Duchenne Muscular Dystrophy

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

2. Overview • Basic information about Duchenne muscular dystrophy • Inheritance • Prevalence • Symptoms • Treatments

3. What Is Duchenne Muscular Dystrophy?(1) • Genetic • Progressive muscle weakness • Defects in muscle proteins • Death of muscle tissue

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

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?

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 • Traitis usually expressed in males only

10. Prevalence of DMD(1) • Affects one in 3500 to 5000 newborn males • 1/3 of these with previous family history • 2/3 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

12. More Symptoms of DMD(1) • Muscle weakness • Difficulty climbing stairs or hills • Difficulty rising (Gower’s sign) • Difficulty walking/running

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

16. Treatments (cont.) (1) • To improve mobility: • Physical therapy • Surgery on tight joints • Prednisone-ppppppppppppppppppppp • Non-steroidal medications-oooooo • Wheelchair

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)

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

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

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, 1998. U-M’s improved viral vector delivers dystrophin gene to mouse muscle without major immune Response [online]. 1998. [cited 2005 June 26]. Available at URL:http://www.umihc.edu/~urecord/9899/Nov09_98/12.html 3. Journey of Love: A Parent’s Guide to Duchenne Muscular Dystrophy [online]. 2004. [cited 2005 June 22]. Available from URL: http://www.mdausa.org/publications/journey/5.html 4. Dictionary.com. Lexico Publishing Group, LLC. [online]. 2005. [cited 2005 June 22]. Available from URL: http://dictionary.reference.com/