AKT · Child health/Genetic syndromeslow yield

Huntington disease

CAG trinucleotide repeat, HTT gene — autosomal dominant

Overview

An autosomal dominant neurodegenerative disorder from a CAG trinucleotide-repeat expansion in HTT, presenting in adulthood with chorea, cognitive decline and psychiatric change. Shows ANTICIPATION (earlier/worse over generations).

Recognise

Adult-onset (30s–50s) chorea (involuntary jerky movements)
Progressive cognitive decline/dementia
Psychiatric: depression, irritability, personality change; high suicide risk

Red flags

Suicide risk; juvenile (Westphal) variant with rigidity

Differentials & how to tell them apart

Sydenham choreapost-streptococcal, children, self-limiting

Wilson diseaseyoung, low caeruloplasmin, Kayser-Fleischer rings, liver disease — treatable

Drug-induced/other choreadrug history

Other dementiasno chorea/anticipation/family history

Investigations

Genetic testing (CAG repeat number in HTT) with genetic counselling. MRI: caudate (striatal) atrophy.

Management

1No disease-modifying treatment. Symptomatic: tetrabenazine for chorea; treat depression/psychosis; MDT and genetic counselling.
2Predictive testing offered with counselling; advance care planning; suicide-risk vigilance.

Tetrabenazine — symptomatic chorea

Antipsychotics/SSRIs — psychiatric and movement symptoms

Key points

Anticipation (earlier onset and more repeats down the generations, especially paternal transmission) is the classic genetics teaching point. Always exclude treatable Wilson disease in a young person with movement + psychiatric change.

Monitor & prognosis

Function, mood/suicide risk, swallowing, family.

Progressive; fatal over ~15–20 years.

Source: Clinical genetics; neurology