1. Neuromuscular Disorders –
Duchenne and Becker’s Muscular
Dystrophy
Dr. Kalpana Malla
MD Pediatrics
Manipal Teaching Hospital
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2. Neuromuscular disorders
Consists of - Motor neuron in brain stem
- Ventral horn of spinal cord
- Its axon with other axon forms
peripheral nerve
- Neuromuscular junction
- All muscle fibers innervated by
single motor neuron

3. May be
• Genetic
• Congenital
• Acquired
• Acute
• Chronic
• Progressive
• Static

4. Myopathy
• Proximal distribution of weakness and muscle
wasting except- myotonic muscular dystrophy
• Slow progression
• Tendon reflexes – preserved
• Sensation – intact

5. Neuropathy
• Distal distribution (except- juvenile spinal
muscular atrophy
• Acute onset
• Tendon reflexes – lost
• Sensory abnormalities –neuropathy

6. Classification
1. Muscular dystrophies:
-X-linked recessive -Duchenne / becker
Limb –girdle MD
- Cong muscular dystrophies
- Facioscapulohumeral
- Oculopharyngeal
- Myotonic dystrophy
- Scapuloperoneal dystrophy

7. Classification
2.Disorder of neuromuscular junction
- Myesthenia gravis
3.Myotonic syndromes
4. Myopathies
a ) Congenital myopathies
b ) Endocrine
- Hypothyroidism
- Hyperparathyroidism

8. Classification
b ) Endocrine - Steroid-induced
- Hyperaldosteronism
C ) Metabolic – K-related periodic paralysis
- Mitochondrial disorders

9. Classification
5. Inflammatory myopathies (myasthitis):
A. Idiopathic – Juvenile dermatomyositis
- polymyositis
B. Infectious – viral, parasitic, bacterial, fungal
6. Floppy infant syndrome

10. Evaluation
Clinical –
• Muscle – bulk, tone ,power,
• Head lag
• See involvement of face, tongue, palate ,extra-
ocular muscles
• Fasciculations – sign of denervation

11. Evaluation
• Undescended testes, funnel shaped thorax -
congenital NMD
• Generalized hypotonia, delayed motor
development

12. Laboratory findings
• Serum enzymes – CPK
• Nerve conduction velocity- motor & sensory
conduction measured electrophysiologically
• Electromyelography - records maximum
voluntary contraction of muscle

13. Laboratory findings
• Muscle biopsy – most important, specific and
diagnostic (Vastus lateralis)
• Nerve biopsy (sural nerve)
• ECG-cardiac evaluation in myopathies

14. Duchenne muscular
dystrophy

16. 16

17. What is Duchenne Muscular Dystrophy?
• The disease characterized by:
- Early onset often before school age
- Progressive muscular deterioration and
death by 14 - 18 years of age
- Defect on a large gene on X chromosome
17

18. Duchenne Muscular Dystrophy
• Commonest muscular dystrophy
• Incidence- 1/3600 male birth
• Inheritance – X- linked recessive
30% - new mutations
sporadic
18

19. FACTS
• The abnormal gene is on the X chromosome at the
Xp21 locus
• Becker muscular dystrophy is the same
fundamental disease as Duchenne dystrophy, with a
genetic defect at the same locus, but clinically it
follows a milder and more protracted course

20. X-Linked recessive
Features-
1.Only males are affected. All his daughters will be
carriers as they receive abnormal X from father
2. Will not manifest in females- 50% sons affected
50% daughters will be carriers when the mother is a
carrier
20

21. 21

22. 22

23. X-Linked recessive
3.Normal sons do not transmit disease
4.Pattern of inheritance is oblique as only males
on the maternal side are affected
5.Females may be affected when affected male
marries a carrier female/or when only one X
chromosome is present
23

24. 24

25. X-Linked recessive
6. Fresh mutations are known
7. Carriers may have biochemical
abnormalities
25

26. • A muscular dystrophy is distinguished from all
other neuromuscular diseases by four obligatory
criteria:
(1) It is a primary myopathy
(2) It has a genetic basis
(3) The course is progressive
(4) Degeneration and death of muscle fibers occur
at some stage in the disease

