DUCHENNE

MUSCULAR
DYSTROPHY(DMD)
Alan Benny
1840632
6BCZ
 Introduction
◦ Duchenne muscular dystrophy (DMD) is a severe type of muscular
dystrophy that primarily affects boys. Muscle weakness usually begins around
the age of four, and worsens quickly. Muscle loss typically occurs first in the
thighs and pelvis followed by the arms.
◦ This can result in trouble standing up. Most are unable to walk by the age of
12. Affected muscles may look larger due to increased fat content. Scoliosis is
also common. Some may have intellectual disability. Females with a single
copy of the defective gene may show mild symptoms.
◦ The disorder is X-linked recessive. About two thirds of cases
are inherited from a person's mother, while one third of cases are due to a
new mutation. It is caused by a mutation in the gene for
the protein dystrophin.
◦ Dystrophin is important to maintain the muscle fiber's cell membrane. Genetic
testing can often make the diagnosis at birth. Those affected also have a high
level of creatine kinase in their blood.
 History
◦ The disease was first described by the Neapolitan physician Giovanni
Semmola in 1834 and Gaetano Conte in 1836
◦ However, DMD is named after the French neurologist Guillaume-
Benjamin-Amand Duchenne (1806–1875), who in the 1861 edition of
his book Paraplegie hypertrophique de l'enfance de cause cerebrale,
described and detailed the case of a boy who had this condition.
◦ Duchenne was the first to do a biopsy to obtain tissue from a living
patient for microscopic examination.
 Cause
◦ DMD is caused by a mutation of the dystrophin gene
at locus Xp21, located on the short arm of the X chromosome.
◦ The absence of dystrophin permits excess calcium to penetrate
the sarcolemma (the cell membrane).
◦ DMD is inherited in an X-linked recessive pattern.
◦ It can occur in females with an affected father and a carrier mother,
in those who are missing an X chromosome, or those who have an
inactivated X chromosome (the most common of the rare reasons)
 Signs and Symptoms
◦ DMD causes progressive muscle weakness due to muscle
fiber disarray, death, and replacement with connective tissue or
fat.
◦ There is general difficulty with motor skills, which can result in an
awkward manner of walking, stepping, or running.
◦ Cardiomyopathy, particularly dilated cardiomyopathy, is common
◦ In late stages of the disease, respiratory impairment and
swallowing impairment can occur, which can result in pneumonia
◦ A classic sign of DMD is trouble getting up from lying or sitting
position, as manifested by a positive Gowers' sign.
◦ The muscle tissue is eventually replaced by fat and connective
tissue, hence the term pseudohypertrophy.
 Diagnosis
◦ DNA Test:The muscle-specific isoform of the dystrophin gene is
composed of 79 exons, and DNA testing (blood test) and
analysis can usually identify the specific type of mutation of the
exon or exons that are affected. DNA testing confirms the
diagnosis in most cases.
◦ Muscle Biopsy: A small sample of muscle tissue is extracted
using a biopsy needle. The key tests performed on the biopsy
sample for DMD
are immunohistochemistry, immunocytochemistry,
and immunoblotting for dystrophin. Absence of the protein is a
positive test for DMD. Where dystrophin is present, the tests
indicate the amount and molecular size of dystrophin, helping to
distinguish DMD from milder dystrophinopathy phenotypes
◦ Prenatal Test: Prenatal tests can tell whether the unborn child
has one of the most common mutations. This can be achieved
by ultrasound scan at 16 weeks or more recently by free fetal
DNA testing.
Treatment
◦ No cure for DMD is known, and an ongoing medical need has been recognized by regulatory
authorities. Gene therapy has shown some success
◦ Corticosteroids such as prednisolone and deflazacort lead to short-term improvements in
muscle strength and function up to 2 years.
◦ Physical therapy is helpful to maintain muscle strength, flexibility, and function
◦ Appropriate respiratory support as the disease progresses is important.
◦ Cardiac problems may require a pacemaker.
 Research
◦ Exon Skipping: Antisense oligonucleotides (oligos), structural
analogs of DNA, are the basis of a potential treatment for 10% of
people with DMD. The compounds allow faulty parts of the
dystrophin gene to be skipped when it is transcribed to RNA for
protein production, permitting a still-trim but more functional
version of the protein to be produced. It is also known as nonsense
suppression therapy.
◦ Gene Therapy: Researchers are working on a gene editing method
to correct a mutation that leads to Duchenne muscular dystrophy
(DMD). Researchers used a technique called CRISPR/Cas9-
mediated genome editing, which can precisely remove a mutation
in the dystrophin gene in DNA, allowing the body's DNA
repair mechanisms to replace it with a normal copy of the
gene. The benefit of this over other gene therapy techniques is that
it can permanently correct the "defect" in a gene rather than just
transiently adding a "functional" one
Links for Further Reading
◦ https://www.mda.org/disease/duchenne-muscular-dystrophy
◦ https://rarediseases.info.nih.gov/diseases/6291/duchenne-muscular-dystrophy
◦ https://www.webmd.com/children/duchenne-muscular-dystrophy#1
◦ https://medlineplus.gov/ency/article/000705.htm
◦ https://medlineplus.gov/genetics/gene/dmd/
◦ https://www.physio-pedia.com/Duchenne_Muscular_Dystrophy
◦ https://musculardystrophynews.com/muscular-dystrophy-types/what-is-duchenne-muscular-dystrophy/
◦ https://www.fda.gov/news-events/press-announcements/fda-approves-targeted-treatment-rare-duchenne-muscular-
dystrophy-mutation
◦ https://www.mda.org/disease/duchenne-muscular-
dystrophy/research#:~:text=A%20later%20study%20conducted%20in,increased%20muscle%20function%20in%20DMD.