref>Template:Cite book</ref> 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.<ref name="2006 report to Congress" />
Emery–Dreifuss muscular dystrophy	Multiple	Multiple	XR, AD, AR	Childhood, early teenage years	Distal limb muscles, limb-girdle, heart	citation	CitationClass=web }}</ref><ref>{{#invoke:citation/CS1|citation	CitationClass=web }}</ref>
Facioscapulohumeral muscular dystrophy	none	{{#switch:none	short = OMIM:	shortlink = OMIM:	plain = Online Mendelian Inheritance in Man:	full	#default = Online Mendelian Inheritance in Man (OMIM):}}}} {{#if: | - }} 158900	DUX4	AD	Adolescence	Face, shoulders, upper arms, progressing to other muscles	citation	CitationClass=web }}</ref> Affected individuals can become severely disabled, with 20% requiring a wheelchair by age 50.<ref name="FSHD 2016 Review Article">Template:Cite journal</ref> 30% of cases involve spontaneous mutations.<ref name="FSHD 2016 Review Article" /> Penetrance and severity seem to be lower in females compared to males.<ref name="FSHD 2016 Review Article" /><ref>{{#invoke:citation/CS1|citation	CitationClass=web }}</ref>
Limb–girdle muscular dystrophy	Multiple	Multiple	AD, AR	Any	Upper arms and legs	The person normally leads a normal life with some assistance. Rare cardiopulmonary complications can be life-threatening.<ref>Template:Cite book</ref>
Myotonic muscular dystrophy	none	{{#switch:none	short = OMIM:	shortlink = OMIM:	plain = Online Mendelian Inheritance in Man:	full	#default = Online Mendelian Inheritance in Man (OMIM):}}}} {{#if: | - }} 160900Template:Break{{#ifeq:none|none	{{#switch:none	short = OMIM:	shortlink = OMIM:	plain = Online Mendelian Inheritance in Man:	full	#default = Online Mendelian Inheritance in Man (OMIM):}}}} {{#if: | - }} 602668	DMPKTemplate:BreakCNBP	AD	Adulthood	Skeletal muscles, heart, other muscle groups	Presents with myotonia (delayed relaxation of muscles), as well as muscle wasting and weakness.<ref name="Turner">Template:Cite journal</ref> Varies in severity and manifestations and affects many body systems in addition to skeletal muscles, including the heart, endocrine organs, and eyes.<ref>Template:Cite book</ref>
Oculopharyngeal muscular dystrophy	none	{{#switch:none	short = OMIM:	shortlink = OMIM:	plain = Online Mendelian Inheritance in Man:	full	#default = Online Mendelian Inheritance in Man (OMIM):}}}} {{#if: | - }} 164300	PABPN1	AD, rarely AR	40–50 years	Eye muscles, face, throat, pelvis, shoulders

Management

File:Ankle Foot Orthosis leg brace worn on the left foot with ankle hinge.jpg

Ankle foot orthosis

Currently, there is no cure for muscular dystrophy. In terms of management, physical therapy, occupational therapy, orthotic intervention (e.g., ankle-foot orthosis),<ref name=nih2/><ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> speech therapy, and respiratory therapy may be helpful.<ref name="nih2">{{#invoke:citation/CS1|citation |CitationClass=web }}</ref> Low intensity corticosteroids such as prednisone, and deflazacort may help to maintain muscle tone.<ref>Template:Cite journal</ref> Orthoses (orthopedic appliances used for support) and corrective orthopedic surgery may be needed to improve the quality of life in some cases.<ref name=NIH2016Re/> The cardiac problems that occur with Emery–Dreifuss muscular dystrophy (EDMD) and myotonic muscular dystrophy may require a pacemaker.<ref>Template:Cite journal</ref> The myotonia (delayed relaxation of a muscle after a strong contraction) occurring in myotonic muscular dystrophy may be treated with medications such as quinine.<ref>Template:Cite bookTemplate:Page needed</ref>

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.<ref>Template:Cite journal</ref>

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.<ref>Template:Cite book</ref>

Prognosis

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.<ref name=NIH2016Re/>

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,<ref>Template:Cite journal</ref> 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.<ref>{{#invoke:citation/CS1|citation |CitationClass=web }}</ref>

Society and culture

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.<ref>Template:Cite journal</ref>

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.<ref name="govtrack">H.R. 717--107th Congress (2001) Template:Webarchive: MD-CARE Act, GovTrack.us (database of federal legislation), (accessed Jul 29, 2007)</ref><ref name="PL107-84">Public Law 107-84 Template:Webarchive, PDF as retrieved from NIH website</ref>

Research and Advocacy

The Muscular Dystrophy Association (MDA) is involved in research, advocacy, and services for individuals affected by muscular dystrophy. The organization provides resources that contribute to understanding and addressing this condition.

Further reading

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