nuerogenetics

Question 1

Duchenne muscular Dystrophy

• inheritance?
• progression of disease?
• presentation?
• deficiency of what? consequence?
• Diagnosis?
• DDx?
• carrier testing?

Answer 1

-X-likned recessive condition

-delay in motor development and then weakness around 3-4 yrs of pelvic girdle and shoulders
wheelchair bound by 10-12 years
Death in 20s from cardio/resp involvement

-proximal muscle wasting, exaggerated lumbar lordosis, characteristic posture
calf hypertrophy

-Dystrophin deficiency
caused by mutations in the dystrophin gene
dystrophin normally connects the contractile elements in muscles, the proteins connect through cells in the extracellular matrix so muscles cannot be renewed

-Developmental delay in boys
muscle weakness: Gower’s sign and toe walking
raised CK
electromyography
Muscle biopsy
molecular genetic testing + screen for deletions

• autosomal recessive limb girdle muscle dystrophies
• identify the mutation in the affected boy the test for the mutation i female relatives, if present can be offered

Question 2

Huntington disease

• what is it?
• inheritance?
• presentation?
• penetrance?
• early clinical signs? (9)
• later clinical signs? (10)
• Late clinical signs? (8)
• brain changes?
• changes to what gene?
• predictive testing?

Answer 2

• progressive neurodegenerative disorder
• autosomal dominant
• chorea, dementia, progression over 15-20 years
• age dependent, normally between 30-50

-Clumsiness
Agitation 
Irritability
Apathy
Anxiety 
Disinhibition 
Delusions/hallucinations
abnormal eye movements 
Depression 

-Dystonia
Involuntary movements
trouble with balance and walking 
reduced manual dexterity
slow voluntary movement
difficulty initiating movement 
inability to control speed and force of movement 
Weight loss
Speech difficulties Stubbornness 

-Rigidity
Bradykinesia 
Severe Chorea
Serious weight loss
inability to walk
inability to speak 
swallowing probs- choking danger
inability to car for oneself 

-caudate atrophy

-Huntington gene
(get longer CAG region) CAG codes for glutamine which has a direct neurotoxic effect

-implications for work, financial implications, coping, pre-natal testing etc

Question 3

Alzheimers disease

• age of onset?
• inheritance?
• 3 pathological characteristics?
• genetic component?
• important protein?

Answer 3

• common cause of dementia, usually occurs in old age
• genetic heterogeneity, some clusters in families

-loss of cortical neurones
Neurofibrillary tangles
Senile plaques (amyloid deposits)

-Down syndrome predisposes
APP mutations (chromosome 21)
Presenilin 1/2
(chromosomes 14/1)

-Apiloprotein E (ApoE)
the e4 allele predisposes to Alzheimers disease

Question 4

Multiple sclerosis

• inheritence?
• genetic component?

Answer 4

• multifactorial, clustering in families

- mor common in those with certain MHC haplotypes