Chorea and Huntington disease

01OverviewDefinition, clinical context and the essential points that orientate the chapter.

Chorea is a descriptive sign produced by disrupted motor network control, particularly basal ganglia circuitry. At the bedside, observe the person at rest, during posture, speech, walking and a cognitive task; chorea often increases with distraction. Ask whether movements are suppressible, preceded by an urge, patterned or rhythmic. Dystonia creates sustained twisting postures, myoclonus produces lightning-like jerks and tics are stereotyped and temporarily suppressible. Chorea can be asymmetric after a structural lesion or generalised in genetic, metabolic, autoimmune and drug-related disease.

Huntington disease typically evolves across motor, cognitive and behavioural domains. Early eye-movement abnormalities, clumsiness and chorea can progress towards dysarthria, dysphagia, dystonia, bradykinesia and rigidity. Executive slowing and impaired judgement can affect work or money before a global cognitive score changes. Depression, apathy, anxiety, irritability, obsessive behaviour, psychosis and suicide risk require active assessment. Juvenile disease more often presents with rigidity, bradykinesia, cognitive decline and seizures than florid chorea.

Genetic confirmation requires informed consent because the result has implications for relatives, reproduction, insurance and psychological wellbeing. A negative family history does not completely exclude the diagnosis because history may be unknown, relatives may have died young, parentage may differ or a new expansion may emerge. Testing, disclosure to relatives and symptomatic prescribing require specialist neurology, clinical genetics, mental-health input and local governance.

Key points

Chorea consists of brief, irregular, non-rhythmic movements that flow unpredictably between body regions and become incorporated into apparently purposeful activity; it differs from rhythmic tremor and stereotyped tics.
Look for motor impersistence such as an unsustained tongue protrusion or fluctuating milkmaid grip, unpredictable facial movements, fidgeting gait and intrusive distal movements during posture.
Huntington disease is an autosomal dominant neurodegenerative disorder caused by a CAG repeat expansion in HTT; each child of an affected person has a one-in-two chance of inheriting the expansion.
Motor, executive-cognitive and psychiatric change often overlap. Irritability, apathy, depression, impulsivity or loss of planning may precede obvious chorea and require direct collateral history.
Chorea is not synonymous with Huntington disease: medicines, hyperthyroidism, autoimmune disease, antiphospholipid syndrome, Sydenham chorea, pregnancy, stroke, Wilson disease and metabolic or toxic states are important alternatives.
Diagnostic testing in a symptomatic adult and predictive testing in a well person have different consent pathways; presymptomatic testing belongs in clinical genetics with staged counselling and psychological support.
Tetrabenazine or an antipsychotic may reduce disabling chorea but can worsen depression, parkinsonism, akathisia, swallowing or sedation; treatment targets function and comfort rather than movement visibility alone.
Weight loss, dysphagia, aspiration, falls, driving, capacity, finances and family support become as important as movement severity, making coordinated multidisciplinary follow-up essential.
No current routine treatment stops progression, so realistic planning, advance care discussions and support for relatives should begin early while preserving autonomy and hope.

02AetiologyUnderlying causes, associations and risk factors, with why each one matters.

Huntington disease

An expanded CAG repeat in HTT causes autosomal-dominant neurodegeneration, with motor, cognitive and psychiatric manifestations and important implications for biological relatives.

Medicine and metabolic causes

Dopamine-active medicines, hyperthyroidism, glucose disturbance, liver disease and toxins can produce acquired chorea, often with a clear exposure or systemic context.

Immune and infectious disease

Sydenham chorea, systemic lupus, antiphospholipid syndrome and selected infections can disrupt basal-ganglia function, particularly with systemic or inflammatory features.

Structural and genetic alternatives

Stroke, tumour, Wilson disease and other inherited movement disorders should be considered when onset, age, symmetry or associated signs do not fit Huntington disease.

03PathophysiologyThe causal sequence from the underlying abnormality to symptoms and harm.

1
Striatal circuit disruption
Disease alters inhibitory medium-spiny neuron function within basal-ganglia loops that normally select desired movement and suppress competing motor programmes.
2
Motor disinhibition
Reduced indirect-pathway output permits unwanted, brief and irregular muscle activation to flow unpredictably between body regions.
3
Network degeneration
In Huntington disease, continuing striatal and cortical neuronal loss extends dysfunction from movement circuits into executive, emotional and behavioural networks.

04Clinical features and red flagsSymptoms, examination findings, patterns of presentation and time-critical warnings.

Generalised chorea

Irregular flowing movements affecting face, trunk and limbs, with movement camouflage and motor impersistence, support a choreic syndrome after anxiety, restlessness and tics have been separated.

