(Huntington Chorea; Chronic Progressive Chorea; Hereditary Chorea)
Huntington disease is an autosomal dominant disorder characterized by chorea and progressive cognitive deterioration, usually beginning during middle age. Diagnosis is by genetic testing. Treatment is supportive. Counseling about genetic testing is recommended for 1st-degree relatives.
Huntington disease affects both sexes equally. The caudate nucleus atrophies, the inhibitory medium spiny neurons in the corpus striatum degenerate, and levels of the neurotransmitters γ-aminobutyric acid (GABA) and substance P decrease.
Huntington disease results from a gene mutation causing abnormal repetition of the DNA sequence CAG, which codes for the amino acid glutamine. The resulting gene product, a large protein called huntingtin, has an expanded stretch of polyglutamine residues, which accumulate within neurons and lead to disease via unknown mechanisms. The more CAG repeats, the earlier the onset of disease and the more severe its expression (phenotype). The number of repeats can increase with successive generations and, over time, lead to increasingly severe phenotypes within a family (called anticipation).
Symptoms and Signs
Symptoms and signs develop insidiously, starting at about age 35 to 40, depending on phenotype severity. Dementia or psychiatric disturbances (eg, depression, apathy, irritability, anhedonia, antisocial behavior, full-blown bipolar or schizophreniform disorder) develop before or simultaneously with the movement disorder. Abnormal movements appear; they include chorea, tics, and myoclonic jerks. Typical features include a bizarre, puppet-like gait, facial grimacing, inability to intentionally move the eyes quickly without blinking or head thrusting (oculomotor apraxia), and inability to sustain a motor act (motor impersistence), such as tongue protrusion.
The disorder progresses, making walking impossible and swallowing difficult; it results in severe dementia. Most patients eventually require institutionalization. Death usually occurs 13 to 15 yr after symptoms begin.
Diagnosis is based on typical symptoms and signs plus a positive family history and is confirmed by genetic testing. Neuroimaging helps identify caudate atrophy and often some frontal-predominant cortical atrophy.
Because the disease is progressive, end-of-life care should be discussed early (see The Dying Patient).
Treatment is supportive. Chorea and agitation may be partially suppressed by antipsychotics (eg, chlorpromazine 25 to 300 mg po tid, haloperidol 5 to 45 mg po bid, risperidone 0.5 to 3 mg po bid, olanzapine 5 to 10 mg po once/day, or clozapine 12.5 to 100 mg po once/day or bid). In patients taking clozapine, WBC counts must be done frequently because agranulocytosis is a risk. The antipsychotic dose is increased until intolerable adverse effects (eg, lethargy, parkinsonism) develop or symptoms are controlled. Alternatively, tetrabenazine may be used. The dose is started at 12.5 mg po once/day and increased to 12.5 mg bid in the 2nd wk, 12.5 mg tid in the 3rd wk, and sequentially up to a total of 33.3 mg po tid as needed to control symptoms or until intolerable adverse effects occur. Adverse effects can include excessive sedation, akathisia, parkinsonism, and depression. Depression is treated with antidepressants.
Therapies currently under study aim to reduce glutamatergic neurotransmission via the N-methyl-d-aspartate receptor and to bolster mitochondrial energy production. Treatments that aim to increase GABAergic function in the brain have been ineffective.
People who have 1st-degree relatives with the disease, particularly women of childbearing age and men considering having children, should be offered counseling and genetic testing (see also Prenatal Genetic Counseling and Evaluation).
Last full review/revision January 2013 by Hector A. Gonzalez-Usigli, MD; Alberto Espay