Epidemiology

Onset between 30 and 50 years of age

Average life expectancy ˜15 years

Male = female

Cardinal features

Triad of dyskinesia, dementia, and behavioral abnormalities

Autosomal dominant with complete penetrance

Chromosome 4

Unstable CAG trinucleotide repeat

Clinical features

Dyskinesia

Chorea

Dysarthria

Dystonia

Rigidity

Dementia

Subcortical type

Impaired cognitive flexibility

Psychomotor difficulties

Difficulties with complex tasks

Language and memory intact until late in disease

Behavioral abnormalities

Often herald onset of illness

Irritability/aggression common

Depression (30%-50%)—may precede onset of motor abnormalities by several years

Increased suicidality and suicide rate (up to 25% attempt suicide at least once)

Mania/hypomania

Anxiety

Obsessive compulsive disorders

Psychosis

Sexual disorders

Diagnostic considerations

DNA testing is definitive and is available for patients and potential carriers, including a fetus

Central nervous system imaging demonstrates atrophy of the caudate and putamen

Functional imaging reveals decreased metabolism in the caudate nucleus

Management considerations

Progressive illness with no cure

Symptom management is the mainstay of treatment

Dyskinesia

Dopamine antagonists (e.g., antipsychotics) may reduce the severity of the dyskinesia and behavioral abnormalities

Consider antipsychotics with decreased inherent risk for extrapyramidal symptoms and tardive dyskinesia

Dementia

No specific treatments available for management of cognitive impairment

Behavioral abnormalities

Aggression

•

Management of aggression should target underlying cause:

Antipsychotics for aggression secondary to psychosis

Antidepressants for depression-related suicidality

Mood stabilizers for mania-related agitation

Propranolol for general aggression and irritability

Depression

Selective serotonin reuptake inhibitors (SSRIs) are the mainstay of treatment

Consider mirtazapine in patients with anorexia and insomnia

Careful monitoring of suicide risk, including access to weapons

Mania/hypomania

•

Management may entail use of mood stabilizers (e.g., lithium, valproic acid, carbamazepine) and benzodiazepines

Psychosis

•

Consider antipsychotics with decreased inherent risk for extrapyramidal symptoms and tardive dyskinesia