Huntington’s Disease (HD)

HD is a progressive, fatal, highly penetrant autosomal dominant disorder characterized by motor, behavioral, and cognitive dysfunction. Onset is typically between the ages of 25 and 45 years (range, 3–70 years) with a prevalence of 2–8 cases per 100,000 and an average age at death of 60 years.
HD is characterized by rapid, nonpatterned, semipurposeful, involuntary choreiform movements. Dysarthria, gait disturbance, and oculomotor abnormalities are common features. With advancing disease, there may be a reduction in chorea and emergence of dystonia, rigidity, bradykinesia, myoclonus, and spasticity. In younger patients (about 10% of cases), HD can present as an akinetic-rigid or parkinsonian syndrome (Westphal variant). HD patients eventually develop behavioral and cognitive disturbances, and the majority progress to dementia. Depression with suicidal tendencies, aggressive behavior, and psychosis can be prominent features. The disease predominantly strikes the striatum. Progressive atrophy of the caudate nuclei, which form the lateral margins of the lateral ventricles, can be visualized by MRI.

Genetic testing can be used to confirm the diagnosis and to detect at-risk individuals in the family, but this must be performed with caution and in conjunction with trained counselors, as positive results can worsen depression and generate suicidal reactions.

Etiology

HD is caused by an increase in the number of polyglutamine (CAG) repeats (>40) in the coding sequence of the huntingtin gene located on the short arm of chromosome 4. Treatment: Huntington’s Disease

Treatment involves a multidisciplinary approach, with medical, neuropsychiatric, social, and genetic counseling for patients and their families. Dopamine-blocking agents may control the chorea. Tetrabenazine,but it may cause secondary parkinsonism. Depression and anxiety can be greater problems, and patients should be treated with appropriate antidepressant and antianxiety drugs and monitored for mania and suicidal ideations. Psychosis can be treated with atypical neuroleptics such as clozapine (50–600 mg/d), quetiapine (50–600 mg/d), and risperidone (2–8 mg/d). There is no adequate treatment for the cognitive or motor decline Promitochondrial agents such as ubiquinone and creatine are being tested as possible disease-modifying therapies. Antiglutamate agents, caspase inhibitors, inhibitors of protein aggregation, neurotrophic factors, and transplantation of fetal striatal cells are areas of active research, but none has as yet been demonstrated to have a disease-modifying effect.

Huntington’s Disease–Like 1 (Hdl1), Huntington’s Disease–Like 2 (Hdl2)
HDL1 is a rare inherited disorder due to mutations of the protein located at 20p12. Patients exhibit onset of personality change in the third or fourth decade, followed by chorea, rigidity, myoclonus, ataxia, and epilepsy.
HDL2 is an autosomal dominantly inherited disorder manifesting in the third or fourth decade with a variety of movement disorders, including chorea, dystonia, or parkinsonism and dementia.