Overview
Clinical Meaning
Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG trinucleotide repeat expansion in the huntingtin gene (HTT) on chromosome 4.
FNP
FNP
Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by CAG trinucleotide repeat expansion in the huntingtin gene (HTT) on chromosome 4. Normal HTT contains < 26 CAG repeats; 27-35 is intermediate (may expand in offspring); 36-39 shows reduced penetrance; ≥ 40 repeats causes full penetrance. The mutant huntingtin protein contains an expanded polyglutamine tract that misfolds and aggregates, forming intranuclear inclusions. Pathologically, there is selective vulnerability of medium spiny neurons (MSNs) in the caudate nucleus and putamen (striatum). These GABAergic projection neurons degenerate through multiple mechanisms: mitochondrial dysfunction (complex II/III impairment), excitotoxicity (NMDA receptor overactivation), transcriptional dysregulation, impaired BDNF transport, and proteasome dysfunction. Striatal degeneration disrupts the indirect pathway of the basal ganglia, causing chorea (excessive involuntary movements). As disease progresses and the direct pathway also degenerates, chorea decreases while rigidity and bradykinesia increase. Anticipation occurs with paternal transmission (CAG repeats tend to expand during spermatogenesis).
Unlock full lesson + practice questions
4 more sections with scenarios, priorities, and review drills.
Final rapid review before practice
Next study step
Finish the lesson first, then choose a focused activity to apply what you just reviewed.
Continue studying
Sign in to save progress on this lesson.
Unlock the interactive lesson quiz with a plan that includes this FNP pathway. You can still explore topic-filtered questions from the bank hubs below.