Huntington's disease: chorea, suicide risk, and the AU general practice approach

What Huntington’s disease is

Huntington’s disease (HD) is an autosomal-dominant progressive neurodegenerative disorder caused by an expansion of the CAG trinucleotide repeat in exon 1 of the HTT gene on chromosome 4p16.3. The expanded repeat encodes a mutant huntingtin protein with an abnormally long polyglutamine tract, which misfolds, aggregates, and drives progressive striatal medium-spiny neuron death over decades.

HD produces a triad of motor, cognitive, and neuropsychiatric features. The motor hallmark is chorea — involuntary, dance-like movements that initially appear as fidgeting and clumsiness and progress to marked involuntary limb and truncal movements, dysarthria, and dysphagia. Cognitive changes are frontostriatal in pattern: executive dysfunction and slowed processing precede episodic memory loss. Neuropsychiatric features — depression, anxiety, irritability, apathy, obsessive-compulsive symptoms, and psychosis — are often more disruptive to daily life than the motor symptoms, and may predate motor onset by years.

Australian prevalence is approximately 10–15 per 100,000 — consistent with other populations of European ancestry. Estimated 1,800–2,500 Australians are currently symptomatic, with a similar number of presymptomatic gene-positive carriers and approximately 10,000 at-risk first-degree relatives. HD Australia / Huntington’s Disease Network coordinates national services. Mean motor onset is aged 30–50 years; median survival is 15–20 years from motor onset.

The general practitioner’s role spans the full arc of HD: facilitating diagnosis, coordinating the multidisciplinary team, managing psychiatric and metabolic complications, monitoring suicide risk at every visit, supporting the family, and initiating advance care planning while capacity is preserved.

A. Core clinical — the AU general practice framework

Who to think about

Consider HD when:

• A patient presents with new involuntary movements (chorea, dystonia), unexplained depression or mood change, or cognitive difficulties — especially with a family history of chorea, “early dementia”, undiagnosed psychiatric illness, or suicide in the family
• A patient asks about testing because a parent, sibling, or child has been diagnosed
• A first-degree relative of a known HD patient reaches adulthood and wants to discuss risk

Family history may be obscured — HD frequently hides under labels such as “alcoholism”, “early dementia”, or “psychiatric illness” before the diagnosis was made. Take a detailed three-generation pedigree in any patient with new-onset chorea or unexplained executive dysfunction in midlife.

History

• Motor symptoms — involuntary fidgeting, restlessness, dropping things, gait changes, falls, slurred speech, choking on food
• Cognitive symptoms — slowed thinking, poor planning, difficulty multitasking, impaired insight
• Neuropsychiatric — new depression, anxiety, irritability, aggression, disinhibition, obsessive rituals, paranoid ideation, hallucinations; and critically — suicidal ideation
• Behavioural — sexual disinhibition, gambling, financial recklessness — often the most disruptive for families
• Sleep — insomnia, fragmented sleep, vivid dreams, REM sleep behaviour disorder
• Weight — HD is hypermetabolic; weight loss disproportionate to caloric intake is common and clinically significant
• Family history — first- and second-degree relatives; age of onset; any diagnosis of HD confirmed by gene testing

Examination

• Involuntary movements — observe for chorea (involuntary, flowing, purposeless movements), dystonia, motor impersistence (ask patient to extend tongue — it darts back involuntarily; grip your fingers then note the “milkmaid” grip pattern)
• Oculomotor — slowed saccade initiation is an early sign; ask the patient to look rapidly from side to side
• Gait — choreiform gait lurches; retropulsion pull test
• Cognitive screen — verbal fluency, symbol digit, MoCA; cognitive impairment is frontostriatal (executive dysfunction before memory loss)
• Psychiatric — Columbia Suicide Severity Rating Scale (C-SSRS) at every visit; PHQ-9 quarterly; collateral from a family member is invaluable and often essential

Investigations

• HTT CAG-repeat sizing — the definitive test. For a symptomatic patient: MBS item 73296 (heritable mutation testing); specialist- or clinical-genetics-initiated.
• For an asymptomatic at-risk relative: MBS item 73297 (cascade testing); requires the mandatory multidisciplinary pre-test counselling pathway — see Section C. Never order this in general practice without that pathway in place.
• MRI brain: MBS item 63551 — caudate and putamen atrophy (widened frontal horn); volumetric loss can precede motor onset by 10–15 years
• Exclude mimics where HTT is not yet confirmed: TFTs, B12, folate, copper and caeruloplasmin (Wilson disease), HIV, syphilis serology, ANA (lupus chorea), peripheral blood film for acanthocytes (neuroacanthocytosis)

CAG repeat interpretation

CAG repeat	Classification	Implication
26 or fewer	Normal	No risk to self or offspring
27–35	Intermediate / grey zone	No clinical HD; small offspring risk with paternal transmission
36–39	Reduced penetrance	May or may not develop HD in normal lifespan
40 or more	Full penetrance	Will develop HD; offspring 50% risk
60 or more	Typically juvenile onset	Often paternal transmission with anticipation

B. Pharmacological management

Chorea

Treat chorea only when it causes functional impairment, falls, weight loss, or significant social distress — mild chorea alone does not necessarily require treatment.

