Muscular weakness, wasting of muscles.

1. MUSCULAR DYSTROPHYMUSCULAR DYSTROPHY
Dr. Angelo Smith M.D
WHPL

2. • Causes
• Inheritance
• Dominant genes
• Recessive gene
Depends on the age when symptoms appear, and the
types of symptoms that develop.
• Risk
• Because these are inherited disorders, risk include a
family history of muscular dystrophy
How Many People Are Affected
It is estimated that between 50,000 -250,000 are
affected annually. 1 per 3500 live male births

4. • Muscular dystrophy is a heterogeneous
group of inherited disorders recognized
by progressive degenerative muscle
weakness and loss of muscle tissue
(started in childhood).
• Affect muscles strength and action.
• Generalized or localized.
• Skeletal muscle and other organs may
involve
• Limitation: Difficulties with walking or Maintaining posture,
Muscle spasms. Neurological, Behavioral, Cardiac, or other
Functional limitations.

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

11. Duchenne Muscular Dystrophy
Guillaume Benjamin Amand Duchenne
(French neurologist, 1860s)

12. • Etiology
▫ single gene defect
▫ Xp21.2 region
▫ absent dystrophin

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

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

16. 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 de
cade

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

20. Disappearance of
lordosis while sitting

21. DMD: Diagnosis
• Gait
• Absent DTR
• Ober test
• Thomas test
• Meyeron sign - child
slips through truncal
grasp
• Macroglossia
• Myocardial deterioration
• IQ ~ 80
• Increase CPK
(200x)
• Myopathic change in
EMG
Bx: m. degeneration
• Immunoblotting:
Absence dystrophin
• DNA mutation
analysis

26. Becker Muscular Dystrophy
Peter Emil Becker
(German doctor, 1950s)

27. • Milder version of
DMD
• Etiology
▫ single gene defect
▫ short arm X
chromosome
▫ altered size &
decreased amount
of dystrophin

29. • Less common
▫ 1: 30000 live male birth
• Less severe
• Family history: atypical MD
• Similar & less severe than DMD
• Onset: age > 7 years
• Pseudohypertrophy of calf
• Equinous and varus foot
• High rate of scoliosis
• Less frequent cardiac involvement
Clinical features

30. Diagnosis
• The same as DMD
• Increase CPK (<200x)
• Decrease dystrophin and/or altered size
Natural history
▫ Slower progression
▫ ambulate until adolescence
▫ longer life expectancy
Treatment
▫ the same as in DMD
▫ forefoot equinous: plantar release, midfoot dorsal-
wedge osteotomy

32. Emery-Dreifuss Muscular Dystrophy
• Etiology
▫ X-linked recessive
▫ Xq28
▫ Emerin protein (in
nuclear membrane)
• Epidemiology
▫ Male: typical phenotype
▫ Female carrier: partial
• Clinical Features
▫ Muscle weakness
▫ Contracture
 Neck extension,
elbow, achillis tendon

33. Scoliosis: common, low incidence of
progression
Bradycardia, 1st degree AV block  sudden
death

34. • 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.

35. 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

36. Limb - Girdle Muscular
Dystrophy
•Etiology
▫ Autosomal recessive at chromosome
15q
▫ Autosomal dominant at 5q
•Epidemiology
▫ Common
▫ More benign

38. • Clinical
manifestation
▫ Age of onset: 3rd
decade
▫ Initial:
pelvic/shoulder m.
(proximal to distal)
▫ Similar distribution
as DMD

39. Hemiatrophy

40. •Classification
▫ Pelvic girdle type
 common
▫ Scapulohumeral
type
 rare
• Diagnosis
▫ Same clinical as
DMD/BMD carriers
▫ Moderately elevated
CPK
▫ Normal dystrophin

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

42. Fascioscapulohumeral Muscular
Dystrophy
• Etiology
▫ Autosomal dominant
▫ Gene defect (FRG1)
▫ Chromosome 4q35
• Epidemiology
▫ Female > male
• Clinical
manifestation
▫ Age of onset: late
childhood/ early adult
▫ No cardiac, CNS
involvement
▫ Winging scapula
▫ Markedly decreased
shoulder flexion &
abduction
▫ Horizontal clavicles
▫ Rare scoliosis

44. • Muscle weakness
▫ face, shoulder, upper arm
• Sparing
▫ Deltoid
▫ Distal pectoralis major
▫ Erector spinae

45. • “Popeye”
appearance
▫ Lack of facial mobility
▫ Incomplete eye
closure
▫ Pouting lips
▫ Transverse smile
▫ Absence of eye and
forehead wrinkles
POPEYE ARMS

46. • Diagnosis
▫ PE, 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)

47. Distal Muscular Dystrophy
• Autosomal dominant trait
• Rare
• Dysferlin (mb prot) defect
• Age of onset: after 45 yrs
• Initial involvement:
intrinsic hands, claves,
tibialis posterior
• Spread proximally
• Normal sensation

49. Congenital Muscular
Dystrophy
• Etiology
▫ Autosomal recessive
▫ Integrin, fugutin defect
• Epidemiology
▫ Rare
▫ Both male and female
• Classification
▫ Merosin-negative
▫ Merosin-positive
▫ Neuronal migration
 Fukuyama
 Muscle eye-brain
 Wlaker-Warburg

50. Clinical manifestation
• Stiffness of joint
• Congenital hip
dislocation,
subluxation
• Achillis tendon
contracture, talipes
equinovarus
• Scoliosis

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

52. Oculopharyngeal Muscular
Dystrophy
• Autosomal dominant
• Age of onset: 3rd decade
• Ptosis in middle life
• Pharyngeal involvement
▫ Dysarthria
▫ Dysphasia
▫ Repetitive regurgitation
▫ Frequently choking

53. Myotonic Muscular Dystrophy
HATCHET FACIES

54. `Classical form' of the disease is seen in
adolescent or early adult life with variable
presenting features.
• Muscular weakness,
•myotonia,
•mental retardation,
•cataract,
•neonatal problems
•18% remain asymptomatic.

55. 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 -

56. 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 Hypertrophyt
achycardia
Very rare Very rare Very rare Not
observed
Intellectual decrease Normal Normal Normal ?
Course Stead, rapid Slow Insidious benign Steady

58. Treatment
is generally aimed at
controlling the onset of
symptoms to maximize the
quality of life.