Lecture 33 - Other Muscular Dystrophies Flashcards
Do causative genes for muscular dystrophies have a uniform effect?
No. Have variable effects.
What are the classifications of MDs based on? 1) 2) 3) 4) 5) 6)
1) Age of onset
2) Patterns of inheritance
3) Patterns of weakness
4) Involvement of other systems
5) Patterns of abnormality on muscle biopsies
6) Causative gene (where identified)
Why make a specific diagnosis of a MD? 1) 2) 3) 4)
1) Know course of disease, be able to tell patient prognosis
2) To be able to watch for complications
3) To avoid giving inappropriate treatment
4) To give genetic counselling
Benefits of genetic counselling
1)
2)
3)
1) See recurrence risk in siblings
2) Counsel other family members
3) See when being a carrier is a health risk
What is a MD that is infant-onset?
Congenital muscular dystrophy
What is a MD that is adult-onset?
Limb-girdle muscular dystrophy
Normal response of a baby being picked up by their back
Flexion of back, neck
MD with a focal pattern of weakness
Rigid spine syndrome (significant, early, spinal weakness)
Facial weakness
1)
2)
3)
1) Blank expression
2) Tented upper lip
3) Mouth often open
Other systems that can be affected in MDs 1) 2) 3) 4)
1) Brain
2) Musculoskeletal
3) Ocular
4) Endocrine
Brain involvement in MDs
1)
2)
1) Abnormalities of brain development or maturation
2) Cognitive impairment
Musculoskeletal effects of MDs
1)
2)
3)
1) Muscle weakness
2) Joint contractures (elbow, Achilles tendon, iliotibial band)
3) Spinal rigidity, scoliosis
Eye effects of MDs
1)
2)
1) Structural or retinal abnormalities
2) Cataracts
Mutations in which gene can cause congenital muscular dystrophy?
FKRP gene
Effects of FKRP gene mutation
1)
2)
3)
1) Congenital muscular dystrophy
2) Signature mental retardation
3) Cerebellar cysts
Appearance of congenital muscular dystrophy muscle biopsy
1)
2)
3)
1) Increased central nuclei
2) Increased fat infiltration
3) Increased fibrous tissue
Ways to use a muscle biopsy to diagnose MDs
1)
2)
3) a, b, c, d
1) Histology
2) Electron microscopy
3) Diagnostic screen
a) Immunohistochemistry
b) Western blot
c) Mutation analysis
d) Biochemical analysis
Immunohistochemisty
Staining with fluorescent antibodies
Alpha-dystroglycan immunohistochemical staining in normal muscle
Continuous, homogenous bands surrounding muscle fibres
Alpha-dystroglycan immunohistochemical staining in MD muscle
1)
2)
1) Incomplete or absent staining around muscle fibres
2) As it is attached to other proteins, can cause apparent absence of other proteins in dystroglycan complex too
Myotonic dystrophy mode of inheritance
Autosomal dominant
Prevalence of myotonic dystrophy
1/8000
Which chromosome is myotonic dystrophy inherited on?
Chr19
Myotonic dystrophy effects 1) 2) 3) 4) 5) 6) 7)
1) Multisystem disorder
2) Proximal and distal wasting and weakness
3) Smooth muscle involvement. Constipation, uterine problems
4) Cognitive defects
5) Excessive somnolence
6) Cataracts
7) Endocrine dysfunction (diabetes, infertility)
MD that shows anticipation
Myotonic dystrophy
What is anticipation?
Shows worse phenotype with successive generations
Muscle biopsy of myotonic dystrophy
Very non-specific
How are tests for muscular dystrophies conducted?
1)
2)
1) Specific, targeted
2) Specific stains (for proteins), histological findings are suggested, based on clinical examination
Common muscular feature of myotonic dystrophy
Foot drop
Most common adult MD
Myotonic dystrophy (DMD is more common overall, but DMD patients don’t survive to adulthood)
IQ of congenital myotonic dystrophy patients
Normally between 50 and 70
Muscles commonly affected in myotonic dystrophy 1) 2) 3) 4) 5)
1) Arms, forearms
2) Feet, legs
3) Neck
4) Facial muscles
5) Intestinal smooth muscle, heart
Three phenotypes of myotonic dystrophy
1) Congenital
2) Classical
3) Mild
Congenital myotonic dystrophy 1) 2) 3) 4)
1) Most severe phenotype
2) Presents in first 4 weeks of life
3) Respiratory failure, feeding problems
4) Early death common