1. Duchenne Muscular Dystrophy
BRIAN CHANDA CHILUBA
Dip.PT; Cert. NDT
NEUROLOGY CLASS PRESENTATION

2. Overview Basic information about Duchenne muscular dystrophy
Inheritance
Prevalence
Symptoms
Treatments
Topics covered in this PowerPoint include an introduction to a form of muscular dystrophy known as Duchenne muscular dystrophy (DMD), and a brief review of inheritance, prevalence, symptoms, and treatment of DMD.

3. What Is Duchenne Muscular Dystrophy?(1)
Genetic
Progressive muscle weakness
Defects in muscle proteins
Death of muscle tissue
This presentation will discuss a form of muscular dystrophy called Duchenne muscular dystrophy. Duchenne muscular dystrophy is a genetic or hereditary muscle condition; characterized by progressive skeletal muscle weakness, defects in muscle proteins, and the death of muscle cells and tissue.
In DMD, absence of the dystrophin protein weakens the connections between all of the proteins in the muscle and the cell membrane. Eventually the cell membrane becomes weaker and ruptures. As a result, particles, such as calcium, can move in and out of the ruptured cell membrane. As calcium moves into the muscle cell, it will cause contraction at the damaged site and muscle fibers will break. When this is severe enough, the muscle will begin to waste away. (1)

4. MUSCULAR DYSTROPHY
Muscular dystrophies - group of genetic conditions characterized by progressive muscle weakness and wasting (atrophy)
20 different types of muscular dystrophy exist
(DMD) is named after the French neurologist Guillaume Benjamin Amand Duchenne (1806–1875), who first described the disease in 1861
Guillaume Benjamin Amand Duchenne-1861 described the disease DMD.
There are 20 different types of Muscular Dystrophy, the most common being DMD and BMD - (Bechers Muscular Dystrophy)

5. DMD
(DMD) is a severe recessive X-linked form of muscular dystrophy characterized by rapid progression of muscle degeneration, eventually leading to loss of ambulation and death
DMD is caused by a defective gene for dystrophin (a protein in the muscles) or by mutations in the dystrophin gene, which is located on the X chromosome

6. DMD
DMD absence of the dystrophin protein weakens the connections between all of the proteins in the muscle and the cell membrane
cell membrane becomes weaker and ruptures
particles, such as calcium, can move in and out of the ruptured cell membrane

7. Where is This Gene?
The gene for dystrophin production sits on the X chromosome. If a normal gene for dystrophin is present, then the protein will be made. If the gene is missing or altered, dystrophin may not be produced at all or only in abnormal forms, resulting in Duchenne muscular dystrophy. (1)
Graphic used with permission from the National Center for Biotechnology Information, The National Library of Medicine, The National Institutes of Health, Department of Health and Human Services:
Genes and Disease [online] [cited 2005 June 26]. Available from URL:

8. PHYSIOLOGY OF DYSTROPHIN
The dystrophin molecule anchors the cytoskeleton of muscle cells to the extracellular matrix, via the dystrophin glycoprotein complex.
This includes the sarcoglycans (mutations in which cause limb-girdle muscular dystrophies) and dystroglycans.
Muscle cells that lack dystrophin are mechanically fragile, and fail after a few years, hence progressive muscle weakness.

9. Duchenne Muscular Dystrophy Inheritance(1)
Mother carries the recessive gene and passes it to her child
Trait is usually expressed in
males only
Since the gene for DMD is carried on the X chromosome, it is usually the mother that passes the condition on to her children. A female with one recessive copy of the gene for DMD is called a carrier. She still has one normal copy of the gene for dystrophin production, and she will usually show no signs of the condition. A female with two recessive copies of the gene will have the condition. Some female carriers may have mild symptoms of the disorders, and in rare cases they may have full DMD – this is due to skewed X-inactivation patterns.
Since a male only has one X chromosome, if he has the recessive copy of the gene present, he will have the condition. Males may only pass the recessive copy of the gene on to their offspring if they have the condition themselves.
In the Punnet Square provided in the link, a female carrier and a male without the recessive gene have children. If their child is a female, shown in pink, there is 1/2 chance that she will be a carrier of DMD. If their child is a male, there is 1/2 chance that he will have the condition. (1)
(This pattern of inheritance is only true for X-linked muscular dystrophies like DMD and Emery-Drieffus. Other muscular dystrophies are inherited in different ways.)
Punnett Square Link:
MedlinePlus Medical Encyclopedia [online] [cited 2005 June 26]. Available from URL:

