Muscular dystrophy Flashcards
Define muscular dystrophies and give examples
Group of inherited disorders with progressive muscle degeneration, characterised by muscle weakness and wasting of variable distribution and severity
Duchenne muscular dystrophy
Becker muscular dystrophy
Limb girdle muscular dystrophies
Congenital muscular dystrophies
What is the aetiology of Duchenne Muscular dystrophy
X-linked recessive disorder (xp21)
Deletion of the gene for dystrophin (connects the cytoskeleton of a muscle fibre to the surrounding extracellular matrix through the cell membrane)
Deficient dystrophin → calcium ion influx → breakdown of calcium calmodulin complex → excess free radicals → progressive myofibre necrosis
What are the symptoms and signs of Duchenne muscular dystrophy
Waddling gait
Toe-walking
Language delay
Mounting stairs one by one
Run slowly compared to peers
Slower and clumsier than peers
No longer able to walk by 10-14 years old (due to the progressive muscle atrophy and weakness)
Gower’s sign (need to turn prone in order to rise >3yo)
Pseudohypertrophy of the calves (replacement of muscle by fat and fibrous tissue
What investigations should be done for Duchenne muscular dystrophy
Bloods: Creatine kinase (CK) = elevated
Other:
- EMG: Establishes myopathic nature, exclude neurogenic causes of muscle weakness
- Muscle biopsy: immunostaining for dystrophin
- Lung function testing: reduced muscle strength → decreased vital capacity
What is the management for Duchenne Muscular Dystrophy
MDT management
OT/PT: moderate physical exercise, mobility aids, night splints, spinal support
Corticosteroids
Atluren (allows bypass of the mutation and production of a small amount of dystrophin
Education
Psychological support and counselling
Genetic counselling
Systemic support
Early and aggressive cardiomyopathy management
Respiratory care and assisted respiration
Immunisation (pneumococcal, influenza)
Prophylactic Abx
Orthopaedic: tendoachilles lengthening, scoliosis surgery
OSA → overnight CPAP
What are the complications of Duchenne muscular dystrophy
Respiratory failure
Cardiomyopathy → cardiac failure
Loss of mobility
Learning difficulties
Scoliosis
OSA
Weight loss/malnutrition
Osteoporosis, vertebral compression fractures
Sexual dysfunction
What is the prognosis for Duchenne Muscular dystrophy
Often not walking by 10-14yo
- 10yo: needs braces to walk
- 12yo: most are wheelchair-bound
Life expectancy reduced to the late twenties from respiratory failure or cardiomyopathy
What is the aetiology of Becker muscular dystrophy
Allelic with Duchenne muscular dystrophy (different mutations, same gene)
Some functional dystrophin is produced (30-80% normal)
Exon deletions exist in the dystrophin gene Xp21 in 70% cases
What are the signs and symptoms of Becker muscular dystrophy
Similar to Duchenne muscular dystrophy, but milder and progresses more slowly
Average age of onset = 11yo
Learns to walk later than usual
Muscle cramps after exercise
Struggles with sports at school
Struggling with lifting objects
What is the prognosis for Becker muscular dystrophy
Loss of independent ambulation in the late 20s
Life expectancy well into middle or old age
Describe limb girdle muscular dystrophies
Proximal upper and lower limb weakness
Cardiomyopathy and difficulty with breathing
Plasma CK raised
Describe congenital muscular dystrophies
Autosomal recessive inheritance
Presents at birth or early infancy
Muscle biopsy: dystrophic features with reduction of one of the extracellular matrix proteins e.g. laminin
What are the signs and symptoms of congenital muscular dystrophies
Presents at birth or early infancy
Proximal weakness, slowly progressive
Hypotonia
Contractures (contracture when the ability to walk is lost)
Feeding difficulties
Breathing difficulties
Intellectual disability
What is the aetiology of myotonic dystrophy
Autosomal dominant
Most common adult-onset muscular dystrophy (20-30s)
Expansion of CTG nucleotide triplet on the DMPK gene (Chr19)
Holds genetic anticipation (earlier onset in offspring)
What are the signs and symptoms of myotonic dystrophy
Perinatal: oligohydramnios, reduced foetal movements
Infants: hypotonia, feeding difficulties, resp. difficulties, talipes
Children:
- Myotonic facial appearance
- Learning difficulties
- Myotonia, hypotonia
- Progressive muscle loss and weakness (smaller > larger)
- Thin ribs
Adults: cataracts, blindness, testicular atrophy, T2DM, slow release of handshake, difficulty releasing a tightly clasped fist, cardiac arrhythmia