27. DMD - Muscle wasting
• In DMD - attachment of muscle fibers to their surrounding
endomysium (extracellular matrix) becomes weakened due
to mutations in the dystrophin gene.
• The absence of dystrophin leads to increased death and
destruction
• In turn, scar tissue (a mix of collagen and blood vessels)
replaces the muscle fibers, and it can gradually contract
leading to increased muscle rigidity

28. Clinical features
• Asymptomatic at birth - Early gross motor skills (
rolling over, sitting, standing) may be normal or
mildly delayed
• Poor head control in infancy may be the first sign
of weakness
• Walking achieved at the normal age - but hip girdle
weakness may be seen in subtle form as early as
the 2nd year - waddling gait

29. Clinical features
• Weakness starts in pelvic girdle- Extensor
muscles of back affected – lordosis to stabilize
spine by bony opposition
• Toddlers may assume a lordotic posture when
standing to compensate for gluteal weakness.
• Cannot bend forward without falling

30. • Presents – 2- 4 yrs
• Frequently falls, has difficulty getting up,
climbing stairs or getting in and out of a car
• An early Gower’s sign is often evident by age 3
yr and is fully expressed by age 5 or 6 yr

31. Gets up climbing up his legs- Gower’s sign

32. • Enlargement of the calves
(pseudohypertrophy) and wasting of thigh
muscles is a classic feature.
• Next most common site of muscular
hypertrophy - tongue, forearm.

33. • Pseudohypertrophy also seen - triceps,
quadriceps
• Pseuhypertrophy of muscle fibers - infiltration
of muscle by fat, and proliferation of collagen.
• Fasciculations of the tongue do not occur.

34. • Pseudohypertrophy seen in
supra, infraspinatus, deltoids
– Valley sign
34

35. Clinical features
• Hypertrophy of calf muscles with
tightening of tendo achillis-toe walking
• By 8 yrs –walking becomes difficult
• Knee jerks disappear early but ankle jerk may be
preserved
• Positive valley sign

36. Clinical features cont.
• By 12 yrs – wheel chair bound –
• Loss of lordosis - lose stabilization of spine
↓
Tendency to tilt to one side
↓
Develop– Scoliosis
↓
Bunching of ribs leads to E. reflux with acute
esophagitis, hematemesis, aspiration
pneumonitis 36

37. Clinical features cont.
• Intellectual impairment in all
• 20- 30% - IQ < 70
• Cardiac muscle may be affected –
Cardiomyopathy
• Die by 18 yrs – respiratory failure, pneumonia,
aspiration, heart failure
37

38. Clinical features
• By 12 yrs –wheel chair bound – loss of lordosis
lose stabilization of spine – tendency to tilt to
one side - develop –scoliosis-bunching of ribs
leads to E. reflux with acute esophagitis,
hematemesis, aspiration pneumonitis
• Contractures most often involve the ankles,
knees, hips, and elbows.
• Scoliosis is common.

40. • The function of distal muscles is usually well
preserved - child can continue using eating
utensils, a pencil, and a computer keyboard.
• Respiratory muscle involvement - weak and
ineffective cough, frequent pulmonary infections
• Pharyngeal weakness - episodes of
aspiration, nasal regurgitation of liquids, and an
airy or nasal voice quality
• Extraocular muscles - well preserved

41. • Death occurs usually at about 18 yr of age.
• The causes of death are respiratory failure in sleep,
intractable heart failure, pneumonia, or
occasionally aspiration and airway obstruction

42. Laboratory findings
• Serum creatinine phosphokinase (CPK)  even in
presymptomatic stages, including at birth
> 10,000 units ( range 15,000 – 35,000 IU/L)
Normal level < 160 IU/L
- In severe cases, maybe lower
• Other lysosomal enzymes of muscles:
Aldolase, Aspartate aminotransferase –
increased (less specific)
42

