Updated: 8/6/2018

Duchenne and Becker Muscular Dystrophy

Topic
Review Topic
0
0
Questions
2
0
0
Evidence
2
0
0
Videos
1
Overview
 

Snapshot
  • A 4-year-old boy is brought to his pediatrician by his mother for muscle weakness. She reports that he has trouble running with his friends and climbing the stairs. She also states that the patient has increased difficulty arising from a seated position on the ground and walks in a "waddling" way. On physical exam, there is significant proximal muscle weakness and pseudohypertrophy of the bilateral calves. He also has Gower sign. Laboratory testing is notable for a significantly elevated creatine kinase and aldolase. A sample is obtained for genetic analysis of the dystrophin gene. (Duchenne muscular dystrophy)
Introduction 
  • Clinical definition
    • inherited disorder of skeletal muscle leading to progressive muscle weakness
  • Epidemiology
    • incidence
      • Duchenne muscular dystrophy
        • most common early onset form
      • Becker muscular dystrophy
        • a relatively common form that typically presents later in life
    • demographics
      • male children
        • recall that males have only one X chromosome
  • Etiology
    • X-linked recessive mutation in the dystrophin gene 
      • Duchenne muscular dystrophy
        • frameshift or deletion of the dystrophin gene
          • results in complete loss of dystrophin
      • Becker muscular dystrophy
        • non-frameshift 
          • results in partial function of dystrophin
          • in other words, the reading frame is not disrupted
  • Pathogenesis
    • normal biology
      • dystrophin is one of the largest human genes and appears to be involved in
        • preventing muscle fiber degeneration by providing mechanical stability between the myofiber and its cell membrane 
          • connecting actin to α- and β-dystroglycan transmembrane proteins
        • cell signaling
      • dystrophin is expressed in cardiac, skeletal, and neural tissue
    • pathology
      • absent or decreased function of dystrophin leads to cycles of muscle fiber degeneration and regeneration
        • this subsequently leads to fatty replacement and a distorted fascicular architecture
  • Prognosis
    • Duchenne muscular dystrophy
      • mean age of death is 25-30 years of age and death results from
        • heart failure
        • respiratory failure
    • Becker muscular dystrophy
      • less severe than Duchenne muscular dystrophy
Presentation
  • Symptoms
    • progressive muscle weakness
      • most severe in the proximal muscles and lower extremity
    • waddling gait
  • Physical exam
    • Gower sign
      • a patient using their upper extremity to stand
        • signifies weakness of the proximal lower extremity muscles
    • calf pseudohypertrophy
    • lumbar lordosis
    • hypo- or areflexia
Studies
  • Labs
    • ↑ serum creatine kinase
    • ↑ aldolase, alanine transaminase, and aspartate transaminase
  • Genetic testing
    • confirms the diagnosis
  • Dystrophin analysis
    • Duchenne muscular dystrophy
      • complete or almost complete loss of dystrophin
    • Becker muscular dystrophy
      • dystrophin with abnormal molecular weight
      • reduced quantity of dystrophin
  • Biopsy
    • muscle fibril degeneration, regeneration, and isolated fiber hypertrophy
    • muscle replacement with fat and connective tissue
    • performed if genetic testing is negative
Differential
  • Limb-girdle muscular dystrophy
  • Spinal muscular atrophy
Treatment
  • Management approach
    • treatment for both Duchenne and Becker muscular dystrophy is multidisciplinary to manage symptoms and complications
  • Medical
    • glucocorticosteroids
      • indication
        • mainstay of treatment for patients with Duchenne muscular dystrophy
      • drugs
        • prednisone
        • deflazacort
      • adverse effects
        • weight gain
        • hirsutism
        • cushingoid appearance
Complications
  • Muscular
    • wheel chair bound
  • Cardiac
    • dilated cardiomyopathy
    • arrhythmia
  • Orthopedic
    • fractures secondary to falling
 
 

Please rate topic.

Average 4.5 of 2 Ratings

Thank you for rating! Please vote below and help us build the most advanced adaptive learning platform in medicine

