Huntington disease: finding the gene and after.

Huntington disease is an autosomal dominant disorder that usually begins in mid-life and is characterized by progressive choreiform movements and dementia. Approximately 5% of patients develop symptoms prior to 14 years of age. In most juvenile cases, the gene is transmitted from the father. In children the clinical course is marked by mental deterioration or behavioral abnormalities, gait disturbances usually the consequence of rigidity, cerebellar signs, and seizures. The pathologic findings are highlighted by atrophy of the caudate. Atrophy also is observed on brain imaging, while positron emission tomography demonstrates marked caudate hypometabolism which antedates the appearance of the clinical disease. Cell death in the striatum primarily affects medium and small GABA-containing neurons, representing the striatal output projections. Somatostatin-containing neurons and cholinergic neurons are spared. The gene for Huntington disease has been localized in close proximity to the tip of the short arm of chromosome 4. The gene product and the manner by which it induces selective cell death is still unknown but should become evident in the near future.