Huntington disease
Huntington disease is an autosomal dominant CAG trinucleotide repeat disorder of the huntingtin gene causing striatal and cortical neurodegeneration, presenting in mid-adulthood with a triad of chorea, cognitive decline, and psychiatric disturbance. Diagnosis is clinical plus confirmatory genetic testing; management is symptomatic, using VMAT2 inhibitors for chorea and psychiatric drug therapy, since no disease-modifying treatment exists.
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What this article covers
- Overview
Definition: Huntington disease is an autosomal dominant, progressive neurodegenerative disorder caused by an expanded CAG trinucleotide repeat in the huntingtin (HTT) gene on chromosome 4, producing…
- Epidemiology
Population prevalence: uncommon among neurodegenerative movement disorders, most prevalent in populations of Western European descent, with lower prevalence in East Asian populations.
- Risk factors
Family history of Huntington disease: the single dominant risk factor; each child of an affected parent has a 50% chance of inheriting the expanded allele.
- Pathophysiology
Genetic defect: an expanded, unstable CAG trinucleotide repeat in exon 1 of the HTT gene encodes an abnormally long polyglutamine tract in the huntingtin protein, producing a toxic gain of function…
- Clinical features
Motor (chorea): random, nonrepetitive, flowing, dance-like involuntary movements affecting the face, trunk, and limbs; patients often incorporate movements into voluntary gestures to mask them early in the disease.
- Differential diagnosis
Sydenham chorea: post-streptococcal autoimmune chorea in children, self-limited, associated with recent streptococcal infection and other features of rheumatic fever; lacks the autosomal dominant…
- Diagnosis
Diagnostic confirmation: genetic testing demonstrating a pathogenic CAG repeat expansion in the HTT gene (40 or more repeats is fully penetrant; 36-39 repeats shows reduced/incomplete penetrance…
- Management
First step: confirm the diagnosis and refer for genetic counseling before initiating symptomatic therapy; there is no disease-modifying treatment, so management is directed at the most functionally…
- Complications
Aspiration pneumonia: progressive dysphagia increases aspiration risk and is a leading cause of death in advanced disease.
- Prognosis
Course: relentlessly progressive over roughly 15 to 20 years from symptom onset to death; there is no cure and no treatment slows neurodegeneration.
- Prevention
No primary prevention exists because Huntington disease is a fully genetic, autosomal dominant disorder; there are no modifiable risk factors.
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