Huntington's Disease Diagnosis: Symptoms, Testing & What to Expect

Diagnostic Pathway

Clinical Suspicion: Adult-onset (30s–50s) chorea + psychiatric/cognitive decline + family history.
Genetic Testing (Gold Standard): CAG repeat expansion in HTT gene (chr4p16.3).
- Normal: ≤26 repeats.
- Intermediate: 27–35 (not affected, but expansion risk in offspring).
- Reduced Penetrance: 36–39 (may or may not develop).
- Full Penetrance: ≥40 (will develop if live long enough).
Predictive Testing Protocol: For at-risk asymptomatic adults: pre-test counseling (genetic, psychological), informed consent, neurologic exam, blood draw, results disclosure in person, post-test support. Minors not tested.
Neurological Exam: Motor (UHDRS-TMS: chorea, dystonia, bradykinesia, gait), cognitive (executive, memory), psychiatric (depression, irritability, apathy, psychosis).
Neuroimaging: MRI: caudate/putamen atrophy (early), global atrophy (late). Not diagnostic alone.
Psychiatric Evaluation: High suicide risk; treat depression, anxiety, OCD, psychosis.

Neurology, psychiatry, genetics, PT/OT/SLP, social work, palliative care.
Tetrabenazine, deutetrabenazine, valbenazine for chorea; SSRIs, antipsychotics for mood/psychosis.
Clinical trials: HTT-lowering (ASOs, RNAi), PDE10 inhibitors.