4. In elderly patients with weakness, mildly elevated CPK does not equal (primary) myopathy!

5. Neurogenic V. Myopathic

7. Endomysial fibrosis = Muscular dystrophy

8. Dystrophin Dystrophin Actin -Largest known gene, by far (the average gene consists of 3000 bases; the dystrophin gene comprises 2.4 million) -Short arm of X chromosome

11. Duchenne muscular dystrophy Dystrophin Actin

12. Duchenne muscular dystrophy Actin

13. Duchenne muscular dystrophy Actin

14. Duchenne muscular dystrophy Actin

15. Dystrophin: Duchenne muscular dystrophy “ Revertant fibers” result from reading frame restoring mutations

16. Becker muscular dystrophy Dystrophin Actin -Dystrophin present, but abnormally short due to in-frame deletions -Variety of clinical presentations and progressions, most involving at least some degree of proximal weakness

17. Dystrophin: Becker muscular dystrophy Immunohistochemical staining is non-specific!

21. How dysferlin works Dystrophin Actin

22. Dystrophin Actin

23. Dystrophin Actin

24. Dystrophin Actin

25. Polymyositis “ Invasion of non-necrotic fibers”

26. Dermatomyositis

27. DM = Complement mediated, small vessel vasculitic myopathy

31. IBM: Pathologic diagnosis

35. SMI-31 Immunostaining

38. Stochastic segregation during cell division results in tissue and cellular heteroplasmy

39. Heteroplasmy results in a threshold effect , both clinically and pathologically

40. Cellular heteroplasmy/threshold effect

41. Developmental heteroplasmy Skeletal muscle Heart Eye Liver Kidney Pancreas Blood Inner Ear GI Tract Brain A single mitochondrial mutation may demonstrate heterogenous phenotypes!