Muscular Dystrophy : Duchenne and Becker's

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Muscular Dystrophy : Duchenne and Becker's

  1. 1. Neuromuscular Disorders –Duchenne and Becker’s Muscular Dystrophy Dr. Kalpana Malla MD Pediatrics Manipal Teaching HospitalDownload more documents and slide shows on The Medical Post [ www.themedicalpost.net ]
  2. 2. Neuromuscular disordersConsists 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. 3. May be• Genetic• Congenital• Acquired• Acute• Chronic• Progressive• Static
  4. 4. Myopathy• Proximal distribution of weakness and muscle wasting except- myotonic muscular dystrophy• Slow progression• Tendon reflexes – preserved• Sensation – intact
  5. 5. Neuropathy• Distal distribution (except- juvenile spinal muscular atrophy• Acute onset• Tendon reflexes – lost• Sensory abnormalities –neuropathy
  6. 6. Classification1. Muscular dystrophies: -X-linked recessive -Duchenne / becker Limb –girdle MD - Cong muscular dystrophies - Facioscapulohumeral - Oculopharyngeal - Myotonic dystrophy - Scapuloperoneal dystrophy
  7. 7. Classification2.Disorder of neuromuscular junction - Myesthenia gravis3.Myotonic syndromes4. Myopathies a ) Congenital myopathies b ) Endocrine - Hypothyroidism - Hyperparathyroidism
  8. 8. Classificationb ) Endocrine - Steroid-induced - HyperaldosteronismC ) Metabolic – K-related periodic paralysis - Mitochondrial disorders
  9. 9. Classification5. Inflammatory myopathies (myasthitis):A. Idiopathic – Juvenile dermatomyositis - polymyositisB. Infectious – viral, parasitic, bacterial, fungal6. Floppy infant syndrome
  10. 10. EvaluationClinical –• Muscle – bulk, tone ,power,• Head lag• See involvement of face, tongue, palate ,extra- ocular muscles• Fasciculations – sign of denervation
  11. 11. Evaluation• Undescended testes, funnel shaped thorax - congenital NMD• Generalized hypotonia, delayed motor development
  12. 12. Laboratory findings• Serum enzymes – CPK• Nerve conduction velocity- motor & sensory conduction measured electrophysiologically• Electromyelography - records maximum voluntary contraction of muscle
  13. 13. Laboratory findings• Muscle biopsy – most important, specific and diagnostic (Vastus lateralis)• Nerve biopsy (sural nerve)• ECG-cardiac evaluation in myopathies
  14. 14. Duchenne muscular dystrophy
  15. 15. 16
  16. 16. 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
  17. 17. Duchenne Muscular Dystrophy• Commonest muscular dystrophy• Incidence- 1/3600 male birth• Inheritance – X- linked recessive 30% - new mutations sporadic 18
  18. 18. 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
  19. 19. X-Linked recessiveFeatures-1.Only males are affected. All his daughters will be carriers as they receive abnormal X from father2. Will not manifest in females- 50% sons affected 50% daughters will be carriers when the mother is a carrier 20
  20. 20. 21
  21. 21. 22
  22. 22. X-Linked recessive3.Normal sons do not transmit disease4.Pattern of inheritance is oblique as only males on the maternal side are affected5.Females may be affected when affected male marries a carrier female/or when only one X chromosome is present 23
  23. 23. 24
  24. 24. X-Linked recessive6. Fresh mutations are known7. Carriers may have biochemical abnormalities 25
  25. 25. • 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
  26. 26. 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
  27. 27. 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
  28. 28. 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
  29. 29. • 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
  30. 30. Gets up climbing up his legs- Gower’s sign
  31. 31. • Enlargement of the calves (pseudohypertrophy) and wasting of thigh muscles is a classic feature.• Next most common site of muscular hypertrophy - tongue, forearm.
  32. 32. • 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.
  33. 33. • Pseudohypertrophy seen in supra, infraspinatus, deltoids – Valley sign 34
  34. 34. 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
  35. 35. 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
  36. 36. 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
  37. 37. 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.
  38. 38. • 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
  39. 39. • 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
  40. 40. 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
  41. 41. EMG• Electromyography (EMG) shows characteristic myopathic features but is not specific for Duchenne muscular dystrophy• Nerve conduction velocity- normal, No evidence of denervation
  42. 42. Muscle biopsy –• Diagnostic (Vastus lateralis/ Gastrocnemius)Myopathic changes –• endomysial connective tissue proliferation• Scattered degenerating and regenerating myofibers• Foci of mononuclear inflammatory cell infiltrates
  43. 43. Muscle biopsy 45
  44. 44. 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
  45. 45. • Molecular genetic diagnosis - demonstrating deficient or defective dystrophin by immunohistochemical staining of sections of muscle biopsy
  46. 46. 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
  47. 47. ManagementMultidisciplinary approach:• Exercise – physical exercise, physiotherapy• Dietary – prevent obesity• Orthopedic• Psychological• Education• Genetic counselling 49
  48. 48. • Physiotherapy delays but does not always prevent contractures.
  49. 49. • 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
  50. 50. 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
  51. 51. 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
  52. 52. 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
  53. 53. To improve breathing:• Pulmonary infections should be promptly treated.• O2 therapy• Ventilator• Scoliosis surgery• Tracheotomy
  54. 54. • Cardiac decompensation often responds well to digoxin, at least in early stages.• Immunizations for influenza virus and routine vaccinations are indicated.
  55. 55. 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.
  56. 56. 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
  57. 57. DermatomyositisPathognomonic feature -Gottronspapules overlying the dorsalinterphalangeal joints.
  58. 58. Gottrons sign: Erythematous or violaceous atrophic macules and plaques overlying the dorsal interphalangeal joints and sparing the interphalangeal spaces
  59. 59. HeliotropeCharacteristic finding a violaceous eruption with periorbital edema.
  60. 60. Shawl sign. Poikilodermatous macules appear in a "shawl" distribution over the shoulder, arms and upper back
  61. 61. Mechanics hand.Fissured, scaly, hyperkeratotic and hyperpigmented hands are suggestive of manual labor
  62. 62. Thank youDownload more documents and slide shows on The Medical Post [ www.themedicalpost.net ]

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