Introduction to Huntington's Disease Flashcards
What kind of inheritance pattern does HD show?
HS shows autosomal dominant inheritance with anticipation leading to age-related penetrance.
What is the frequency of HD?
The frequency of HD is 3-10 / 100,000 in populations of western descent. It is must less frequent in other populations.
In one sentence outline what HD is.
HD is a progressive neurodegenerative disorder which presents with motor dysfunction, e.g. chorea, also cognitive impairment and psychiatric disturbances.
At what age do the first symptoms of HD usually manifest?
The first symptoms of HD usually manifest at approximately 35-50 years of age.
What is the duration of HD?
The duration of HD is usually approximately 15-20 years.
What % of HD cases are diagnosed before the age of 20 years?
Approximately 5-10% of HD cases present before 20 years of age (juvenile onset HD).
What are the symptoms of juvenile HD?
Symptoms of juvenile HD include rigidity, tremor, postural hypotonia, behavioural disturbance and learning difficulties.
What is the age of onset of juvenile HD?
Approximately 2-20 years.
What percentage of HD cases present after 50 years of age?
approximately 20% of HD cases present after 50 years of age.
What causes HD on the genetic level?
HD is caused by expansion of a CAG trinucleotide repeat tract in exon 1 of the huntingtin (HTT) gene (previously named IT15).
HTT is located on chromosome 4p16.3, spanning 180kb; 67 exons.
HTT is widely expressed and is required for normal development.
CAG repeats translated into a polyglutamine tract, which is thought to acquire a novel deleterious function when abnormally expanded - leading to neuronal dysfunction and neuro-degenration.
Where is HTT located?
HTT is located on chromosome 4p16.3, spanning 180kb; 67 exons.
What is a normal HTT allele size?
<27 repeats
What is an intermediate HTT allele size?
27-35 repeats - very unlikely to be affected but can expand into disease range upon transmission (especially paternal transmission).
What is a partial penetrance HTT allele size?
36-39 repeats - some individuals with repeats in this range can be unaffected at age 70-80+.
What is a ‘classic’ HTT allele size?
40-65 repeats.
What is a juvenile HD allele size?
Can be up to approximately 250 repeats (seen in an 18 month year old child).