VMAT2 inhibitors — first-line (all PBS Authority Streamlined for HD chorea):

Per Therapeutic Guidelines and Australian Medicines Handbook:

• Tetrabenazine (Xenazine): start 12.5 mg once daily in the morning, titrate by 12.5 mg weekly to effect; usual maintenance 25 mg three times daily (maximum 100 mg/day). CYP2D6 poor metabolisers — halve the dose. Regulatory warning for depression and suicidality — screen and treat depression before initiating; monitor mood throughout. The TETRA-HD RCT (Neurology 2006) confirmed significant chorea reduction versus placebo.
• Deutetrabenazine (Austedo): deuterated tetrabenazine with longer half-life and twice-daily dosing, reducing peak-related adverse effects. Start 6 mg once daily in the morning, titrate by 6 mg weekly; usual maintenance 12–24 mg twice daily (maximum 48 mg/day). FIRST-HD RCT (JAMA 2016) confirmed chorea reduction with better tolerability than tetrabenazine. PBS Authority Streamlined since 2020.
• Valbenazine (Ingrezza): selective VMAT2 inhibitor, once-daily dosing, PBS Authority Streamlined for HD chorea. Useful in patients intolerant of twice or three-times-daily dosing.

All three VMAT2 inhibitors carry the depression/suicidality warning. Common side effects: sedation, parkinsonism, akathisia. Avoid haloperidol long-term — carries high risk of tardive dyskinesia and cognitive worsening in this population.

Antipsychotics — second-line or where dual benefit is needed:

• Olanzapine 2.5–15 mg at night: chorea plus agitation or insomnia; weight gain is often beneficial given HD hypermetabolism
• Risperidone 0.5–4 mg/day: alternative where olanzapine sedation is limiting
• Aripiprazole: partial agonist; metabolically friendlier

Neuropsychiatric management

Depression (30–50% lifetime prevalence in HD) — SSRI first-line: sertraline 50–200 mg, citalopram 20–40 mg, escitalopram 10–20 mg. Mirtazapine 15–45 mg is useful when insomnia and weight loss are prominent. Avoid tricyclics in patients with cognitive impairment or falls risk.

Suicidality — HD carries a suicide rate 4–7× the general population, with two peaks: around diagnosis, and at the transition to significant functional dependency (Paulsen JNNP 2005). Use the Columbia Suicide Severity Rating Scale at every clinical contact. Document a safety plan, review means restriction (firearms, stockpiled medications, vehicle access), involve family carers, and maintain low threshold for psychiatric referral.

Irritability and aggression — SSRI first-line; atypical antipsychotic second-line; mood stabiliser (valproate, lamotrigine) in refractory cases.

Anxiety — SSRI; mindfulness-based approaches adapted for cognitive limitations.

Apathy — distinguish carefully from depression; bupropion off-label; structured daily activity.

Sleep — melatonin 2–10 mg at night; clonazepam 0.5–1 mg for confirmed REM sleep behaviour disorder. Avoid benzodiazepines as routine hypnotics — cumulative cognitive harm in a cognitively impaired population.

Nutritional and supportive management

HD is hypermetabolic — caloric requirements are approximately 120% of predicted basal needs. Refer to a dietitian early and review weight at every visit. Speech pathology every 6–12 months for swallow assessment; modified diet and augmentative communication devices in later stages. Physiotherapy for gait, balance, and falls prevention; occupational therapy for home modifications, assistive technology, and NDIS planning; social work for Centrelink, NDIS, and advance care planning.

C. Predictive testing and genetic counselling

The multidisciplinary predictive-testing pathway for asymptomatic at-risk relatives is a safeguard. It is mandatory — not optional — by international guideline (MacLeod Clin Genet 2013), HDSA 2016, and RACGP Genomics 2024. Never order an HTT gene test for a healthy relative without this pathway in place. Doing so can cause profound psychological harm, including completed suicide.

Referral pathway:

Refer to a state HD service or clinical-genetics unit. The pathway includes: two pre-test counselling sessions (clinical geneticist, genetic counsellor, neurologist, psychologist); a mandatory suicide risk screen before testing; partner and family involvement; result disclosure in person with a support person; and structured follow-up at one week and one month.

Predictive testing is not offered to minors except in compelling clinical circumstances (e.g., juvenile-onset symptoms).

Reproductive options after predictive testing: preimplantation genetic diagnosis via IVF (Medicare-rebated under a specialist), prenatal testing, or exclusion testing (the at-risk parent does not learn their own status). Refer to a reproductive-medicine specialist.

Insurance moratorium:

Counsel all patients considering predictive testing about the FSC Standard No. 11A life-insurance moratorium (2019, extended 2024): insurers cannot adversely use predictive HD gene test results for life insurance up to AUD $500,000 death cover, AUD $500,000 total and permanent disability, AUD $200,000 trauma, and AUD $96,000 per year income protection. Patients should consider securing cover above the moratorium limits before testing, if relevant.

