Huntington Disease

Key Features

Essentials of Diagnosis

• Gradual onset and progression of chorea and dementia or behavioral change

• Family history of the disorder

• Responsible gene identified on chromosome 4

General Considerations

• Inherited in an autosomal dominant manner and occurs throughout the world, in all ethnic groups, with a prevalence rate of about 5 per 100,000

• The gene responsible for the disease has been located on the short arm of chromosome 4

  • There is an expanded and unstable CAG trinucleotide repeat at 4p16.3

  • Longer repeat lengths correspond to earlier age of onset and faster disease progression

• Offspring should be offered genetic counseling

• Genetic testing permits presymptomatic detection and definitive diagnosis of the disease

Clinical Findings

Symptoms and Signs

• Clinical onset is usually between 30 and 50 years of age

• Initial symptoms

  • May consist of either abnormal movements or intellectual changes

  • However, both ultimately occur

• Earliest mental changes

  • Often behavioral, with irritability, moodiness, antisocial behavior, or a psychiatric disturbance

  • However, a more obvious dementia subsequently develops

• Dyskinesia

  • May initially be no more than an apparent fidgetiness or restlessness

  • However, choreiform movements and some dystonic posturing eventually occur

• A parkinsonian syndrome with progressive rigidity and akinesia (rather than chorea) sometimes occur in association with dementia, especially in cases with childhood onset

Differential Diagnosis

• Chorea developing with no family history of choreoathetosis should not be attributed to Huntington disease, at least not until other causes of chorea have been excluded clinically and by appropriate laboratory studies

• In younger patients, self-limiting Sydenham chorea develops after group A streptococcal infections on rare occasions

• Other nongenetic causes of chorea

  • Stroke

  • Systemic lupus erythematosus and antiphospholipid antibody syndrome

  • Paraneoplastic syndromes

  • Infection with HIV

  • Various medications

• If progressive intellectual failure is the sole presentation, it may not be possible to distinguish Huntington disease from other causes of dementia unless there is a characteristic family history or a dyskinesia develops

• Dentatorubral-pallidolysian atrophy

  • A clinically similar autosomal dominant disorder

  • Uncommon except in persons of Japanese ancestry

  • Manifested by chorea, dementia, ataxia, and myoclonic epilepsy

  • Due to a mutant gene mapping to 12p13.31

Diagnosis

Imaging Studies

• CT scanning or MRI usually demonstrates cerebral atrophy and atrophy of the caudate nucleus in established cases

• Positron emission tomography (PET) has shown reduced striatal metabolic rate

Treatment

Medications

• Dopamine receptor blockers, such as phenothiazines or haloperidol, may control the dyskinesia and any behavioral disturbances

• Haloperidol

  • Initial dose is 1 mg orally once or twice daily

  • Dose is increased every 3 or 4 days, depending on the response

• Tetrabenazine

  • Interferes with the vesicular storage of biogenic amines

  • Used ...