Muscular Dystrophies
Muscular Dystrophies: Excerpt from The 5-Minute Pediatric Consult
Molly E. Rideout, MD
Muscular Dystrophies - BASICS
Muscular Dystrophies - description
Muscular dystrophies (MDs) are a heterogeneous group of disorders with progressive muscle weakness caused by mutations in genes encoding muscle proteins. The classification of MDs is complex. Currently, MDs are classified based on the following:
- Genetic mutation
- Affected protein
- Mode of inheritance
- Age of onset
- Clinical phenotype
The major types of MD are as follows:
- Duchenne (DMD)
- Becker (BMD)
- Congenital (CMD)
- Limb Girdle (LGMD)
- Myotonic Muscular Dystrophy (MMD)
Muscular Dystrophies - epidemiology
Muscular Dystrophies - incidence
- DMD—1:3,500 boys (most common type MD)
- BMD—1:30,000 boys
- CMD—1:20,000 (northeast Italy)
- MMD—1:8,000
Muscular Dystrophies - risk factors
Muscular Dystrophies - genetics
Rapid advances have been made in the field of molecular genetics to identify the myriad of genes and proteins responsible for various forms of muscular dystrophy.
- DMD, BMD: X-linked recessive, caused by mutations in the gene encoding dystrophin
- CMD: Usually autosomal recessive; caused by mutations of the basement membrane/matrix proteins (merosin/laminin 2, collagen VI), dystroglycan proteins (Fukuyama, Walker-Warburg)
- LGMD: Usually autosomal recessive; autosomal dominant cases have milder course. Recessive mutations: Sarcoglycan, Fukutin-related protein (FKRP), others
- MMD: Autosomal dominant mutations in the same gene may lead to different phenotypes.
- FKRP in severe CMD and adult-onset LGMD
- Different genes may underlie similar phenotypes (DMD and many forms of LGMD).
Muscular Dystrophies - pathophysiology
Pathology: Necrosis, fibrosis, and muscle regeneration
Muscular Dystrophies - DIAGNOSIS
Muscular Dystrophies - signs & symptoms
DMD:
- Usually presents by age 3–6
- Falls, clumsy gait, lumbar lordosis, trouble climbing stairs, arising from floor
- May have calf pseudohypertrophy
- Elevated creatine kinase (CK) levels: Apparent elevated transaminases (actually muscle origin)
- Cognitive deficits common
- Cardiac involvement
BMD:
- Presents after age 6 up to teen/adult
- Symptoms similar to those of DMD, although milder
- May have discolored urine (myoglobinuria)
- Muscle cramps are common.
- May present with dilated cardiomyopathy
CMD:
- Presents within first few months of life, usually with hypotonia or contractures
- Often with brain involvement
- 10 subtypes: More genes being identified
Subtypes:
- Merosin-deficient CMD (most common CMD):
- Profound weakness
- Nonprogressive, normal life span
- No independent ambulation
- Demyelinating neuropathy → poor peripheral motor nerve conduction
- May have normal cognitive function
- Epilepsy in 20%
- Cardiac involvement unusual
- Ullrich CMD (2nd most common CMD):
- Usually severe
- Slowly progressive
- Loss of ambulation by age 30
- Normal intelligence
- Early proximal contractures, with excessive distal laxity
- Weakness, rigid spine, prominent calcanei
- Collagen VI deficiency in many
- Fukuyama CMD:
- Carrier rate in Japan 1:90
- No ambulation
- >50% unable to speak
- Severe delayed cognitive function
- Frequent cardiac involvemen
- Seizures in 50%
- Walker-Warburg CMD:
- Most severe in group
- Severe hydrocephalus, brain abnormalities
- Severe ocular abnormalities, as above
- Life span usually <3 years
LGMD:
- Onset at any age except 1st months of life
- Currently there are 13 subtypes
- Proximal weakness pelvic → shoulder girdle
Subtypes:
- Sarcoglycanopathies (LGMD):
- Phenotype similar to DMD
- Cognitively normal
- Progressive
- Loss of ambulation by age 20
- May have dilated cardiomyopathy
- FKRP-related proteinopathy (LGMD):
- Phenotype similar to DMD
- Normal cognitive function
- Upper extremity weakness common
- Frequent dilated cardiomyopathy and respiratory failure
- May also cause CMD phenotype
- Calpainopathy:
- Slow progression, loss of walking by age 40
- Mostly atrophic, not dystrophic
- Early contractures
- Normal life expectancy
- Facioscapulohumeral MD:
- Onset by age 20
- Slow progression
- Autosomal dominant
- Weakness/wasting eye, mouth muscles
- Weak shoulders, then truncal, hip
MMD
- Teen or adult onset
- Delayed relaxation after contraction
- Affects mostly face, distal muscles
- Slow progression
- Also may affect GI, vision, cardiac, respiratory systems
- Congenital form more severe
Muscular Dystrophies - history
Antenatal:
- Decreased fetal movements, malpresentation
Neonatal:
- Torticollis
- Apnea/hypoventilation
- Feeding/growth issues
- Hypotonia
- Joint contractures
Older:
- Gross motor delays/delayed walking
- Clumsy, frequent falls
- Muscle cramps with exercise
- Global/language delays (DMD,CMD)
Muscular Dystrophies - physical exam
- Proximal muscle weakness
- Hypotonia
- Winged scapula
