Predisposition to Adult Onset Disease Flashcards
Why are adults referred to genetics?
Diagnosis Predictive testing Carrier testing Cascade screening (after one family member is diagnosed) Family history (including cancer) foetal loss or recurrent miscarriages
Mechanisms of adult onset genetic disease
Single gene
Chromosomal
Mitochondrial
Multifactorial i.e. +environment
What is penetrance?
The concept of the person having a genetic variant and the likelihood of getting the disease associated with it
Risk estimation of a disease is easier if the disorder is….
Single gene
High penetrance
Features of a multifactorial condition
A polygenic genetic component interacting with environmental factors
Risk estimation more difficult
Risk alleles being identified for common / multifactorial disease
Ethics in medicine
Respect for autonomy
Beneficence
Non-maleficence
Justice
What conditions is the most predictive testing done in?
Huntington’s disease (most common)
Familial cancer syndromes
Cardiac disease
Age of onset of motor neurone disease
55 years
Younger in familial forms
Genetics of motor neurone disease
generally sporadic
5-10% familial (AD+AR)
Presentation of motor neurone disease
Progressive muscle weakness progressive muscle wasting Progressive increased reflexes BOTH UPPER AND LOWER MOTOR NEURONE SIGNS limb and bulbar muscles involved pure motor signs (with fasciculations) cognition spared Death due to respiratory failure
Another name for motor neurone disease
Amyotrophic lateral sclerosis
A mutation in which gene causes familial motor neurone disease?
Cu/Zu superoxide dismutase (SOD)
What does Cu/Zu superoxide dismutase do?
Catalyses conversion of intracellular superoxide radicals produced during normal metabolism
Motor neurones express it highly
So the presence of SOD protects may types of cells from free radical damage that is important in ageing and ischaemic tissue damage
Helps protect cells from DNA damage and other forms of progressive cell degradation
Penetrance of Motor neurone disease
Incomplete penetrance
Treatment of motor neurone disease
No treatment
No cure
Features of huntington’s disease
Autosomal dominant Adult onset - late 30s/40s but variable duration 15-20 years unique mutation - CAG expansion fully penetrant
Duration of huntington’s disease
15-20 years
Penetrance of Huntington’s disease
Fully penetrant
Mutation of Huntington’s disease
CAG expansion
Presentation of Huntington’s Disease
Movement disorder - chorea - athetosis - myoclonus - rigidity Cognitive changes - poor planning and memory - subcortical dementia (executive function) - NOT classical dementia Personality change - "a different person" - irritable - apathetic - loss of empathy - disinhibition - self centred Psychiatric disease - depression - paranoia - psychosis
Treatment of Huntington’s disease
No cure
Unsatisfactory treatments
some treatments for psychiatric component of the disease
