v Muscular dystrophy (MD) is a group of
muscle diseases that results in increasing weakening and breakdown of skeletal
muscles over time. The disorders differ in which muscles are primarily
affected, the degree of weakness, how fast they worsen, and when symptoms begin
Many people will eventually become unable to walk.
v There are nine main categories of
muscular dystrophy that contain more than thirty specific types.
v The most common type is Duchenne
muscular dystrophy (DMD) which typically affects males beginning around the age
of four.
v Other types include Becker muscular
dystrophy, facioscapulohumeral muscular dystrophy, and myotonic dystrophy.
v They are due to mutations in genes
that are involved in making muscle proteins. This can occur due to either
inheriting the defect from one's parents or the mutation occurring during early
development. Disorders may be X-linked recessive, autosomal recessive, or
autosomal dominant. Diagnosis often involves blood tests and genetic testing.
v There is no cure for muscular
dystrophy. Physical therapy braces, and corrective surgery may help with some
symptoms. Assisted ventilation may be required in those with weakness of
breathing muscles. Medications used include steroids to slow muscle
degeneration, anticonvulsants to control seizures and some muscle activity, and
immunosuppressants to delay damage to dying muscle cells. Outcomes depend on the
specific type of disorder.
v Duchenne muscular dystrophy, which
represents about half of all cases of muscular dystrophy, affects about one in
5,000 males at birth. Muscular dystrophy was first described in the 1830s by
Charles Bell. The word "dystrophy" is from the Greek dys, meaning
"difficult" and troph meaning "nourish". Gene therapy, as a
treatment, is in the early stages of study in humans.
• Signs and symptoms
The signs and symptoms consistent with muscular dystrophy are:
Ø Progressive muscular wasting
Ø Poor balance
Ø Scoliosis (curvature of the spine and
the back)
Ø Progressive inability to walk
Ø Waddling gait
Ø Calf deformation
Ø Limited range of movement
Ø Respiratory difficulty
Ø Cardiomyopathy
Ø Muscle spasms
Ø Gowers' sign
v Cause-
These conditions are generally inherited, and the different
muscular dystrophies follow various inheritance patterns. Muscular dystrophy
can be inherited by individuals as an X-linked disorder, a recessive or
dominant disorder. Furthermore, it can be a spontaneous mutation which means
errors in the replication of DNA and spontaneous lesions. Spontaneous lesions
are due to natural damage to DNA, where the most common are depurination and
deamination.
Dystrophin protein is found in muscle fibre membrane; its helical
nature allows it to act like a spring or shock absorber. Dystrophin links
actinin the cytoskeleton and dystroglycans of the muscle cell plasma membrane,
known as the sarcolemma (extracellular). In addition to mechanical
stabilization, dystrophin also regulates calcium levels.
v Becker muscular dystrophy
DMD Becker muscular
dystrophy (BMD) is a less severe variant of Duchenne muscular dystrophyand is
caused by the production of a truncated, but partially functional form of
dystrophin. Survival is usually into old age and affects only boys (with
extremely rare exceptions)
v Congenital muscular dystrophy
Age at onset is birth, the 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.
v Duchenne muscular dystrophy
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 unable to walk. Lifespans
range from 15 to 45, though a few exceptions occur. Researchers have 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.
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.
v Distal muscular dystrophy
Distal muscular dystrophies' age at onset is about 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.
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.
v Emery–Dreifuss muscular dystrophy
Emery–Dreifuss muscular dystrophy patients normally present
in childhood and the early teenaged 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.
v Facioscapulohumeral muscular dystrophy
Timelapse expression of DUX4 protein in FSHD cells
Facioscapulohumeral muscular dystrophy (FSHD) initially
affects the muscles of the face, shoulders, and upper arms with progressive weakness.
Symptoms usually develop in early adulthood (late teens);
affected individuals become severely disabled. The pattern of inheritance is
autosomal dominant, though a number of spontaneous mutations occur. Two defects
are needed for FSHD, which for the first time provides a unifying theory for
the underlying genetics of FSHD.
FSHD occurs both in males and females.
v Limb-girdle muscular dystrophy
Multiple Multiple Limb-girdle muscular dystrophy (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 teenaged 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. Though a person normally leads a normal
life with some assistance, in some extreme cases, death from LGMD occurs due to
cardiopulmonary complications.
v Myotonic muscular dystrophy
Myotonic muscular dystrophy is an autosomal dominant
condition that presents with myotonia (delayed relaxation of muscles), as well
as muscle wasting and weakness.Myotonic MD varies in severity and
manifestations and affects many body systems in addition to skeletal muscles,
including the heart, endocrine organs, and eyes.
Myotonic MD type 1 (DM1) 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 myotonic dystrophy protein kinase gene. Myotonic
muscular dystrophy type 2 (DM2) is rarer and is a result of the expansion of
the CCTG repeat in the zinc finger protein 9 gene.
v Oculopharyngeal muscular dystrophy
Oculopharyngeal MD's age at onset is 40 to 70 years; symptoms
affect muscles of eyelids, face, and throat followed by pelvic and shoulder
muscle weakness; it has been attributed to a short repeat expansion in the
genome which regulates the translation of some genes into functional proteins.
v 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.
Other tests that can be done are chest X-ray, echocardiogram,
CT scan, and magnetic resonance image scan, which via a magnetic field can produce
images whose detail helps diagnose muscular dystrophy.
