Also known as: HD, Huntington chorea, Huntington's disease
Overview
An autosomal dominant neurodegenerative disorder caused by an expanded CAG repeat in the huntingtin (HTT) gene on chromosome 4p. Characterized by the clinical triad of movement disorder (chorea), psychiatric disturbance, and dementia.
Epidemiology
Prevalence ~5-10 per 100,000 in populations of European descent; lower in Asian and African populations. Mean age of onset 35-45 years. Juvenile-onset (<20 years) tends to inherit paternally and present with rigidity and seizures (Westphal variant).
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Question 1NeurologyMedium
A 48-year-old man with a family history of an autosomal dominant neurodegenerative disease presents with progressive chorea, irritability, and cognitive decline. Genetic testing reveals 44 CAG trinucleotide repeats in the HTT gene. As his disease progresses over the next decade, which of the following complications is he most likely to develop?
ASensorineural hearing loss
BCardiac conduction block
CPeripheral sensory neuropathy
DAspiration pneumonia
EStatus epilepticus
Reveal answer & full explanation
Correct answer: D — Aspiration pneumonia
ASensorineural hearing loss
BCardiac conduction block
CPeripheral sensory neuropathy
DAspiration pneumonia✓
EStatus epilepticus
Why Aspiration pneumonia is correct
Huntington disease is an autosomal dominant disorder caused by CAG trinucleotide repeat expansion in the HTT gene, leading to neuronal loss in the striatum and cortex.
Progressive motor dysfunction includes chorea, dystonia, and eventually bulbar involvement with dysphagia.
Aspiration pneumonia is the most common cause of death in Huntington disease, driven by impaired swallowing and weakened cough.
Why the others are wrong
Peripheral sensory neuropathy — Huntington disease destroys striatal medium spiny neurons and cortex; the peripheral nerves are spared, so stocking-glove sensory loss is not part of its natural history.
Sensorineural hearing loss — The HTT expansion does not damage the cochlea or central auditory pathways; hearing loss in these patients reflects age-related presbycusis rather than disease progression.
Status epilepticus — Seizures and status epilepticus can occur in juvenile-onset Westphal variant but are uncommon in adult Huntington disease and are not the leading complication.
Cardiac conduction block — Huntington disease shares autosomal dominant inheritance, a trinucleotide-repeat expansion, and anticipation with myotonic dystrophy type 1, whose classic life-threatening complication is cardiac conduction block, so the two are easy to conflate; but conduction block is not a characteristic complication of Huntington disease, whose decline runs through dysphagia to aspiration.
Question 2NeurologyMedium
A 42-year-old man is brought in by his wife for 8 months of involuntary fidgety movements of his hands and face and a year of worsening irritability and apathy. His father died in a nursing home with dementia and a "movement problem." On exam he has brief, irregular, dance-like movements that flit between body parts, slow eye saccades, and inability to keep his tongue protruded. Mental status shows slowed processing and impaired executive function with relatively preserved memory. Which of the following is the most appropriate next diagnostic test?
ABrain MRI with caudate volumetry
BHTT gene CAG repeat genetic testing
CAnti-streptolysin O antibody titer
DSerum ceruloplasmin and urine copper
EDopamine transporter SPECT imaging
Reveal answer & full explanation
Correct answer: B — HTT gene CAG repeat genetic testing
ABrain MRI with caudate volumetry
BHTT gene CAG repeat genetic testing✓
CAnti-streptolysin O antibody titer
DSerum ceruloplasmin and urine copper
EDopamine transporter SPECT imaging
Why HTT gene CAG repeat genetic testing is correct
The vignette is a textbook presentation of Huntington disease: adult-onset chorea, psychiatric change (irritability, apathy), subcortical dementia (executive dysfunction with preserved memory), slow saccades and motor impersistence, plus an autosomal dominant family history (father with dementia and a movement disorder).
Diagnosis is confirmed by measuring the CAG trinucleotide repeat number in the huntingtin (HTT) gene: >=40 is fully penetrant and >=36 is diagnostic in a symptomatic patient. This is both the confirmatory and the definitive next study once HD is clinically suspected.
Because the patient is symptomatic, this is diagnostic testing rather than presymptomatic predictive testing, though genetic counseling still accompanies it given implications for at-risk relatives.
Why the others are wrong
Serum ceruloplasmin and urine copper screen for Wilson disease, a real chorea mimic, but Wilson typically presents in a younger patient with hepatic dysfunction and Kayser-Fleischer rings; here the dominant inheritance pattern and classic HD phenotype point elsewhere, making this a non-discriminating mimic workup rather than the confirmatory test.
Brain MRI with caudate volumetry may show caudate atrophy with enlarged frontal horns, but this is a late, nonspecific finding and a normal MRI does not exclude HD; imaging does not establish the diagnosis the way the genetic test does.
Anti-streptolysin O antibody titer evaluates for Sydenham chorea, a post-streptococcal disorder of children and young adults that is self-limited; it does not fit a 42-year-old with progressive dementia and dominant inheritance.
Dopamine transporter SPECT imaging — tempting because HD is a basal ganglia disorder, but DaT-SPECT is used to separate presynaptic dopaminergic parkinsonian syndromes from mimics such as essential tremor; it is not a diagnostic test for chorea and cannot confirm HD the way CAG repeat testing does.
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Affected parent (autosomal dominant inheritance; 50% risk to each offspring)
Paternal transmission predisposes to anticipation — earlier onset and longer repeat in next generation
CAG repeat length: ≥40 fully penetrant; 36-39 reduced penetrance; 27-35 intermediate (no disease but risk of expansion); ≤26 normal
Pathophysiology
Expanded CAG repeats produce mutant huntingtin protein with an elongated polyglutamine tract that misfolds, aggregates, and causes selective neuronal degeneration. Medium spiny GABAergic neurons of the striatum are preferentially lost, particularly those projecting to the lateral globus pallidus (indirect pathway), producing disinhibition of thalamocortical drive and chorea. Cortical neurodegeneration contributes to cognitive decline.
Clinical presentation
Symptoms
Movement: chorea (early), dystonia, bradykinesia, dysarthria, dysphagia, gait impairment; rigidity in juvenile or late disease
Psychiatric (often the first complaint): depression, irritability, apathy, anxiety, obsessive-compulsive features, psychosis; elevated suicide risk
Cognitive: subcortical dementia with executive dysfunction, impaired attention, and slowed processing — memory relatively preserved until later
Weight loss despite adequate caloric intake
Signs / physical exam
Chorea — involuntary, brief, irregular, dance-like movements that flit from one body part to another
Motor impersistence ('milkmaid grip' — inability to maintain sustained tongue protrusion or hand grip)
Abnormal saccades — slow and hypometric, often the earliest motor sign
Oculomotor apraxia (head thrust to initiate gaze)
Hyperreflexia and gait instability
Classic findings
Adult with new chorea + family history of dementia or movement disorder + early personality change.
Differential diagnosis
Sydenham chorea — Post-streptococcal, children/young adults, self-limited, jerking movements with hypotonia, anti-streptolysin O
Wilson disease — Young adult with movement disorder + hepatic dysfunction, Kayser-Fleischer rings, low ceruloplasmin, high 24-h urinary copper
Educational use only. This outline is a study aid for PA students and is not medical advice or a substitute for clinical judgment. FirstPassPA is an independent study tool and is not affiliated with, endorsed by, or sponsored by NCCPA or PAEA. PANCE® and PANRE® are registered trademarks of the National Commission on Certification of Physician Assistants; End of Rotation™ is a program of the Physician Assistant Education Association.