Education

1. Muscular
Dystrophies

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

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

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

7. CLASSIFICATION
WALTON and NATTRASS
(1954)
1) Duchenne type and BMD
2) Emery Dreifuss
3) Limb girdle
4) Facioscapulohumeral
5) Distal
6) Occulopharyngeal BMJ 1998;317
4 5 6
1
2 3

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

9. DUCHENNE MUSCULAR
DYSTROPHY:
 First described in 1881- dystrophin gene
discovered in the early 1980's
 Cause: deficiency of dystrophin, resulting in
progressive loss of muscle fibers
 X-chromosome linked
 Asymptomatic carrier
 1 in 3500 live births, occurs in boys, girls are
carriers.
MUSCULAR DYSTROPHY 9

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

11. MUSCULAR DYSTROPHY 11

12. Duchenne Muscular dystrophy

13. Duchenne Muscular dystrophy

14. MUSCULAR DYSTROPHY 14

15. DMD: pathology

16. DMD: Epidemiology
 Most common in male
 1:3500 live male birth
 1/3 new mutation
 65% family history

17. DUCHENNE MUSCULAR DYSTROPHY
Commonest muscular dystrophy
Incidence 1 in 3500 live births
Prevalence 3 in one lakh
X-Linked recessive
Predominantly affects boys
Presents with proximal
muscleweakness

18. DMD: Clinical manifestation
 Onset : age 3-6 years
 Progressive weakness
 Pseudohypertrophy of
calf muscles
 Spinal deformity
 Cardiopulmonary
involvement

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

20. Disappearance of lordosis while sitting

21. DMD: Diagnosis
Gower’s sign

22. Gowers' sign

23. Symptoms start by 3 yrs age
Weakness : proximal more than
distal,symmetric
Muscles involved Add.magnus, tendoachilis,
quadriceps shoulders girdles
Course : reduced motor function by 2-3
years

24. CONTRACTURES: Hips, Knees.
SCOLIOSIS: Occurs after loss of ambulation.
CARDIOMYOPATHY: Dilated.After 15 yrs. Age.
MENTAL RETARDATION: 1/3rd have slow
mentation.10-20% have IQ of less than 70.
NIGHT BLINDNESS: Dystrophin in outer
plexiform layer is involved.
MUSCULOSKELETAL:

25. MUSCULAR HYPERTROPHY:
Predominantly seen in calf muscles.
Increases with age.
Muscle fibrosis and fat.
Relatively spared muscles have pseudohypertrophy.

26. Shows ‘a valley between the two mounts’ behind each
shoulder. The infraspinatus and deltoid muscles (arrow
heads) are enlarged like two mounts and in between
them, all
the muscles forming the posterior axillary fold are
wasted
forming an oval valley (arrrow).
VALLEY’S (or) PRADHAN SIGN (or)
POLY HILL’S SIGN

27. DMD: Diagnosis
 Gait
 Ober test
 Thomas test
 shoulder abdction
range is decreased
 Macroglossia- large
tongue
 IQ ~ 80
 Increase CPK (200x)-
creatine phosphokinase
 Myopathic change in
EMG
Bx: m. degeneration
 Immunoblotting: Absence
dystrophin
 DNA mutation analysis

29. EMG
Differentiate neuropathy and
myopathy.
Low amplitude,polyphasic action
potentials,
with early interference pattern.

30. MUSCLE BIOPSY IN DMD:
• Lack of immunostaining of dystrophin in muscle biopsy
specimen
• Demonstration of deletion in the dystrophin gene
MUSCULAR DYSTROPHY 30
Normal Duchene dystrophy

31. GENETIC ANALYSIS:
Dystrophin gene analysis by PCR technique,
using
WBC from peripheral blood or muscle specimen.

32. 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

33. DMD: Treatment
 Dystrophin replacement
 Maintain function
 orthosis
 cardiopulmonary Rx
 Counselling

34. Physical treatment :
passive stretching, orthopedic appliances
wheelchairs and braces.
Surgical treatment:
Fasciotomies, tendon lengthening.

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

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

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

39. COMPLICATIONS:
Deformities,decreased mobility
Pneumonia and respiratory infections.
Respiratory failure.
Cardiomyopathy.
Congestive heart failure.
cardiac arrhythmias.

40. Duchenne muscular dystrophy rapidly
progressive.
Death usually occurs by age 25.
Typically from respiratory or cardiac failure.
Mechanical ventilation and steroids have
increased
life span.
PROGNOSIS:

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

42. BECKER MUSCULAR DYSTROPHY
BECKER and KEINER described
in1955.
Other end of the spectrum of DMD.
Dystrophin is reduced in
quantity/quality.
Clinical features are same but mild and
late.

43. Age of onset 12yrs.
By 25yrs.unable to walk.
Death in 5th decade.
BMD Cont,

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

45. Becker muscular dystrophy

46. BMD: Epidemiology
 Less common
 1: 30000 live male birth
 Less severe
 Family history: atypical MD

47. 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

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

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

50. DIFFERENCES B/W DMD &
BMD
 Dystrophin absent
 Frameshift mutation
 1/3rd new mutations
 Onset 2-4yr
 Loss of ambulation
10yrs
 Death by 20 yr
 Cardiomyopathy
common
 Dystrophin partially
present
 In-frame mutations
 New mutations rare
 Onset 12 yr
 Non ambulant 25-
30yrs
 5th decade
 Less common

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

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

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

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

55. EDMD: Treatment
 Physical therapy
 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

56. Limb-girdle muscular dystrophy
 Eitology
 Autosomal recessive at chromosome 15q
 Autosomal dominant at 5q
 Epidemiology
 Common

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

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

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

60. 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

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

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

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

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

65. Distal muscular dystrophy
 Autosomal dominant
trait
 Rare
 Age of onset: after 45 y

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

67. Congenital muscular dystrophy
 Etiology
 Autosomal recessive
Laminin 2 chain
merosin

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

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

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

71. Infantile fascioscapulohumeral
muscular dystrophy
 Etiology
 Autosomal recessive
 Unidentified gene
 Clinical manifestation
 Facial diplegia
 hearing loss
 facial weakness
 Walk with hands and
forearms folded across
upper buttocks
 **Marked & progressive
lumbar lordosis
 Less common equinous,
scoliosis

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

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

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

75. OPMD
 Pharyngeal
involvement
 Dysarthria
 Dysphasia
 Repetitive
regurgitation
 Frequently choking

76. Summary
Clinical DMD LGMD FSMD DD CMD
Incidence common less Not
common
Rare Rare
Age of onset 3-6 y 2nd decade 2nd decade 20-77 y At/ after
birth
Sex Male Either sex M = F Either sex Both
Inheritance Sex-linked
recessive
AR, rare AD AD AD Unknown
Muscle
involve.
Proximal to
distal
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 -

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

78. Thank you