Predisposition to Adult Onset Disease Flashcards
What are genetic referrals for?
Diagnosis Predicitve testing Carrier testing Family history (inc. cancer) Fetal loss or recurrent miscarriages
What are the mechanisms of genetic disease?
Abnormalities in:
Single gene
Chromosomal
Mitochondrial
Multifactorial (genes + environment)
What are the issues with genetic testing?
Test info must be usable for prevention/treatment
Predictive testing requires proper counselling
Children/adolescents should only be tested if there are potential medical benefits
Third parties should have no access to the information
What is the aetiology of Amyotrophic Lateral Sclerosis (ALS)?
When is mean age of onset?
Generally sporadic (1-2/100,000) 5-10% familial - autosomal dominant + autosomal recessive
Mean age onset = 55 years
What are the clinical features of ALS?
Progressive muscle weakness + wasting
Increased reflexes
Pure motor signs
(note- cognition is spared)
What gene is affected in ALS?
What is the normal function of this gene?
Mutation to SOD gene- superoxide dismutase
~20% of familial cases
2% of all cases
SOD protects cells from free radical damage, protein denaturation etc.
What is the outcome for ALS?
Is there treatment?
Incomplete penetrance therefore even if mutation is present, no certainty of disease
No cure
No satisfactory treatment
What are the issues to be discussed prior to genetic testing?
Inheritance and its risks Implications of a positive/negative result Variability of condition Insurance Employment Future children
What is the genetic features of Huntington’s disease?
When is the typical onset?
Autosomal dominant diseaase
Unique mutation identified
Onset= late 30s/early 40s
But onset is variable
Disease if fully penetrant = all will develop signs
What are the clinical features of Huntington’s disease?
Movement disorder”
chorea, athetosis, myoclonus, rigidity
Cognitive changes: poor planning and memory
Personality change: irritable, loss of empathy
Psychiatric symptoms: depression, paranoia
What is the prognosis for Huntington’s disease?
No cure
Unsatisfactory Tx
However, good support can benefit the family and there are Tx for the psychiatric features
What are the advantages of predictive testing?
Uncertainty of gene status removed
If negative- concerns about self and offspring removed
If positive- make plans for future, arrange surveillance/treatment, inform children
What are the disadvantages of predictive testing?
If positive- removes hope, continues uncertainty, known risk to offspring, impact on self and family, potential problems with insurance/mortgage
If negative- survivor’s guilt