- Abnormal muscle bulk: Pseudohypertrophy (especially calf muscles) or atrophy
- Decreased proximal reflexes
- Sinus tachycardia (up to 50% of DMD)
- Heel cord tightness, contractures
- Lumbar lordosis
- Scoliosis (progresses with puberty)
- Ocular abnormalities (CMDs)
- Characteristic toe-walking, swaying/waddling
- Trouble climbing steps/rising from floor
- Signs of proximal muscle weakness:
- Arise from sitting on floor (abnormal >2 seconds)
- Gower maneuver: To stand from sitting, patient pushes up with arms, puts hands on knees, and “climbs up himself”
Muscular Dystrophies - tests
Muscular Dystrophies - lab
- Serum CK: Initially high, but may be low in advanced disease; lack of muscle and less mobility
- DNA tests: For DMD, CMDs, LGMDs
Muscular Dystrophies - diag proced-surgery
- MRI: Brain involvement (CMD)
- Biopsy definitive for many MDs, combined with immunohistochemistry
- Cardiac studies: EKG, ECG, 24-hour Holter monitor: 90% with DMD have tall R, prominent Q
- Pulmonary function tests (PFTs)
Muscular Dystrophies - differencial diagnosis
- Inflammatory muscle disease
- Metabolic myopathies
- Structural myopathies
- Anterior horn cell disease
- Polyneuropathy
Muscular Dystrophies - TREATMENT
Muscular Dystrophies - initial stabilization
- Consider respiratory/cardiac compromise.
- Decreased vital capacity, restrictive lung disease
- Potential dilated cardiomyopathy or arrhythmias
Muscular Dystrophies - general measures
- Supportive care
- Night splints/stretching
- Incentive spirometry
- Nocturnal bilevel positive airway pressure (BiPap)
- Scoliosis surgery (improves PFTs, comfort, survival)
- Psychological support
- Genetic counseling
Muscular Dystrophies - diet
Obesity should be addressed early as it can hasten postural decline and respiratory symptoms.
Muscular Dystrophies - activity
Encourage maintenance of independence as long as possible and physical activity.
Muscular Dystrophies - special therapy
- Stem cell research showing promising results
Respiratory measures:
- Manual/mechanical cough-assist techniques
- Noninvasive positive pressure ventilation (PPV) (NIPPV):
- Nocturnal
- Gives respiratory muscles rest
- Re-expands atelectasis
- Lowers pCO
- Mechanical ventilation:
- Negative pressure devices
- For apnea/nocturnal hypoventilation
- Tracheostomy:
- If NIPPV inadequate
- If ventilator is required 24 h/day
Muscular Dystrophies - phys therapy
Physical and occupational therapy promote mobility.
Muscular Dystrophies - medication
Steroids (in DMD): Extend walking 1–2 years
Muscular Dystrophies - FOLLOW UP
Muscular Dystrophies - prognosis
- Based on level of cardiopulmonary compromise
- DMD: More rapid progression
- BMD, LGMD: More slowly progressive
- MMD: Slowly progressive
Muscular Dystrophies - complications
Cardiac:
- Watch for dilated cardiomyopathy.
- MMD: Lethal dysrhythmias
- Scoliosis, hypoventilation, secondary cardiac dysfunction
- Cardiac muscle may be affected without skeletal muscle involvement.
- Cardiac monitoring when wheelchair-bound
- Cardiac involvement in DMD, BMD, Fukayama CMD, MMD, and LGMD subtypes 1B, 2E, 2F, 2I
Respiratory:
- Decreased vital capacity
- Impaired cough, pneumonia
Muscular Dystrophies - bibliography
- Kirschner J, Bonnemann C. The congenital and limb-girdle muscular dystrophies. Arch Neurol. 2004;61:189–197.
- Mathews K. Muscular dystrophy overview: Genetics and diagnosis. Neurol Clin. 2003;21:795–816.
Wong B, ed. Muscular dystrophies. Pediatr Ann. 2005;34(7):525–545, 560–577. www.mdausa.org
Muscular Dystrophies - CODES
Muscular Dystrophies - icd9
359.1 Muscular dystrophy
Muscular Dystrophies - PATIENT TEACHING-MED
- Muscular Dystrophy Association: www.mda.org
- Parent Project (for DMD): www.parentprojectmd.org
Muscular Dystrophies - FAQ
- Q: What is the recurrence risk in DMD?
- A: If a woman who is a carrier has a child, there is a 25% chance it will be an affected son. If she has a son, he has a 50% chance of having the disease. Her daughter has a 50% chance of becoming a carrier. Affected males transmit the gene to all daughters. Sons of affected males are unaffected. Because there are new mutations, not all mothers of probands are carriers.
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Book Source Details
- Book Title: The 5-Minute Pediatric Consult
- Author(s): M. William Schwartz MD; et al.
- Year of Publication: 2008
- Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.
More About Becker Muscular Dystrophy
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Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.
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More About This Book:
Title: The 5-Minute Pediatric Consult
Authors: M. William Schwartz MD; et al.
Publisher: Lippincott Williams & Wilkins
Copyright: 2008
ISBN: 0-7817-7577-9
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