Flashcards in week 10 --> HD Deck (26)
What is huntington disease?
Progressive neurodegenerative disorder with motor, cognitive, pysychiatric disturbance.
Affects mood, movement and memory
What are the movement disorders caused by HD?
Chorea, dystonia, bradykinesia, swallowing/ choking, dysarthria
What are the mood disorders caused by HD?
Depression, euphoria, apathy, anxiety, aggression, psychotic symptoms
What are the cognition disorders caused by HD?
Loss of executive functioning, rigidity of thought, memory loss, dementia
What is the median age onset of HD and how survival time after diagnosis?
Mean age of onset is 35 to 44 years but can range from 2-80yrs.
Median survival rate is 15-18 years after onset
What does Chorea mean?
Uncrotrolled movemement that you are not expecting to make --> no purpose
What is the genetic cause of HD?
Autosomal dominant disorder
Complete penetrance --> everyone that inherit the genetic mutation will get it
HTT gene at 4q16.3
Normal HTT gene contains, within exon 1, a run of CAG trinucleotide repeats
What happens to the CAG trinucleotide repeat in a person with HD?
The HD mutation causes expansion of the CAG repeat to be greater than 40. Which is seen as the cut of point for the caue of HD.
Very few cases of 36-39 CAG repeats causing HD.
What is the action of HD at protein level?
Abnormal protein – increased number of glutamine amino acids = polyglutamine (polyQ) expansion which alters protein structure and biochemical properties.
PolyQ cellular protein aggregates form – unknown if they cause disease
Where in the brain does the abnormal proteins formed by the HD mutation affect?
Basal gnaglia especially caudate nucleus primarily affected
What is a definition of anticipation?
The onset of a disorder occurs at an earlier age as it is passed from one generation to the next. Often this is associated with an increase in severity of symptoms
What is anticipation assoicated with?
Assoicated wtih triplet repeat disorders
What is the consequence of anticpiation on triplet repeat disorders?
Triplet repeat expansions are unstable and may increase (occasionally contract) when passed to the next generation
The phenomenon of anticipation is often linked to the gender of the parent. State the high anticipation risk for Hd, Myotonic dystropy and Fragile X syndrome.
Also state the mode of inheritance?
HD--> Autosomal dominant inheritance --> higher anticipiation risk if its from parternal inheritance.
MD --> AD inheritance --> Maternal inheritance
Fragiel X syndrome --> XL recessive --> maternal inheritance
What affects the age of onset of HD?
The size of expansion of CAG repeat
When is predictive gene testing used for HD?
When the patient is aymptomatic but has a family history of HD. So trying to predict whether or not the person with get HD
What is investigated in gene testing for Hd?
The number of CAg repeats
What is HD predictive testing?
Different to convential medical testing which defines a person current condition.
It is testing someone who is asymptomatic and predicting in advance whether they will get HD --> cannot tell you when thou and how bad it will be
What other diseases can predictive testing be used on?
BRCA (familial breast cancer genes)
HNPCC (Hereditary non-polyposis colon cancer)
What is the aim of predictive testing in terms of treatment of HD?
Hope that early identification leads to reduced morbidity and mortality through targeted screening, surveillance and prevention
What are the treatments of HD?
Symptomatic treatment only at present
No prevention or cure
Testing does not save lives
What are reasons for testing for HD?
Just ‘want to know’
Plan future care
Want to plan their career
Make decisions about children
Inform other relatives whose risk may change
What is the chance of a child having HD if one of there parents have it?
Can a embryo be tested for HD?
Yes a genetic test of the embryo can be done and the ones with the HD mutation can be discarded
What is the limitations of predictive testing?
While if positive is certanity of full penetrance it does not tell you how bad it will be, when will it happen and the course.