Huntington phenotype

Progressive chorea or clumsiness plus executive, personality or mood change in an adult with compatible family history should prompt a Huntington-experienced neurological and genetic assessment.

Acquired hemichoreaRed flag

Abrupt unilateral chorea suggests a contralateral basal ganglia or subthalamic lesion, severe non-ketotic hyperglycaemia or another focal process and needs urgent imaging and metabolic assessment.

Medication-related movement

Levodopa, dopamine agonists, stimulants and tardive syndromes after dopamine-receptor blocking drugs can produce choreiform or dyskinetic movements; timing and phenomenology are decisive.

Psychiatric and safeguarding riskRed flag

Suicidal thinking, impulsive risk, aggression, self-neglect or loss of financial judgement may be disease manifestations and require immediate proportionate safety assessment.

05InvestigationsWhat to request, why it matters and how to interpret it.

Investigation order

Read from the initial assessment onwards. Tests may run in parallel in urgent care; first-line, preferred, confirmatory, definitive and gold-standard labels appear only when the chapter explicitly states them.

01
Phenomenology and collateral historyFirst step
Why
Confirm chorea, map progression and identify cognitive, psychiatric, medicine and family clues.
Interpretation and limitations
Video with consent can support movement-disorder review. A relative’s account may expose executive or behavioural decline but must be balanced with the person’s own perspective and privacy.
02
Targeted acquired-cause screen
Why
Find reversible or urgent alternatives before assuming a primary neurodegenerative disorder.
Interpretation and limitations
Select glucose, electrolytes, renal and liver function, thyroid tests, blood count, inflammatory or autoimmune studies, infection tests and toxicology from age, tempo and systemic features; broad untargeted panels create false leads.
03
MRI brain
Why
Assess sudden, asymmetric, atypical or rapidly progressive chorea and structural differential diagnoses.
Interpretation and limitations
Caudate atrophy can support established Huntington disease but is neither required nor sufficiently specific for predictive diagnosis. Focal basal ganglia lesions redirect the cause pathway.
04
HTT CAG repeat testing
Why
Confirm the molecular diagnosis when a symptomatic person has a compatible phenotype or perform predictive testing through genetics.
Interpretation and limitations
Repeat size and penetrance require specialist explanation; the number does not precisely predict an individual’s onset or course, and presymptomatic testing must remain voluntary.
05
Functional, swallowing and neuropsychiatric assessment
Why
Measure consequences that determine care, safety and treatment priorities.
Interpretation and limitations
Review weight, speech, swallowing, falls, daily activities, mood, behaviour, cognition, capacity and carer strain. Chorea amplitude alone is a poor proxy for total disease burden.

06Differential diagnosisRealistic alternatives and the features that help distinguish them.

Tics

Stereotyped recurrent movements with a premonitory urge and temporary suppressibility favour tics, whereas chorea flows irregularly and lacks a consistent repeated form.

Dystonia

Sustained patterned twisting postures, directional pull and sensory tricks support dystonia rather than the brief, random fragments of chorea.

Akathisia

Subjective inner restlessness with purposeful pacing after dopamine blockade suggests akathisia; chorea remains involuntary and irregular even when the person is seated.

Myoclonus

Lightning-like synchronous jerks are briefer and more shock-like than flowing chorea and may show stimulus sensitivity or an EEG correlate.

07ManagementImmediate care, first-line treatment, alternatives and escalation.

01New choreaDefine tempo and reversible causeFirst stepIrregular involuntary movements are newly observed or rapidly worsening.

11. Confirm choreic phenomenology, establish sudden versus progressive onset, examine focal neurology and assess cognition, behaviour, temperature and swallowing safety.
22. Reconcile prescription, antiemetic, psychiatric, dopaminergic and recreational exposures with the movement timeline, including recently stopped agents.
33. Order urgent imaging and metabolic or inflammatory testing when onset is acute, unilateral or encephalopathic, treating the identified systemic cause in parallel.
44. Refer progressive unexplained chorea to a movement-disorder service and avoid disclosing an inherited diagnosis before appropriate consent and evidence.

02Suspected HuntingtonConfirm without bypassing consentThe phenotype and family context make Huntington disease a credible diagnosis.

11. Discuss what diagnostic testing can and cannot answer, its implications for relatives and the person’s preference about receiving a genetic result.
22. Refer to Huntington-experienced neurology and clinical genetics, arranging mental health support and a private opportunity to decide without family coercion.
33. Use consented HTT testing in the symptomatic pathway and reserve predictive testing of an unaffected adult for the staged genetics programme.
44. After confirmation, communicate the result directly, assess immediate psychological safety and arrange a named multidisciplinary contact rather than ending care at diagnosis.

