Huntington disease
CAG trinucleotide-repeat expansion in HTT (autosomal dominant, chr 4)
Overview
An autosomal-dominant trinucleotide (CAG) repeat disorder causing progressive chorea, cognitive decline and psychiatric disturbance, with onset usually in mid-adulthood. Shows ANTICIPATION (earlier/worse with successive generations). No cure — management is supportive.
Recognise
- Chorea (jerky, purposeless movements) + later dystonia/bradykinesia
- Progressive cognitive decline (executive) and psychiatric features (depression, irritability, psychosis); high suicide risk
- Family history (autosomal dominant); onset typically 30s–50s; anticipation
Red flags
- Suicide risk; the genetic/reproductive implications for relatives (predictive testing + counselling)
Differentials & how to tell them apart
Investigations
Genetic testing (CAG repeat number in HTT) is diagnostic; MRI may show caudate (striatal) atrophy; involve genetic counselling.
Management
Supportive MDT care; tetrabenazine for chorea; treat psychiatric symptoms
- 1Multidisciplinary supportive care; tetrabenazine for disabling chorea; manage depression/psychosis and suicide risk.Gate: Predictive genetic testing must be preceded by genetic counselling (autosomal dominant, anticipation, profound implications for relatives and reproduction)
- 2Long-term: SALT/dietitian, OT, advance care planning; family cascade counselling.
Key points
Chorea + dementia + psychiatric change + dominant family history = Huntington; anticipation explains earlier onset down the generations. Care is supportive and family-centred.
Monitor & prognosis
Motor, cognitive, psychiatric symptoms and suicide risk; family support.
Progressive over ~15–20 years to death; no disease-modifying therapy.
Source: Clinical genetics; neurology