BIOM30002 Lecture Notes - Lecture 16: Muscular Dystrophy, Muscle Biopsy, Scoliosis
12 Jun 2018
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L16 Other muscular dystrophies
Summary
- The numerous human muscular dystrophies share muscle weakness as a defining feature
- Which muscles are involved can vary widely
- Many MD involve other organs - multisystem
- Diagnosis of these conditions is based on clinical, neurophysiologic, pathological and genetic
tests
- Understanding the genetic and molecular basis of these conditions is vital for identifying
specific therapies
Classification of MD
- Age of onset
- Pattern of weakness
- Pattern of inheritance
- Involvement of other systems
- Specific abnormalities on muscle biopsy, but usually genetic test
- Causative gene where identified
Age of onset
1. Infantile: congenital MD, poor head control
2. Adult onset: limb-gridle MD
Pattern of weakness
- Generalised
1. Facial weakness
2. Flexed joints
- Focal: rigid-spine syndrome
1. Lumbar lordosis
2. Scoliosis
Inheritance pattern
- 50%, due to autosomal
Involvement of other systems
1. Brain
Cognitive abnormalities
Brain development/maturation
2. Musculoskeletal
Scoliosis, lumbar lordosis
Joint contractures (Achilles (ankle), ITB (hip), elbow and wrist); flexed
3. Endocrine system
Puberty issue, infertility
Diabetes
4. Eye
Cataracts
Structure/retinal abnormalities
Myotonic dystrophy (DM1)
- Autosomal dominant (1/8000)
- Chromosome 19
- Multisystem disorder
1. Proximal and distal weakness
2. Wasting, facial weakness, myotonia
3. Smooth muscle involvement: GIT, uterine, bladder
4. Cognitive deficits, excessive somnolence, personality
5. Cardiac – conduction abnormalities, arrhythmias
6. Retinal - Cataracts
7. Endocrine dysfunction: diabetes, infertility
8. Muscle biopsy: non-specific, Ringbinden
Clinical findings
- 3 phenotypes
1. Congenital
Most severe
First 4w of life/neonatal
Respiratory failure, feeding difficulties and early death common
Severe hypotonia – floppy baby
Facial + proximal muscle weakness
Delayed motor development
Severe intellectual deficits
2. Classic DM1
Most common
Intermediate
Adolescence/adulthood
Muscle weakness
3. Mild DM1
Cataract
Mild myotonia: inability to relax voluntary muscle
Mild muscle weakness
Can be missed
Muscle biopsy
1. Central nuclei
2. Ringbinden: myofibrils wrapped creating a tight spiral
Molecular pathogenesis of DM1
- Expanded CTG repeats in gene DMPK
1. Normal: 5-35 CTG repeats
2. Pre-mature: 35-49 CTG repeats risk, symptomatic
3. Fully penetrant: >50 CTG repeats DM1
- Autosomal dominant
- Anticipation
1. offspring – longer CTG repeats expanded during meiosis (sperm/oocytes)
2. increase disease severity and decrease age onset
Document Summary
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