43. EMG
• Electromyography (EMG) shows characteristic
myopathic features but is not specific for Duchenne
muscular dystrophy
• Nerve conduction velocity- normal, No evidence of
denervation

44. Muscle biopsy –
• Diagnostic (Vastus lateralis/ Gastrocnemius)
Myopathic changes –
• endomysial connective tissue proliferation
• Scattered degenerating and regenerating myofibers
• Foci of mononuclear inflammatory cell infiltrates

45. Muscle biopsy
45

46. Others
• Cardiac evaluation
• CXR
• ECG
• ECHO
• Molecular genetic diagnosis –
Immunohistochemical staining of section of
muscle biopsy or by DNA analysis from
peripheral blood -- absent dystrophin
46

47. • Molecular genetic diagnosis - demonstrating
deficient or defective dystrophin by
immunohistochemical staining of sections of
muscle biopsy

48. Treatment
• No medical cure or a method of slowing its
progression.
• To improve mobility:
– Physical therapy
– Surgery on tight joints
– Prednisone
– Non-steroidal medications
– Wheelchair

49. Management
Multidisciplinary approach:
• Exercise – physical exercise, physiotherapy
• Dietary – prevent obesity
• Orthopedic
• Psychological
• Education
• Genetic counselling
49

50. • Physiotherapy delays but does not always
prevent contractures.

51. • Preservation of a good nutritional state
• Adequate calcium intake - to minimize
osteoporosis
• sedentary children burn fewer calories than active
children and depression is an additional factor –
these children tend to eat excessively and gain
weight – Obesity makes a patient with myopathy
even less functional

52. Management
• Pharmacological-treat complication
• Suggestion – To reduuce rate of deterioration
cyclical ( 10 days /month)-catabolic steroid –
prednisolone low dose -decreases the rate of
apoptosis and may decelerate the myofiber
necrosis
• Cyclosporin – under study

53. Some approaches
• Experimental approach – Myoblast transfer
therapy
• Unproven approach – I/M injection of
recombinant dystrophin gene
• "minigenes," which carry instructions for a
slightly smaller version of dystrophin
53

54. Advances in Gene Therapy
• Researchers - created the so-called gutted
virus, a virus that has its own genes removed
so that it is carrying only the dystrophin gene

55. To improve breathing:
• Pulmonary infections should be promptly
treated.
• O2 therapy
• Ventilator
• Scoliosis surgery
• Tracheotomy

56. • Cardiac decompensation often responds well to
digoxin, at least in early stages.
• Immunizations for influenza virus and routine
vaccinations are indicated.

57. GENETIC COUNCELLING
• Prenatal diagnosis for women having risk
pregnancies - with a family history of muscular
dystrophy.
• Identification of dystrophin gene exon deletions
in a male fetus - Couples may elect to terminate
the pregnancy if the fetus is affected.
• Carrier status may be determined in the mother
and siblings of the proband.

58. Becker muscular dystrophy
• This Ds was first described by Becker and Klener in
1955
• X-linked recessive
• Late onset – ambulatory till late adolescence
• Calf pseudohypertrophy, cardiomyopathy, increased
CPK are similar to DMD
• Learning disabilities are less
• Death – in late 20s but severely disabled; fewer than
half of patients are still alive by age 40 yr

59. Dermatomyositis
Pathognomonic feature -Gottron's
papules overlying the dorsal
interphalangeal joints.

60. Gottron's sign:
Erythematous or
violaceous atrophic
macules and
plaques overlying
the dorsal
interphalangeal
joints and sparing
the interphalangeal
spaces

61. Heliotrope
Characteristic finding a violaceous
eruption with periorbital edema.

62. Shawl sign. Poikilodermatous macules appear in a
"shawl" distribution over the shoulder, arms and
upper back

63. Mechanic's hand.
Fissured, scaly, hyperkeratotic and
hyperpigmented hands are suggestive of
manual labor

64. Thank you
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Medical Post [ www.themedicalpost.net ]