“ LAUNCHPAD ”

1. “LAUNCHPAD” Lindsey Cole, Vanessa Lewis, Leah Weaver

2. Duchenne Muscular Dystrophy

3. Duchenne Muscular Dystrophy (DMD) • What is Duchenne Muscular Dystrophy? • Who does it affect? • What are the causes of this disease? • What are the symptoms of DMD? • How is the disease diagnosed? • How are patients lives affected? • Available treatment options

4. What is Duchenne Muscular Dystrophy? • X-linked genetic disorder • Characterized by progressive muscle loss and weakness • (“muscle-wasting disease”) • Caused by genetic change to the protein Dystrophin

5. Who Does it Affect? • With a few exceptions, males are most commonly affected • Symptoms noticeable in early childhood years (2-3 years old) • Life expectancy early-mid 20’s

6. What causes the disease? • Genetic Causes • X-lined recessive mutation • Usually inherited from a parent who carries the mutation • Can also occur by spontaneous mutation in the egg or sperm (~40% of cases)

7. Can you draw a Punnett Square?

8. A female carrier of the recessive mutation has a 50% chance of passing the trait to a male offspring who will be affected by the mutation. • Female carriers are not affected because adequate dystrophin is produced by their unaffected X-chromosome.

9. Mechanism of the Mutation • On the x chromosome there is a gene that codes for the protein dystrophin • When this gene is mutated, dystrophin will be inadequately produced, thus causing DMD

10. Dystrophin • Protein found in muscle that maintains structural support • It anchors muscle filaments to the cell membrane • When absent a decrease in anchorage occurs causing: • Decreased muscle force • Damage to muscle fiber

11. Progressive muscle loss and weakness (muscle wasting) Decreased muscle strength Progressive curvature of the spine Painful positioning of the joints Enlarged calf muscles Shortening of muscle fibers Difficulty with everyday motor movements i.e. walking, balancing, raising arms Signs/Symptoms of DMD

12. How is DMD diagnosed? • Evaluation of family history • Initial physical exam

13. CK Blood Test • Tests level of enzyme creatine kinase. When muscles are damaged, CK leaks out. High levels of CK in the blood indicate muscle destruction.

14. Muscle Biopsy • Small sample of muscle extracted to indicate missing or abnormal dystrophin

15. DNA Diagnostic Test • Analyzing blood samples provides precise genetic information • This information can: • Identify carriers • Provide pre-natal diagnosis

16. Available Treatment Options • These help alleviate symptoms and slow disease progression • Physical Therapy and Exercise • Prevent or delay curvature of the spine • Help alleviate pain in joints due to abnormal positioning

17. Treatment Options • Corticosteroids • May slow muscle destruction or help control other complications • Examples include: Prednisone, Deflazacort, Albuterol, and Creatine.

18. Treatment Options • Surgery • Usually to treat “Scoliosis” • Sometimes relieves muscle shortening • Can also treat injured joints while patient is still mobile

19. Treatment Options • Rehabilitative Devices • Example: Canes, wheelchairs, and braces • Help patient maintain mobility and independence

20. How are patients lives affected? • Waddling, unsteady gait • Frequent falling • Muscle cramps • Inability to walk by age 7-12 • Usually restricted to wheelchair • Additional abnormalities involving cardiac and respiratory functions

21. Has anyone here ever known someone, or been affected in some way by DMD?

22. References: • Muscular Dystrophy Association Website • Genetics Education Website • Disease Directory • Duchenne Muscular Dystrophy Animal Models and Genetic Manipulation by: Howell, Kakulas, and Roses. New York : Raven Press. (1992).