The complexity of this topic is appropriate for?
How important is this topic for board examinations?
How important is this topic for clinical practice?
Questions (2)
Lab Values
Blood, Plasma, Serum Reference Range
ALT 8-20 U/L
Amylase, serum 25-125 U/L
AST 8-20 U/L
Bilirubin, serum (adult) Total // Direct 0.1-1.0 mg/dL // 0.0-0.3 mg/dL
Calcium, serum (Ca2+) 8.4-10.2 mg/dL
Cholesterol, serum Rec: < 200 mg/dL
Cortisol, serum 0800 h: 5-23 μg/dL //1600 h:
3-15 μg/dL
2000 h: ≤ 50% of 0800 h
Creatine kinase, serum Male: 25-90 U/L
Female: 10-70 U/L
Creatinine, serum 0.6-1.2 mg/dL
Electrolytes, serum  
Sodium (Na+) 136-145 mEq/L
Chloride (Cl-) 95-105 mEq/L
Potassium (K+) 3.5-5.0 mEq/L
Bicarbonate (HCO3-) 22-28 mEq/L
Magnesium (Mg2+) 1.5-2.0 mEq/L
Estriol, total, serum (in pregnancy)  
24-28 wks // 32-36 wks 30-170 ng/mL // 60-280 ng/mL
28-32 wk // 36-40 wks 40-220 ng/mL // 80-350 ng/mL
Ferritin, serum Male: 15-200 ng/mL
Female: 12-150 ng/mL
Follicle-stimulating hormone, serum/plasma Male: 4-25 mIU/mL
Female: premenopause: 4-30 mIU/mL
midcycle peak: 10-90 mIU/mL
postmenopause: 40-250
pH 7.35-7.45
PCO2 33-45 mmHg
PO2 75-105 mmHg
Glucose, serum Fasting: 70-110 mg/dL
2-h postprandial:<120 mg/dL
Growth hormone - arginine stimulation Fasting: <5 ng/mL
Provocative stimuli: > 7ng/mL
Immunoglobulins, serum  
IgA 76-390 mg/dL
IgE 0-380 IU/mL
IgG 650-1500 mg/dL
IgM 40-345 mg/dL
Iron 50-170 μg/dL
Lactate dehydrogenase, serum 45-90 U/L
Luteinizing hormone, serum/plasma Male: 6-23 mIU/mL
Female: follicular phase: 5-30 mIU/mL
midcycle: 75-150 mIU/mL
postmenopause 30-200 mIU/mL
Osmolality, serum 275-295 mOsmol/kd H2O
Parathyroid hormone, serume, N-terminal 230-630 pg/mL
Phosphatase (alkaline), serum (p-NPP at 30° C) 20-70 U/L
Phosphorus (inorganic), serum 3.0-4.5 mg/dL
Prolactin, serum (hPRL) < 20 ng/mL
Proteins, serum  
Total (recumbent) 6.0-7.8 g/dL
Albumin 3.5-5.5 g/dL
Globulin 2.3-3.5 g/dL
Thyroid-stimulating hormone, serum or plasma .5-5.0 μU/mL
Thyroidal iodine (123I) uptake 8%-30% of administered dose/24h
Thyroxine (T4), serum 5-12 μg/dL
Triglycerides, serum 35-160 mg/dL
Triiodothyronine (T3), serum (RIA) 115-190 ng/dL
Triiodothyronine (T3) resin uptake 25%-35%
Urea nitrogen, serum 7-18 mg/dL
Uric acid, serum 3.0-8.2 mg/dL
Hematologic Reference Range
Bleeding time 2-7 minutes
Erythrocyte count Male: 4.3-5.9 million/mm3
Female: 3.5-5.5 million mm3
Erythrocyte sedimentation rate (Westergren) Male: 0-15 mm/h
Female: 0-20 mm/h
Hematocrit Male: 41%-53%
Female: 36%-46%
Hemoglobin A1c ≤ 6 %
Hemoglobin, blood Male: 13.5-17.5 g/dL
Female: 12.0-16.0 g/dL
Hemoglobin, plasma 1-4 mg/dL
Leukocyte count and differential  
Leukocyte count 4,500-11,000/mm3
Segmented neutrophils 54%-62%
Bands 3%-5%
Eosinophils 1%-3%
Basophils 0%-0.75%
Lymphocytes 25%-33%
Monocytes 3%-7%
Mean corpuscular hemoglobin 25.4-34.6 pg/cell
Mean corpuscular hemoglobin concentration 31%-36% Hb/cell
Mean corpuscular volume 80-100 μm3
Partial thromboplastin time (activated) 25-40 seconds
Platelet count 150,000-400,000/mm3
Prothrombin time 11-15 seconds
Reticulocyte count 0.5%-1.5% of red cells
Thrombin time < 2 seconds deviation from control
Volume  
Plasma Male: 25-43 mL/kg
Female: 28-45 mL/kg
Red cell Male: 20-36 mL/kg
Female: 19-31 mL/kg
Cerebrospinal Fluid Reference Range
Cell count 0-5/mm3
Chloride 118-132 mEq/L
Gamma globulin 3%-12% total proteins
Glucose 40-70 mg/dL
Pressure 70-180 mm H2O
Proteins, total < 40 mg/dL
Sweat Reference Range
Chloride 0-35 mmol/L
Urine  
Calcium 100-300 mg/24 h
Chloride Varies with intake
Creatinine clearance Male: 97-137 mL/min
Female: 88-128 mL/min
Estriol, total (in pregnancy)  
30 wks 6-18 mg/24 h
35 wks 9-28 mg/24 h
40 wks 13-42 mg/24 h
17-Hydroxycorticosteroids Male: 3.0-10.0 mg/24 h
Female: 2.0-8.0 mg/24 h
17-Ketosteroids, total Male: 8-20 mg/24 h
Female: 6-15 mg/24 h
Osmolality 50-1400 mOsmol/kg H2O
Oxalate 8-40 μg/mL
Potassium Varies with diet
Proteins, total < 150 mg/24 h
Sodium Varies with diet
Uric acid Varies with diet
Body Mass Index (BMI) Adult: 19-25 kg/m2
Calculator

Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
Question locked
Sorry, this question is for
PEAK Premium Subscribers only
Upgrade to PEAK
ARTICLES (2)
VIDEOS (1)
Topic COMMENTS (6)
Private Note