Muscular dystrophy

From Wikipedia, the free encyclopedia

Muscular Dystrophy

Classification and external resources

In affected muscle the tissue becomes disorganized and the concentration

ofdystrophin (green) is greatly reduced.

ICD-10 G71.0

ICD-9 359.0-359.1

MedlinePlus 001190

eMedicine orthoped/418

MeSH D009136

Muscular Dystrophy (MD) is a group of muscle diseases that weaken the musculoskeletal system and

hamper locomotion.[1][2] Muscular dystrophies are characterized by progressive skeletal muscle weakness,
defects in muscle proteins, and the death of muscle cells and tissue.[3]

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. The other major forms are Becker, limb-

girdle, congenital, facioscapulohumeral,myotonic, oculopharyngeal, distal, and Emery-Dreifuss muscular

dystrophy.[4] These diseases predominantly affect males, although females may be carriers of the disease

gene. Most types of MD are multi-system disorders with manifestations in body systems including the heart,

gastrointestinal system, nervous system, endocrine glands, eyes and brain.[4]

 Apart from the nine major types of muscular dystrophy listed above, several MD-like conditions have also

been identified. Normal intellectual, behavioral, bowel and sexual function is noticed in individuals with other

forms of MD and MD-like conditions.[5][6] MD-affected individuals with susceptible intellectual impairment are

diagnosed through molecular characteristics but not through problems associated with disability.[7] However,

a third of patients who are severely affected with DMD may have cognitive impairment, behavioral, vision

and speech problems.[8][9]

Contents

[hide]

 1 Signs and symptoms

 2 Cause
 3 Diagnosis

 4 Management

 5 Prognosis

 6 Types

 7 Research funding

 8 See also

 9 References

 10 External links

Signs and symptoms[edit source | editbeta]

 Progressive muscular wasting

 Poor balance

 Drooping eyelids

 Atrophy

 Scoliosis (curvature of the spine and the back)

 Inability to walk

 Frequent falls

 Waddling gait

 Calf deformation

 Limited range of movement

 Respiratory difficulty

 Joint contractures

 Cardiomyopathy
 Arrhythmias

 Muscle spasms

Cause[edit source | editbeta]

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

patterns. However, mutations of the dystrophin gene and nutritional defects (with no genetics history) at the

prenatal stage are also possible in about 33% of people affected by DMD.[10] The main cause of the

Duchenne and Becker types of muscular dystrophy is the muscle tissue's cytoskeletal impairment to

properly create the functional protein dystrophin and dystrophin-associated protein complex.

Dystrophin protein is found in muscle fibre membrane; its helical nature allows it to act like a spring or shock

absorber. Dystrophin links actin (cytoskeleton) and dystroglycans of the muscle cell plasma membrane,

known as the sarcolemma (extracellular). In addition to mechanical stabilization, dystrophin also regulates

calcium levels.[citation needed]

Diagnosis[edit source | editbeta]

Histopathology of gastrocnemius muscle from patient who died of pseudohypertrophic muscular dystrophy, Duchenne

type. Cross section of muscle shows extensive replacement of muscle fibers by adipose cells.

The diagnosis of muscular dystrophy is based on the results of muscle biopsy, increased creatine

phosphokinase (CpK3), electromyography,electrocardiography and DNA analysis.

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.

Management[edit source | editbeta]

There is no known cure for muscular dystrophy, although significant headway is being made with antisense

oligonucleotides.[11] Physical therapy,occupational therapy, orthotic intervention (e.g., ankle-foot orthosis),

speech therapy and orthopedic instruments (e.g., wheelchairs and standing frames) may be helpful.

Inactivity (such as bed rest, sitting for long periods) and bodybuilding efforts to increase myofibrillar

hypertrophy can worsen the disease.

There is no specific treatment for any of the forms of muscular dystrophy. Physiotherapy, aerobic exercise,

low intensity anabolic steroids, prednisonesupplements may help 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.[12]

High dietary intake of lean meat, sea food, pulses, olive oil, antioxidants; such as leafy vegetables and bell

peppers, and fruits like blueberry, cherry etc. is advised. Decreased intake of refined food, trans-fats, and

caffeinated and alcoholic beverages is also advised; as is a check for any food allergies.[13]

Diagnosis, neurology, GI-nutrition, respiratory care, cardiac care, orthopedics, psychosocial, rehabilitation,

and oral care form the integral part of disease management, all through the patient's life span.

Prognosis[edit source | editbeta]

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.

Types[edit source | editbeta]

Type OMIM Gene Description

Becker's muscular 300376 DMD Becker muscular dystrophy (BMD) is a less severe variant
dystrophy 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.[14] Affects
only boys (with extremely rare exceptions)

Age at onset: birth; symptoms include general muscle

weakness and possible joint deformities; disease
progresses slowly; shortened life span.[15]

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
Congenital muscular
Multiple Multiple on the brain and other organ systems. A number of the
dystrophy
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 310200 DMD Duchenne muscular dystrophy (DMD) is the most
dystrophy 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.[16] Patients usually die around age 25, but this
depends from person to person.[16] 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 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.[14]

Distal muscular Miyoshi myopathy, one of the distal muscular dystrophies,

254130 DYSF
dystrophy
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

Emery-Dreifuss Dystrophy, distinguishable by their pattern of inheritance:

310300,181350 EMD,LMNA
muscular dystrophy
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.[17]

Facioscapulohumeral 158900 DUX4 Facioscapulohumeral muscular dystrophy (FSHD) initially

muscular dystrophy 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][18]
 [19]

Facioscapulohumeral muscular dystrophy (FSHD) occurs

both in males and females.

