Muscular dystrophy

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 sexBoth
InheritanceSex-linked
recessive
AR, rare ADAD 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 rareVery 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.