HUNTINGTON DISEASE

HUNTINGTON  DISEASE

A 34-year-old man comes to the clinic for an evaluation of strange spontaneous movements that have been occurring lately. Recently, while sitting at a family dinner, the patient experienced uncontrolled grimacing with grunting. His father died at the age of 41 from “dementia.”

Definition. A genetic degenerative brain disorder.

Etiology. Huntington disease is caused by the presence of the HD gene located on chromo- some 4p. The gene contains a CAG trinucleotide repeat expansion that codes for a protein called huntingtin. The HD mutation leads to abnormal cleavage of the huntingtin protein, interfering with nuclear mechanisms, and causing cell death. The disease is inherited in an autosomal dominant fashion. Successive generations tend to have the disease occuring at an earlier age. This is called anticipation.

Clinical Presentation. The clinical hallmarks of the disease include chorea and behavioral disturbance. Onset is usually in the fourth or fifth decade and can begin with either chorea or behavioral change. The personality changes consist of irritability, anger, paranoia, or signs of depression. Antisocial behavior may develop. The chorea may begin as fidgeting that progresses to sudden movements of the trunk or limbs. Gait is poorly coordinated and has a choreic quality. Memory is usually preserved until late in the disease but lack of judgment, disinhibi- tion, and inattention are early manifestations. There is frequently an associated depression. Dementia becomes severe later in the disease.

Diagnosis. Diagnosis is made by genetically testing for the presence of the CAG trinucleotide DNA repeat expansion. There is a 50% chance of passing it on to children. CT scanning shows cerebral atrophy. Atrophy of the caudate nucleus is severe later.

Treatment. Tetrabenazine helps the movement disorder of Huntington disease but will not reverse or cure the underlying disease process. Death occurs 15–20 years after the diagnosis. Haloperidol or clozapine can be used to control behavioral changes.