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Huntington's disease neuropathology often turns on a piece of history rather than a single test result: a clear family history in an adult with progressive chorea (involuntary, jerky movements) points strongly to Huntington's disease, and its absence should prompt a search for other causes of chorea, especially in a younger patient. For example, imagine a child or young adult with chorea but no confirmed family history: that pattern points away from Huntington's disease and towards a self-limiting cause such as Sydenham's chorea instead.

Huntington's disease is inherited in an autosomal dominant pattern, caused by a CAG-repeat expansion in the HTT gene (huntingtin), which was historically known by the alternate name IT15 before the gene itself was fully identified. Family history is therefore a key part of building a suggestive clinical picture, since an affected parent gives each child a 50% chance of inheriting the expanded gene. Sydenham's chorea is an important differential, particularly when family history is not confirmed: unlike Huntington's disease, it typically follows streptococcal infection, occurs in children or young adults, and is self-limiting rather than progressive and neurodegenerative. On EEG, Huntington's disease characteristically shows a low-voltage, flattened trace, distinct from other neurodegenerative or seizure-related EEG patterns.

• A 45-year-old man with a family history of a progressive movement and cognitive disorder shows marked caudate atrophy with disproportionate GABAergic medium spiny neuron loss on post-mortem.
• Questions on the CAG repeat expansion in the HTT gene on chromosome 4.
• Questions on earlier onset and greater severity across generations, particularly with paternal transmission (anticipation).
• Neuroimaging showing bilateral caudate atrophy with enlarged frontal horns of the lateral ventricles.

• Huntington's disease, autosomal dominant inheritance with a confirmatory family history, unlike Sydenham's chorea, which follows streptococcal infection without a hereditary pattern.
• Sydenham's chorea, self-limiting chorea in children or young adults following streptococcal infection, unlike Huntington's disease's progressive, neurodegenerative course.
• HTT gene (huntingtin), the CAG-repeat expansion gene causing Huntington's disease, historically known as IT15 before its identification.
• EEG in Huntington's disease, characteristically low-voltage and flattened, distinct from other neurodegenerative or seizure-related EEG patterns.

• Assuming any chorea-plus-dementia picture is automatically Huntington's disease without checking family history and genetic confirmation.
• Confusing Huntington's caudate/putamen (striatal) pathology with Parkinson's substantia nigraA deep brain structure rich in dopamine cells whose loss causes Parkinson's disease.Read more → pathology — opposite clinical phenotypes.
• Forgetting that late-stage Huntington's can show bradykinesia and rigidity (juvenile/Westphal variant), not just chorea — do not exclude the diagnosis just because movements have slowed.
• Mixing up the trinucleotide repeat diseases — CAG/HTT is Huntington's, CGG/FMR1 is fragile X, GAA/FXN is Friedreich's ataxiaLoss of full control of body movements, causing an unsteady, uncoordinated gait or actions.Read more →, CTG/DMPK is myotonic dystrophy.

• Localise the clue to the relevant anatomical level, cell type, pathway or molecular process.
• Map that structure or process to its normal function.
• Predict the deficit or clinical sign produced when it is disrupted.
• Reject options that belong to a neighbouring structure, pathway or level of explanation.