Huntington's Disease Flashcards
Give an account of the pattern of inheritance for Huntington's gene carriers, describing the genetic defect and underlying mutation responsible for Huntington's disease Describe the neuropathological changes that occur in the brain of Huntington's disease carriers and the early and later symptoms characteristic of Huntington's disease Discuss the principle brain imaging which can be utilised to assess pathology in the Huntington's disease brain and to monitor changes in brain function following
What is the UK prevalence of Huntington’s disease?
12.3 per 100,000
What is the mean age of onset of Hutington’s disease?
30-50
A mutation in which gene causes Huntington’s disease, and which chromosome is it on?
HTT - chromosome 4 (4p16.3)
What type of mutation causes Huntington’s disease?
An improper expansion of the CAG trinucleotide
What does the mutation in Huntington’s disease do to the Huntingtin protein?
It causes formation of an abnormal form with large glutamine blocks
Which neurons are most affected by abnormal HTT?
medium spiny GABA-ergic neurons in the caudate and putamen
Name the structures functionally defined as the basal ganglia
Striatum, globus pallidus, ventral pallidum, substantia nigra, subthalamic nucleus
Name the structures of the dorsal striatum
Caudate and putamen
Name the structures of the ventral striatum
Nucleus accumbens and olfactory tubercle
Describe the pathological features seen in Huntington’s disease brains at autopsy
Marked brain atrophy and enlargement of the ventricles, with particular atrophy of the basal ganglia
Describe the early symptoms of Huntington’s disease
Choreic movements, stumbling, clumsiness, lack of concentration, short-term memory lapses, depression, changes of mood - e.g. aggressive or antisocial behaviour
Describe the late symptoms of Huntington’s disease
Incapacitating choreic movements, loss of coordination and balance, difficulty eating and swallowing, cognitive decline and dementia, death after 10-15 years
Name the rating scale used to assess Huntington’s disease for research purposes
Unified Huntington’s disease rating scale (UHDRS)
State the contents of the unified Huntington’s disease rating scale
Motor assessment, cognitive assessment, verbal fluency test, symbol digit modalities test, behavioural assessment, functional assessment, independence scale
How many CAG repeats can the HTT gene have and still be in the normal range?
<28
