Huntington Disease

Excerpt

Clinical characteristics: Huntington disease (HD) is a progressive disorder of motor, cognitive, and psychiatric disturbances. The mean age of onset is 35 to 44 years, and the median survival time is 15 to 18 years after onset.

Diagnosis/testing: The diagnosis of HD rests on positive family history, characteristic clinical findings, and the detection of an expansion of 36 or more CAG trinucleotide repeats in HTT.

Management: Treatment of manifestations: Pharmacologic therapy including typical neuroleptics (haloperidol), atypical neuroleptics (olanzapine), benzodiazepines, or the monoamine-depleting agent tetrabenazine for choreic movements; anti-parkinsonian agents for hypokinesia and rigidity; psychotropic drugs or some types of anti-seizure medication for psychiatric disturbances (depression, psychotic symptoms, outbursts of aggression); valproic acid for myoclonic hyperkinesia. Supportive care with attention to nursing needs, dietary intake, special equipment, and eligibility for state and federal benefits.

Prevention of secondary complications: Attention to the usual potential complications in persons requiring long-term supportive care and to side effects associated with pharmacologic treatments.

Surveillance: Regular evaluations of the appearance and severity of chorea, rigidity, gait abnormalities, depression, behavioral changes, and cognitive decline; routine assessment of functional abilities using the Behavior Observation Scale Huntington (BOSH) and the Unified Huntington's Disease Rating Scale (UHDRS).

Agents/circumstances to avoid: L-dopa-containing compounds (may increase chorea), alcohol consumption, smoking.

Other: Children and adolescents with a parent with HD may benefit from referral to a local HD support group for educational materials and psychological support.

Genetic counseling: HD is inherited in an autosomal dominant manner. Offspring of an individual with a pathogenic variant have a 50% chance of inheriting the disease-causing allele. Predictive testing in asymptomatic adults at risk is available but requires careful thought (including pre- and post-test genetic counseling) as there is currently no cure for the disorder. However, asymptomatic individuals at risk may be eligible to participate in clinical trials. Predictive testing is not considered appropriate for asymptomatic at-risk individuals younger than age 18 years. Prenatal testing by molecular genetic testing and preimplantation genetic testing are possible.