Neurogenetics Flashcards
Duchenne muscular dystrophy:
-inheritance
x-linked recessive
sporadic in 1/3
What is duchenne muscular dystrophy?
Muscular dystrophies are a group of inherited conditions with an intrinsic defect of muscle.
They are characterized by progressive wasting and weakness
DMD is where the pelvic/shoulder girdle muscles are affected
What are the s/s of duchenne muscular dystrophy?
Delay in motor development Onset of weakness ~ 3-4 years pelvic and shoulder girdles characteristic posture Calf hypertrophy Wheelchair bound by 10-12 years Death from involvement of respiratory and cardiac muscles in 20s
What is the genetic mutation is duchenne muscular dystrophy?
dystrophin gene
What is the diagnosis of duchenne muscular dystrophy?
developmental delay in boys
muscle weakness
Gower’s sign
toe walking
raised serum creatine kinase (CK)
-CK is a vague marker for muscle disease but in context of other signs/symptoms useful
Electromyography (EMG) – characteristic electrical signs
muscle biopsy – can back up the genetic test
molecular genetic testing
- screen for deletions
Describe the carrier testing for duchenne muscular dystrophy
identify mutation in affected boy
test for mutation in female relatives wishing to know carrier status
female carriers of known dystrophin mutations can be offered prenatal testing
What is beckers muscular dystrophy?
milder form of duchenne muscular dystrophy:
- Later onset (teens and early twenties)
- Mutation in dystrophin
- Slower progress
Huntingdons disease - inheritance?
autosomal dominant chromosome 4
What is huntingdons disease
Progressive neurodegenerative disorder
Onset usually between 30 and 50 years
Involuntary movements
Dementia
Progression to severe dependency and deathover 15-20 years
What are the early clinical signs of huntingdons disease?
Clumsiness Agitation Irritability Apathy Anxiety Disinhibition Delusions Hallucinations Abnormal eye movements Depression
What are the late clinical signs of huntingdons disease?
Dystonia Involuntary movements Trouble with balance and walking Trouble with activities that require manual dexterity Slow voluntary movements Difficulty initiating movement Inability to control speed and force of movement Weight loss Speech difficulties Stubbornness
What are the end stage clinical signs of huntingdons disease?
Rigidity Bradykinesia (difficulty initiating and continuing movements) Severe chorea (less common) Serious weight loss Inability to walk Inability to speak Swallowing problems, danger of choking Inability to care for oneself
What is the pathogenesis of huntingdons disease?
Condition is characterised by loss of neurons in basal ganglia and especially the caudate nucleus
- caused by more than 36 CAG repeats in the huntingdon gene
- this displays penetrance (as it gets passed down, the younger those are affected)
What gene is implicated in genetic alzheimers?
- ApoE
- ApoE 4 predisposes to alzheimers
- ApoE 2 is assoc. with longevity