03Living with diseaseTreat burdens and plan aheadHuntington disease is diagnosed or a progressive choreic disorder requires continuing support.

11. Agree whether movement, mood, psychosis, sleep, pain or cognition is the present treatment priority and select one intervention with measurable outcomes.
22. Refer early for speech and language therapy, dietetics, physiotherapy and occupational assessment, including texture, calorie, falls and equipment plans.
33. Review driving, work, benefits, capacity, advance care, reproductive options and support for relatives at a pace the person can tolerate.
44. Reassess treatment burden as disease changes, deprescribing medicines that worsen swallowing, rigidity, falls or quality of life without continuing benefit.

Key medicines and prescribing safety2 treatments · regimens, roles and cautions

Depletes presynaptic monoamines through VMAT2 inhibition and can reduce functionally disruptive chorea in Huntington disease.

Tetrabenazine

A movement-disorder specialist starts a low daily dose and titrates in small divided increments to the lowest effective regimen, following the current BNF and product maximum rather than a fixed target.

Screen and monitor depression, suicidality, parkinsonism, akathisia, sedation, dysphagia and QT or interaction risk. Benefit for visible movement must outweigh worsening of mood, gait and voluntary function.

Can address psychosis or behavioural danger and may also suppress chorea when these targets coexist.

Specialist-selected antipsychotic

Use the lowest effective oral dose with slow titration when psychosis, severe irritability or chorea provides a documented indication; medicine and schedule depend on metabolic and motor risk.

Discuss sedation, metabolic effects, orthostasis, QT prolongation, swallowing, parkinsonism, akathisia and tardive syndromes. Do not use solely to make movements less noticeable to observers.

08ComplicationsImportant consequences, why they occur and why they matter clinically.

Falls, dysphagia and weight loss

Movement disorder, impaired judgement and progressive swallowing dysfunction cause injuries, aspiration and negative energy balance despite increased nutritional support.

Psychiatric crisis

Depression, irritability, impulsivity and psychosis can cause relationship breakdown, self-harm or suicide risk and may precede obvious chorea.

Cognitive and capacity decline

Executive dysfunction progressively impairs finances, driving, employment and complex decisions, requiring supported decision-making and safeguarding review.

Family and genetic impact

Predictive uncertainty, reproductive decisions and risk to relatives create psychological and ethical consequences extending beyond the affected person.

09Monitoring and follow-upTreatment response, safety checks and longer-term review.

Review depression, hopelessness, impulsivity, psychosis and suicide risk directly, especially near diagnosis, functional loss and medicine changes.
Track weight, meal duration, coughing, voice change, hydration and chest infections, with early swallowing and dietetic reassessment before crisis develops.
Measure movement treatment against walking, eating, sleep, pain or care goals while watching for rigidity, akathisia, sedation and falls.
Repeat cognition, capacity and daily-function review in context, because financial, medication and driving decisions can become unsafe before severe memory loss appears.
Check carer burden, safeguarding, advance planning and access to the Huntington multidisciplinary team at each major transition.

10Special situationsVariants, exceptions and circumstances that change the usual approach.

Chorea can be hidden

People often convert an involuntary movement into a scratch, gesture or step, so observation during posture and distraction reveals more than stillness on command.

Motor impersistence helps

Inability to sustain tongue protrusion, eye closure or a steady grip reflects impaired maintenance of voluntary contraction and supports a choreic syndrome.

Family history can mislead

Apparent absence may reflect small families, early death, misdiagnosed psychiatric illness, non-disclosure or unknown parentage rather than absence of an inherited expansion.

Testing choices belong to adults

An at-risk well adult may choose predictive testing or choose uncertainty; relatives’ desire to know does not override that person’s autonomous decision.

Late disease may look akinetic

Chorea can diminish as bradykinesia, rigidity and dystonia dominate, so reduced involuntary movement does not necessarily signal neurological improvement.

11Common pitfallsFrequent interpretation and management errors.

01
Equating fidgeting with anxiety can delay recognition of progressive chorea, while labelling every restless movement Huntington disease ignores common acquired causes.
02
Ordering predictive HTT testing through a routine blood form without genetics counselling bypasses consent, psychological preparation and family implications.
03
Treating visible chorea aggressively despite worsened swallowing, balance or depression prioritises observer comfort over the patient’s function.
04
Assuming cognitive screening is normal because memory recall is preserved overlooks early executive dysfunction, impulsivity and impaired judgement.
05
Failing to ask directly about suicide risk in a progressive inherited disorder misses a treatable and time-critical component of care.