[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Central nervous system](https://durgical.com/en/general-pathology/areas/cns/) › Huntington disease and inherited ataxias

# 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.

Updated Nov 12, 2026

## Key points

- Huntington: caudate atrophy with enlarged frontal horns; loss of medium spiny GABAergic neurons; intranuclear huntingtin inclusions.
- Anticipation: larger repeats give earlier onset, and the repeat expands mostly through the father.
- Spinocerebellar ataxias: dominant, many CAG repeats (SCA1, 2, 3, 6, 7, 17); cerebellar and brainstem degeneration.
- Friedreich ataxia: recessive GAA expansion in FXN, mitochondrial iron overload; ataxia, lost position sense, areflexia, hypertrophic cardiomyopathy, diabetes and pes cavus.
- Ataxia-telangiectasia: recessive ATM mutation; cerebellar ataxia in childhood, eye and skin telangiectasias, immunodeficiency, radiation sensitivity and lymphomas.

## 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](https://durgical.com/en/conditions/huntington-disease/) | HTT, CAG | Autosomal dominant | Caudate and putamen neuron loss |
| [Spinocerebellar ataxias](https://durgical.com/en/conditions/spinocerebellar-ataxias/) | Several genes, many CAG | Autosomal dominant | Cerebellar, brainstem and cord degeneration |
| [Friedreich ataxia](https://durgical.com/en/conditions/friedreich-ataxia/) | FXN, GAA (intron) | Autosomal recessive | Dorsal root ganglia, dorsal columns, spinocerebellar tracts, heart |
| [Ataxia-telangiectasia](https://durgical.com/en/conditions/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.

## Memory aid

CAG means glutamine: the more you repeat, the earlier you dance (chorea) and the sooner the caudate shrinks.

## 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.

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## Elsewhere in DurgiPedia

- [Basal ganglia and movement control](https://durgical.com/en/physiology/basal-ganglia-and-movement-control/)
- [Functions of the cerebellum](https://durgical.com/en/physiology/functions-of-the-cerebellum/)
- [Cerebellar syndrome](https://durgical.com/en/clinical-exam/cerebellar-syndrome/)
- [Cerebellar tests: finger–nose, heel–shin and rapid alternating movements](https://durgical.com/en/clinical-exam/cerebellar-tests-finger-nose-heel-shin-and-rapid-alternating-movements/)

## Connections

## Related 4

- [Neurodegeneration: the protein table](https://durgical.com/en/general-pathology/neurodegeneration-the-protein-table/)
- [Motor neuron diseases](https://durgical.com/en/general-pathology/motor-neuron-diseases/)
- [Nonclassic inheritance: repeat expansions, mitochondrial genes, imprinting, mosaicism](https://durgical.com/en/general-pathology/nonclassic-inheritance-repeat-expansions-mitochondrial-genes-imprinting-mosaicis/)
- [Genomic instability: mismatch repair, BRCA and xeroderma pigmentosum](https://durgical.com/en/general-pathology/genomic-instability-mismatch-repair-brca-and-xeroderma-pigmentosum/)

## Related conditions 5

- [Huntington disease](https://durgical.com/en/conditions/huntington-disease/)
- [Spinocerebellar ataxias (autosomal dominant ataxias)](https://durgical.com/en/conditions/spinocerebellar-ataxias/)
- [Friedreich ataxia](https://durgical.com/en/conditions/friedreich-ataxia/)
- [Ataxia-telangiectasia](https://durgical.com/en/conditions/ataxia-telangiectasia/)
- [Hypertrophic cardiomyopathy](https://durgical.com/en/conditions/hypertrophic-cardiomyopathy/)

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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](https://medlineplus.gov/genetics/condition/huntingtons-disease/) (MedlinePlus, US National Library of Medicine, 2026); [Ataxia-telangiectasia: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/ataxia-telangiectasia/) (MedlinePlus, US National Library of Medicine, 2026).

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Representative model, for educational purposes only.

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License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/huntington-disease-and-inherited-ataxias/