Huntington disease and inherited ataxias
- Lesion
Huntington disease destroys the caudate and causes chorea and dementia; inherited ataxias wear out the cerebellum, cord and nerves.
What it is
Huntington disease is an autosomal dominant disorder caused by an expanded CAG repeat in the HTT gene, which adds a long polyglutamine stretch to huntingtin. Medium spiny neurons of the caudate and putamen die, causing chorea, psychiatric change and dementia. The spinocerebellar degenerations are a broader group: dominant spinocerebellar ataxias (many also polyglutamine diseases), recessive Friedreich ataxia (a GAA repeat in FXN that lowers frataxin) and ataxia-telangiectasia (ATM mutations with DNA repair failure).
Step by step
- An expanded CAG repeat adds a long polyglutamine tract to huntingtin.
- The mutant protein misfolds, enters the nucleus and disturbs transcription.
- Striatal medium spiny neurons, rich in glutamate input, die first.
- The indirect basal ganglia pathway fails, releasing involuntary movements (chorea).
- Cortical loss adds dementia; psychiatric symptoms are frequent.
Huntington disease and the main inherited ataxias
| Disease | Gene and repeat | Inheritance | Main pathology |
|---|---|---|---|
| Huntington disease | HTT, CAG | Autosomal dominant | Caudate and putamen neuron loss |
| Spinocerebellar ataxias | Several genes, many CAG | Autosomal dominant | Cerebellar, brainstem and cord degeneration |
| Friedreich ataxia | FXN, GAA (intron) | Autosomal recessive | Dorsal root ganglia, dorsal columns, spinocerebellar tracts, heart |
| Ataxia-telangiectasia | ATM point mutations | Autosomal recessive | Purkinje and granule cell loss, telangiectasias |
Clinical notes
- Huntington disease usually starts in mid-adult life; predictive genetic testing needs careful counselling.
- A large Huntington disease family cluster in Venezuela was key to finding the gene.
Test yourself
Think of the answer, then tap the question to see it.
Which brain structure atrophies most in Huntington disease?
The caudate nucleus (and putamen), with enlargement of the frontal horns of the lateral ventricles.
What is anticipation in Huntington disease?
Earlier onset in successive generations because the CAG repeat tends to expand, especially when inherited from the father.
Which repeat and gene cause Friedreich ataxia?
A GAA repeat expansion in an intron of FXN, which reduces frataxin, a mitochondrial iron-handling protein.
Elsewhere in DurgiPedia
- Basal ganglia and movement control
- Functions of the cerebellum
- Cerebellar syndrome
- Cerebellar tests: finger–nose, heel–shin and rapid alternating movements
Connections
Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.
Sources: Huntington's disease: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Ataxia-telangiectasia: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.