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
Limb-girdle muscular copies of the defective gene, one from each parent. The
Multiple Multiple
dystrophy 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.[20]
Myotonic muscular dystrophy is an autosomal dominant
condition that presents with myotonia (delayed relaxation
of muscles) as well as muscle wasting and weakness.
[21]
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
Myotonic muscular
160900,602668 DMPK,ZNF9
dystrophy 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 MD's age at onset: 40 to 70 years;

symptoms affect muscles of eyelids, face, and throat
Oculopharyngeal followed by pelvic and shoulder muscle weakness, has
164300 PABPN1
muscular dystrophy been attributed to a short repeat expansion in
the genome which regulates the translation of some genes
into functional proteins.[4]
Spina bifida (Latin: "split spine") is a developmental congenital disorder caused by the incomplete
closing of the embryonic neural tube. Somevertebrae overlying the spinal cord are not fully formed and
remain unfused and open. If the opening is large enough, this allows a portion of the spinal cord to
protrude through the opening in the bones. There may or may not be a fluid-filled sac surrounding the
spinal cord. Other neural tube defects include anencephaly, a condition in which the portion of the
neural tube that will become the cerebrum does not close, and encephalocele, which results when
other parts of the brain remain unfused.

Spina bifida malformations fall into three categories: spina bifida occulta, spina bifida cystica with
meningocele, and spina bifida cystica with myelomeningocele. The most common location of the
malformations is the lumbar and sacral areas. Myelomeningocele is the most significant and common
form, and this leads to disability in most affected individuals. The terms spina bifida and
myelomeningocele are usually used interchangeably.

Spina bifida can be surgically closed after birth, but this does not restore normal function to the
affected part of the spinal cord. Intrauterine surgery for spina bifida has also been performed, and the
safety and efficacy of this procedure are currently being investigated. A study conducted with mothers
who had prior spina bifida births indicates the incidence of spina bifida can be decreased by up to 70%
when the mother takes daily folic acidsupplements prior to conception.

Spina bifida is one of the most common birth defects with a worldwide incidence of about 1 in every
1000 births

Meningocele[edit source | editbeta]

The least common form of spina bifida is a posterior meningocele (or meningeal cyst). In this form, the
vertebrae develop normally, but the meninges are forced into the gaps between the vertebrae. As the
nervous system remains undamaged, individuals with meningocele are unlikely to suffer long-term
health problems, although cases of tethered cord have been reported. Causes of meningocele
include teratoma and other tumors of the sacrococcyxand of the presacral space, and Currarino
syndrome.

A meningocele may also form through dehiscences in the base of the skull. These may be classified by
their localisation to occipital, frontoethmoidal, or nasal. Endonasal meningoceles lie at the roof of
the nasal cavity and may be mistaken for a nasal polyp. They are treated surgically.
Encephalomeningoceles are classified in the same way and also contain brain tissue.

Myelomeningocele[edit source | editbeta]

This type of spina bifida often results in the most severe complications. [11] In individuals with
myelomeningocele, the unfused portion of the spinal column allows the spinal cord to protrude through
an opening. The meningeal membranes that cover the spinal cord form a sac enclosing the spinal
elements.

Myeloschisis[edit source | editbeta]

Spina bifida with myeloschisis is the most severe form of myelomeningocele. In this type, the involved
area is represented by a flattened, plate-like mass of nervous tissue with no overlying membrane. The
exposure of these nerves and tissues make the baby more prone to life-threatening infections such
as meningitis.[12]
The protruding portion of the spinal cord and the nerves that originate at that level of the cord are
damaged or not properly developed. As a result, there is usually some degree of paralysis and loss of
sensation below the level of the spinal cord defect. Thus, the more cranial the level of the defect, the
more severe the associated nerve dysfunction and resultant paralysis may be. People may have
ambulatory problems, loss of sensation, deformities of the hips, knees or feet, and loss of muscle tone.

Treatment[edit source | editbeta]

There is no known cure for nerve damage caused by spina bifida. To prevent further damage of the
nervous tissue and to prevent infection, pediatric neurosurgeons operate to close the opening on the
back. The spinal cord and its nerve roots are put back inside the spine and covered with meninges. In
addition, a shunt may be surgically installed to provide a continuous drain for the excess cerebrospinal
fluid produced in the brain, as happens with hydrocephalus. Shunts most commonly drain into
the abdomen or chest wall. However, if spina bifida is detected during pregnancy, thenopen or
minimally-invasive fetal surgery can be performed.[17]

In childhood[edit source | editbeta]

Most individuals with myelomeningocele will need periodic evaluations by a variety of specialists: [49]

 Physiatrists coordinate the rehabilitation efforts of different therapists and prescribe specific
therapies, adaptive equipment, or medications to encourage as high of a functional performance
within the community as possible.
 Orthopedists monitor growth and development of bones, muscles, and joints.
 Neurosurgeons perform surgeries at birth and manage complications associated with
tethered cord and hydrocephalus.
 Neurologists treat and evaluate nervous system issues, such as seizure disorders.
 Urologists to address kidney, bladder, and bowel dysfunction - many will need to manage
their urinary systems with a program of catheterization. Bowel management programs aimed at
improving elimination are also designed.
 Ophthalmologists evaluate and treat complications of the eyes.
 Orthotists design and customize various types of assistive technology, including braces,
crutches, walkers, and wheelchairs to aid in mobility. As a general rule, the higher the level of the
spina bifida defect, the more severe the paralysis, but paralysis does not always occur. Thus,
those with low levels may need only short leg braces, whereas those with higher levels do best
with a wheelchair, and some may be able to walk unaided.