10. Prevalence of DMD(1) Affects one in 3500 to 5000 newborn males
1/3 of these with previous family history
2/3 sporadic
Duchenne Becker Muscular dystrophy affects about one in every 3500 to 5000 newborn males.
One third of these boys have a previous relative with DMD. Two thirds of the cases are sporadic. There are two groups that make up the sporadic cases. In 1/3 of cases (or ½ of the sporadic cases), there was a genetic mutation in the mother’s egg or a genetic mutation early in embryo development that led to the condition. In the other 1/3 of cases (other ½ of sporadic cases), the mother is a carrier, but she is carrying a new mutation that occurred in either her mother’s egg, her father’s sperm, or early in her development. This explains the cases where a boy is born with Duchenne Becker muscular dystrophy into a family with absolutely no history of the condition. (1)
Graphic citation:
Microsoft Office Clipart [cited 23 June, 2005].
Hilda, this is from Katherines presentation. She had a similar slide and I took notes as she talked. I think that someone even asked about sporadic….

11. Symptoms of DMD(1) Symptoms usually appear before age 6
Delayed developmental milestones
Loss of motor skills
Characteristic gait
Calf hypertrophy
Clumsiness/frequent falls
Symptoms usually begin to occur around 2-3 years of age. The boys may show delayed developmental milestones. For example, they are not sitting up or crawling when other boys their age begin.
Loss of motor skills may be apparent. Once they begin to walk, it may become more difficult as time goes on.
Boys tend to have a characteristic gait shown by walking on their toes. The Achilles' tendon becomes tight because of the muscle contraction in the calf and it is uncomfortable to bring the heel down. The calves will appear larger (hypertrophy). This is due to the loss of muscle being replaced with fat and connective tissue.
Finally, as the muscles weaken, the boys may appear clumsy and fall frequently. (1)

12. More Symptoms of DMD(1) Muscle weakness
Difficulty climbing stairs or hills
Difficulty rising (Gower’s sign)
Difficulty walking/running
As the boy gets older, muscle weakness will become apparent. The calf muscles are the first to weaken, so walking up stairs or hills becomes difficult.
Gower’s sign is used in diagnosing the condition. This symptom shows the boy using his arms to get up from a sitting position because the leg muscles are too weak to allow for the task. (Click on the link and scroll down to Figure 2 to see Gower’s sign).
Finally, walking and running will become difficult. (1)
Link to Gower’s sign via the internet:
Kalra, V. Childhood Muscular Dystrophies [online] [cited 2005 June 26]. Available from URL:

13. GOWERS SIGN

14. PROGNOSIS
Duchenne muscular dystrophy leads to quickly worsening disability. Death usually occurs by age 25, typically from lung disorders

15. Treatments for DMD (1) To improve breathing: O2 therapy Ventilator
Scoliosis surgery
Tracheotomy
Once the condition has progressed, it will begin to affect all the muscles in the body. People with muscular dystrophy may begin to slump due to decreased muscle control in the back. When this happens, breathing will be more difficult because of decreased lung capacity. Scoliosis, which is a curvature of the spine, might also develop due to decreased muscle control. Treatments for breathing include oxygen therapy, ventilator use, scoliosis surgery to correct the spine, and even a tracheotomy if symptoms are severe. (1)
Graphic used with permission from the Scoliosis Association, Inc. [online] [cited 2005 June 26]. Available at URL:

16. Treatments (cont.) (1) To improve mobility: Physical therapy
Surgery on tight joints
Prednisone-ppppppppppppppppppppp
Non-steroidal medications-oooooo
Wheelchair
Physical therapy will help to keep the muscles in shape and agile. A physical therapist will work the muscles that are most affected by the condition. As muscle contraction occurs, the joints may become tight. Surgery on the joints to relieve the tension may be performed. Prednisone is a catabolic steroid that actually breaks muscle down. It also is an anti-inflammatory that helps slow down the aggregation of lymphocytes and fat cells in muscles. This seems to help delay the effects of the condition, although doctors are unsure of how this works yet. There are symptoms that go along with the use of prednisone. They include weight gain and mood alteration. These could lead to other problems, such as decreased activity due to weight gain. The use of prednisone is carefully evaluated. Non-steroidal medications are used to treat cardiac disorders, constipation, depression and osteoporosis. As the condition worsens, people with muscular dystrophy might feel that walking is too difficult. At this point, they might decide that a wheelchair gives them more freedom of movement. (1)
Graphics citation:
Microsoft Office Clipart [cited 23 June, 2005].

17. PHYSIOTHERAPY TREATMENT
AIM TO :
minimize the development of contractures and deformity by developing a program of stretches and exercises where appropriate
anticipate and minimize other secondary complications of a physical nature
monitor respiratory function and advise on techniques to assist with breathing exercises and methods of clearing secretions

18. The Beginning of Gene Therapy
for DMD (2)
Current research focuses on gene therapy to cure DMD. This article from 1998 shows researchers Chamerlain and Giovanni as they worked to deliver the dystrophin gene into the body of mice without triggering the immune system. (2)
Graphics used with permission from Pobojewski, S. The University Record, November 9, U-M’s improved viral vector delivers dystrophin gene to mouse muscle without major immune
Response [online] [cited 2005 June 26]. Available at URL:

19. Advances in Gene Therapy(3)
Researches have developed "minigenes," which carry instructions for a slightly smaller version of dystrophin, that can fit inside a virus
Researchers have also created the so-called gutted virus, a virus that has had its own genes removed so that it is carrying only the dystrophin gene
The dystrophin gene is the largest known gene. It numbers 2.3 million base pairs. This is a large gene to insert into a virus to deliver to the muscle. Researchers have developed “minigenes” or smaller versions of the dystrophin gene that seem to fit better into the virus.
They have also developed the gutted virus, which is a hollow virus that only carries the dystrophin gene. (3)

20. Problems with Gene Therapy(3)
Muscle tissue is large and relatively impenetrable
Viruses might provoke the immune system and cause the destruction of muscle fibers with the new genes
Even with the advances that have been made, there are still problems with gene therapy. The muscle tissue that would need to have the gene inserted is large and difficult to penetrate.
It is possible that with the insertion of viruses into the muscle tissue, an immune response could be mounted to kill the “invading” virus. Also, the body may mount an immune attack against dystrophin, which the body will see as “foreign.” Unfortunately, this means that muscle cells with the new gene would be destroyed. (3)

21. COMPLICATIONS Cardiomyopathy Congestive heart failure (rare)
Deformities
Heart arrhythmias (rare)
Mental impairment (varies, usually minimal)
Permanent, progressive disability
Decreased mobility
Decreased ability to care for self
Pneumonia or other respiratory infections
Respiratory failure

22. References:
1. “Muscular Dystrophy” PowerPoint by Katherine Kolor, PhD, MS, CDC Ambassador Program, June 2005.
2. Pobojewski, S. The University Record, November 9, U-M’s improved viral vector delivers dystrophin gene to mouse muscle without major immune Response [online] [cited 2005 June 26]. Available at URL:
3. Journey of Love: A Parent’s Guide to Duchenne Muscular Dystrophy [online] [cited 2005 June 22]. Available from URL:
4. Dictionary.com. Lexico Publishing Group, LLC. [online] [cited 2005 June 22]. Available from URL: