1. Muscular Dystrophies Patarawan Woratanarat, MD, PhD Department of Orthopaedics Faculty of Medicine Ramathibodi Hospital

2. A 7-year-old boy presents with progressive weakness of both legs for 4 years.

6. Definition A group of noninflammation inherited distroders
progressive degeneration and weakness of skeletal muscles
without cause in peripheral / central nervous system

7. Classification Sex-linked: DMD, BMD, EDMD
Autosomal recessive: LGMD, infantile FSHD
Autosomal dominant: FSHD, distalMD, ocular MD, oculopharyngeal MD.

8. Duchenne Muscular dystrophy
Guillaume Benjamin Amand Duchenne
(French neurologist, 1860s)

9. Duchenne Muscular dystrophy
Etiology
single gene defect
Xp21.2 region
absent dystrophin

10. Duchenne Muscular dystrophy

11. Duchenne Muscular dystrophy

12. DMD: pathology

13. DMD: Epidemiology Most common male, Turner syndrome
1:3500 live male birth
1/3 new mutation
65% family history

14. DMD: Clinical manifestation
Onset : age 3-6 years
Progressive weakness
Pseudohypertrophy of calf muscles
Spinal deformity
Cardiopulmonary involvement
Mild - moderate MR

15. Pseudohypertrhophy of calf muscle, Tip toe gait
forward tilt of pelvis, compensatory lordosis

16. Disappearance of lordosis while sitting

17. DMD: Diagnosis
Gower’s sign

18. DMD: Diagnosis Increase CPK (200x) Gait
Myopathic change in EMG Bx: m. degeneration
Immunoblotting: Absence dystrophin
DNA mutation analysis
Gait
absent DTR
Ober test
Thomas test
Meyeron sign
Macroglossia
Myocardial deterioration
IQ ~ 80

19. Western blot
Normal dystrophin bands (230kD)

21. DMD: Natural history Progress slowly and continuously muscle weakness
lower --> upper extremities
unable to ambulate: 10 year (7-12)
death from pulmonary/ cardiac failure: 2-3rd decade

22. DMD: Treatment Prednisolone Dystrophin replacement Maintain function
PMR
orthosis
cardiopulmonary Rx
Counselling

24. DMD: Treatment Surgery
Foot & ankle: Achillis, Tibialis posterior release
Knee: Yount, hamstring release
Hip: Ober, modified Soutter procedure

25. DMD: Treatment An 8-yr-old boy Unable to stand Percut. Tenotomy
Achillis tendon
Ambulate with
orthosis

26. DMD: Treatment Surgery Upper extremity: -
Spinal deformity: posterior spinal fusion + pelvis

27. Becker muscular dystrophy
Peter Emil Becker
(German doctor, 1950s)

28. Becker muscular dystrophy
Milder version of DMD
Etiology
single gene defect
short arm X chromosome
altered size & decreased amount of dystrophin

29. Becker muscular dystrophy

30. BMD: Epidemiology Less common Less severe Family history: atypical MD
1: live male birth
Less severe
Family history: atypical MD

31. BMD: Clinical manifestation
Similar & less severe than DMD
Onset: age > 7 years
Pseudohypertrophy of calf
Equinous and varus foot
High rate of scoliosis
Less frequent cardiac involvement

32. BMD: Diagnosis The same as DMD Increase CPK (<200x)
Decrease dystrophin and/or altered size

33. BMD Natural history Treatment Slower progression
ambulate until adolescence
longer life expectancy
Treatment
the same as in DMD
forefoot equinous: plantar release, midfoot dorsal-wedge osteotomy

34. Emery-Dreifuss muscular dystrophy
Etiology
X-linked recessive
Xq28
Emerin protein (in neuclear membrane)
Epidemiology
Male: typical phenotype
Female carrier: partial

35. EDMD: Clinical manifestation
Muscle weakness
Contracture
Neck extension, elbow, achillis tendon

36. EDMD: Clinical manifestation
Scoliosis: common, low incidence of progression
Bradycardia, 1st degree AV block  sudden death

37. EDMD Natural history Diagnosis 1st 10 y: mild weakness Gower’s sign
Later: contracture, cardiac abnormality
5th-6th decade: can ambulate
Poor prognosis in obesity, untreated equinus contractures.
Diagnosis
Gower’s sign
Mildly/moderately elevated CPK
EMG: myopathic
Normal dystrophin

38. EDMD: Treatment Physical therapy Soft tissue contracture
Prevent contracture: neck, elbow, paravertebral muscles
For slow progress elbow flexion contracture
Soft tissue contracture
Achillis lengthening, posterior ankle capsulotomy + anterior transfer of tibialis posterior
Spinal stabilization
For curve > 40 degrees
Cardiologic intervention
Cardiac pacemaker

39. Limb-girdle muscular dystrophy
Eitology
Autosomal recessive at chromosome 15q
Autosomal dominant at 5q
Epidemiology
Common
More benign

40. Limb-girdle muscular dystrophy
an absence of functional sarcoglycans components of the dystrophin glycoprotein complex (DCG).
Other LGMD result from the absence of functional caveolin-3

41. Limb-girdle muscular dystrophy
Clinical manifestation
Age of onset: 3rd decade
Initial: pelvic/shoulder m. (proximal to distal)
Similar distribution as DMD

42. LGMD Diagnosis Classification Same clinical as DMD/BMD carriers
Pelvic girdle type
common
Scapulohumeral type
rare
Diagnosis
Same clinical as DMD/BMD carriers
Moderately elevated CPK
Normal dystrophin

43. LGMD Natural history Treatment Slow progression Similar to DMD
After onset > 20 y: contracture & disability
Rarely significant scoliosis
Treatment
Similar to DMD
Scoliosis: mild, no Rx.

44. Fascioscapulohumeral muscular dystrophy
Etilogy
Autosomal dominant
Gene defect (FRG1)
Chromosome 4q35
Epidemiology
Female > male
Clinical manifestation
Age of onset: late childhood/ early adult
No cardiac, CNS involvement

45. FSMD: Clinical manifestation
Muscle weakness
face, shoulder, upper arm
Sparing
Deltoid
Distal pectoralis major
Erector spinae

46. “Popeye” appearance Lack of facial mobility Incomplete eye closure
Pouting lips
Transverse smile
Absence of eye and forehead wrinkles

47. FSMD: Clinical manifestation
Winging scapula
Markedly decreased shoulder flexion & abduction
Horizontal clavicles
forward sloping
Rare scoliosis

48. FSMD Treatment Diagnosis Natural history
Posterior scpulocostal fusion/ stabilization (scapuloplexy)
Diagnosis
PE, muscle biopsy
Normal serum CPK
Natural history
Slow progression
Face, shoulder m.  pelvic girdle, tibialis ant
Good life expectancy

49. Distal muscular dystrophy
Autosomal dominant trait
Rare
Dysferlin (mb prot) defect
Age of onset: after 45 y

50. Distal muscular dystrophy
Initial involvement: intrinsic hands, claves, tibialis posterior
Spread proximally
Normal sensation

51. DD: Classification Welander distal myopathy
Finnish/Markesbery distal myopathy
Miyoshi distal myopathy
Nonaka distal myopathy
Gower: autosomal dominant, Chromosome 14
Hereditary inclusion-body myositis
Hereditary inclusion-body myuositis
Distal myopathy with vocal cord & pharyngeal weakness

52. Congenital muscular dystrophy
Etiology
Autosomal recessive
Integrin, fugutin defect
Laminin 2 chain
merosin

53. CMD: Epidemiology Classification Rare Both male and female
Merosin-negative
Merosin-positive
Neuronal migration
Fukuyama
Muscle eye-brain
Wlaker-Warburg

54. CMD: Clinical manifestation
Stiffness of joint
Congenital hip dislocation, subluxation
Achillis tendon contracture, talipes equinovarus
Scoliosis

55. CMD Diagnosis Treatment Muscle Bx: Perimysial and endomysial fibrosis
Physical therapy
Orthosis
Soft tissue release
Osteotomy

56. Summary Clinical DMD LGMD FSMD DD CMD Incidence common less Not common
Rare
Age of onset
3-6 y
2nd decade
20-77 y
At/ after birth
Sex
Male
Either sex
M = F
Both
Inheritance
Sex-linked recessive
AR, rare AD AD
Unknown
Muscle involve.
Proximal to distal
Face & shoulder to pelvic
Distal
Generalized
Muscle spread until late
Leg, hand, arm, face, larynx,eye
Upper ex, calf
Back ext, hip abd, quad
Proximal -

57. Summary Clinical DMD LGMD FSMD DD CMD Pseudo hypertrophy 80% calf
< 33%
Rare no No
Contracture
Common
Late
Mild, late
Severe
Scoliosis
Kyphoscoliosis
Common, late - ?
Heart
Hypertrophytachycardia
Very rare
Not observed
Intellectual
decrease
Normal
Course
Stead, rapid
Slow
Insidious
benign
Steady

58. Thank you

59. Infantile fascioscapulohumeral muscular dystrophy
Clinical manifestation
Facial diplegia
Sensorinueral hearing loss
Mobius type of facial weakness
Walk with hands and forearms folded across upper buttocks
**Marked & progressive lumbar lordosis (pathog)
Less common equinous, scoliosis
Etiology
Autosomal recessive
Unidentified gene

60. IFSMD Natural history Treatment Infancy: facial diplegia
Childhood: sensorineural hearing loss
2nd decade of life: wheelchair bound, severely compromised pulmonary function
Treatment
Flexible equinous/equinovarus foot: AFO + TAL
Hip flextion contracture: no Rx in ambulate pt.
Spinal deformity in wheelchai ambulator: orthosis+ post spinal fusion with instrumentation
Scapulothoracic stabilization: not necessary

61. Ocular muscular dystrophy
Rare
Age of onset: adolescence
Extraocular muscle weakness  diplopia  limit ocular movement
May involve proximal upper extremities
Slowly progressive

62. Oculopharyngeal muscular dystrophy
Autosomal dominant with complete penetrane
Age of onset: 3rd decade
Ptosis in middle life

63. OPMD Pharyngeal involvement Dysarthria Dysphasia
Repetitive regurgitation
Frequently choking