Snapshot A 30-year-old woman presents with a two year history of anxiety, gait instability, and progressively worsening tics. She has no family history of neurologic disease, but her father committed suicide at age 32. MRI scan of the brain shows atrophy of the cerebral cortex and caudate nucleus. Introduction Definition autosomal dominant, incurable neurodegenerative disorder characterized by choreiform movements, cognitive decline, mood dysfunction Epidemiology Usually begins between ages 30-50, but may begin as early as infancy (juvenile HD if age of onset < 20), or in older age Both sexes are affected equally Pathophysiology Autosomal dominant CAG triplet repeat expansion in one allele of the HD (huntingtin) gene on chromosome 4 Number of CAG repeats determines presence of disease < 29 repeats: no disease, or normal phenotype 30-35 repeats: intermediate (no risk to the individual, but increased risk for offspring) allele 36-39 repeats: incomplete penetrance allele > 39 repeats: full penetrance allele Number of CAG repeats may increase with subsequent generations,(anticipation) particularly with paternal transmission HD mutation results in neuronal death, particularly in the caudate nucleus and putamen (basal ganglia) Age of onset and severity of disease is inversely correlated with number of CAG repeats Presentation Symptoms involuntary movements chorea, or choreiform movements (dancelike hyperkinetic movements) athetotic (or choreathetotic) movements tics or grimacing ataxia falls cognitive deterioration memory loss language disability psychiatric dysfunction depression suicidal ideation and suicide irritability and anxiety psychosis sleep disturbance aggresivity or impulsivity substance abuse hyper or hyposexuality other symptoms weight loss swallowing difficulty and aspiration Evaluation Labs molecular genetic testing for number of CAG repeats in each of the HD alleles is diagnostic Imaging MRI shows atrophy of caudate and putamen, as well as general cerebral atrophy Differential Tourette's (Tic) disorder Syndenham chorea Schizophrenia Tardive dyskinesia Wilson's disease Spinocerebellar ataxia Treatment No curative treatment or treatment altering disease progression Supportive treatment can be highly effective reserpine, tetrabenazine, or atypical antipsychotics for involuntary movements SSRIs for depression atypical antipsychotics for psychosis and behavior problems benzodiazepines for sleep disturbance Genetic counseling should be offered for patients, family members, and at-risk offspring Prognosis, Prevention, and Complications Condition is inevitably fatal Average prognosis is approximately 20 years from symptom onset