Medical Genetics

Huntington's disease

An autosomal-dominant neurodegenerative disorder caused by a CAG-repeat expansion in HTT, producing progressive motor, cognitive and psychiatric change; diagnosis and predictive testing require specialist genetics support and treatment is symptomatic and multidisciplinary.

In a nutshell

Huntington's disease is an autosomal-dominant HTT CAG-repeat expansion causing progressive motor, cognitive and psychiatric change. Repeat categories matter: 36–39 repeats have reduced penetrance and 40 or more has a definite lifetime risk, but repeat length does not predict an exact onset. Diagnose symptomatic disease through neurology and genetics; predictive testing is a voluntary structured adult pathway. Treat functionally troublesome chorea cautiously, assess suicide risk actively, and use multidisciplinary swallowing, nutrition, therapy, social-care and advance-care support.

Classic presentation

An adult with a parent affected by Huntington's disease develops subtle executive or behavioural change, depression or irritability, then chorea and clumsiness. The diagnosis is clinical plus HTT repeat testing; assess suicide risk, cognition, swallowing, weight and capacity from the outset.

Key points

HTT CAG-repeat expansion is autosomal dominant; each child of a parent with a full expansion has a 50% chance of inheriting it.
36–39 repeats have reduced penetrance; 40 or more is associated with a definite lifetime risk. Repeat length does not give an exact age of onset.
Paternal transmission is more prone to repeat expansion and anticipation, but it does not allow precise prediction for an individual.
Motor, cognitive and psychiatric symptoms form one disease; depression, irritability, psychosis, apathy and suicide risk require active assessment.
Predictive testing is voluntary, usually for adults, and should occur through a clinical-genetics protocol with pre-test counselling and follow-up.
Treat chorea only when it is functionally or psychologically troublesome, balancing tetrabenazine or antipsychotic adverse effects against benefit.
Early speech and language, dietetic, physiotherapy, occupational, social-care, palliative and carer support reduce avoidable harm.

First-line investigation

Neurology and clinical-genetics assessment with diagnostic HTT CAG-repeat testing; use MRI and targeted tests for mimics or complications rather than as a substitute for the clinical and genetic pathway.

Management

Assess safety and reversible deterioration

Ask directly about suicidal thoughts, psychosis, severe impulsivity, aggression, self-neglect, choking, aspiration, dehydration and rapid weight loss; use urgent mental-health, medical or speech-and-language escalation when safety is compromised.^4,5,12

Confirm and coordinate

Refer suspected or confirmed disease to neurology or a specialist Huntington's service and clinical genetics; coordinate the person-centred MDT from early disease rather than waiting for advanced disability.^3,2,6
Offer diagnostic testing with informed consent, and offer predictive testing only through the structured adult genetics pathway with counselling and follow-up.^1,3

Treat symptoms without causing harm

Treat chorea only when it causes meaningful distress, injury or functional impairment; specialist prescribers should balance tetrabenazine or antipsychotic benefit against depression, cognition, rigidity, swallowing, falls and drug interactions.^7,8
Manage depression, anxiety, irritability, psychosis and suicide risk using standard NICE mental-health principles plus Huntington-specific psychiatry input; avoid diagnostic overshadowing.^4,9,10

Preserve function and plan ahead

Review swallowing, communication, nutrition, weight, falls, mobility, contractures and daily activities repeatedly with speech and language therapy, dietetics, physiotherapy and occupational therapy.^5,11,12
Discuss capacity, safeguarding, driving, finances, family planning, advance decisions, feeding choices and palliative care early; support carers with assessment, respite and bereavement support.^1,13,6,10

Exam traps

A 36–39 CAG-repeat result is reduced penetrance, not the same as a fully penetrant 40-or-more expansion.
MRI caudate atrophy supports the diagnosis but is not diagnostic and can be normal early.
Predictive testing in an asymptomatic at-risk adult is a structured, voluntary genetics process, not a routine blood test; do not routinely test asymptomatic children.
The person may have reduced insight; obtain collateral history sensitively and do not let carers' distress alone define the need to suppress chorea.
Tetrabenazine and antipsychotics can worsen depression, cognition, rigidity, swallowing or falls; review benefit and harm repeatedly.
New deterioration may be infection, constipation, medication effect, delirium or another treatable problem, not inevitable progression.

Illustrations

Caudate atrophy on MRIA coronal MRI showing caudate-head atrophy and enlargement of the frontal horns of the lateral ventricles in Huntington disease; imaging supports but does not establish the diagnosis.Frank Gaillard, Wikimedia Commons · CC-BY-SA-3.0

Key sources

This page is exam revision material, not medical advice, and must not be used for patient care. Always check drug doses against the BNF and current guidance. Full disclaimer.