D. Australian operations — PBS, MBS, NDIS

PBS items for HD:

• Tetrabenazine — Authority Required Streamlined for chorea in Huntington’s disease
• Deutetrabenazine (Austedo) — Authority Required Streamlined for HD chorea (listed 2020)
• Valbenazine (Ingrezza) — Authority Required Streamlined for HD chorea (listed 2024)
• SSRIs, olanzapine, risperidone, aripiprazole — PBS general schedule (Authority Required for some indications)

MBS items:

• HTT gene test (diagnostic, symptomatic patient): MBS 73296
• HTT gene test (predictive cascade, asymptomatic relative with known familial mutation): MBS 73297
• MRI brain: MBS 63551
• GPCCMP preparation: MBS 965 / review MBS 967 (HD is a textbook GPCCMP indication)
• Mental Health Care Plan: MBS 2715/2717 — routine at HD diagnosis given 30–50% depression prevalence
• Allied health under GPCCMP: speech pathology 10970, dietitian 10954, physiotherapy 10960

NDIS:

HD is on the NDIS List A of conditions where permanent and significant disability is presumed once symptomatic — this means fast-tracked NDIS access without requiring extensive functional assessment. Pre-symptomatic gene-positive individuals are not eligible. Supports include physiotherapy, occupational therapy, speech pathology, dietitian, psychology, assistive technology, home modifications, and daily living support.

HD Australia:

HD Australia / Huntington’s Disease Network provides national coordination, peer support, state services navigation, and links to the Enroll-HD global observational study (Australian sites participate; patients can enrol and access trial information).

E. Special populations

Children of affected parents who are themselves young adults. Reaching adulthood with an HD parent creates the question of predictive testing. Support the person without pressure in either direction — some want to know; many do not. Neither is wrong. The GP’s role is to offer referral to the multidisciplinary pathway when the person is ready, and to monitor for early symptoms regardless of testing status. Discuss the insurance moratorium before any testing decision.

Juvenile HD (onset under 20 years). Presents as a rigid-akinetic-parkinsonian phenotype rather than the classic choreiform pattern; may include seizures and rapid cognitive decline. Nearly always paternal transmission with CAG anticipation (greater than 60 repeats typical). This phenotype is frequently misdiagnosed initially. Refer urgently to paediatric neurology and clinical genetics.

Advanced HD. When total functional capacity falls to 4 or below, initiate or advance palliative care referral. Advance care planning — EPOA, advance care directive, preferred place of care, PEG and ventilation preferences — should be completed while the patient still has capacity. Voluntary assisted dying is available in all Australian states and the Northern Territory (as of 2026) — HD with prognosis of 12 months or fewer typically meets medical eligibility criteria; refer to state VAD services for individual assessment.

When to escalate

Refer urgently to the emergency department or psychiatry:

• Active suicidal ideation with plan or intent
• Psychosis with risk to self or others
• Acute aspiration or choking event
• Falls with significant injury

Refer routinely to:

• Neurology (movement disorders) — at diagnosis and annually; sooner if VMAT2 inhibitor titration needed
• Clinical genetics — at diagnosis (to confirm, counsel family, discuss predictive testing)
• Psychiatry — annually; sooner for refractory depression, new psychosis, or active suicidality
• HD specialist services — HD Australia can assist with state-based service navigation

What this article is and is not

This is general health information synthesised from Therapeutic Guidelines, Australian Medicines Handbook, RACGP Genomics in General Practice 2024, HDSA clinical guidelines, and peer-reviewed HD literature. It is not personal medical advice and does not create a doctor–patient relationship. Predictive genetic testing, chorea management, and neuropsychiatric care are specialist-directed.

For Australian consumer information: HD Australia, HealthDirect — Huntington’s disease, Better Health Channel, Enroll-HD.

For acute mental-health crisis: Lifeline 13 11 14, Beyond Blue 1300 22 4636, Suicide Call Back Service 1300 659 467.

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Sources cited

1. Therapeutic Guidelines (eTG) — Neurology and Psychotropic
2. Australian Medicines Handbook
3. RACGP — Genomics in General Practice (2024)
4. Bates GP et al. — Huntington disease (Nat Rev Dis Primers 2015)
5. Huntington Study Group — TETRA-HD (Neurology 2006)
6. Frank S et al. — FIRST-HD (JAMA 2016)
7. Paulsen JS et al. — Critical periods of suicide risk in HD (JNNP 2005)
8. MacLeod R et al. — Recommendations for predictive genetic testing in HD (Clin Genet 2013)
9. HDSA — Physician’s Guide to Huntington’s Disease (2016, updated 2022)
10. FSC Standard No. 11A — Life Insurance Moratorium on Genetic Tests
11. HD Australia / Huntington’s Disease Network
12. HealthDirect — Huntington’s disease
13. Better Health Channel — Huntington’s disease
14. Enroll-HD — global HD observational study
15. NDIS Operational Guidelines — List A conditions
16. Lifeline
17. Beyond Blue