Juvenile onset Huntington's disease--clinical and research perspectives.

Huntington's disease (HD) is an inherited neurodegenerative disorder. The mutation which causes the disease is an expansion in the number of repetitions of three nucleotides, C, A, and G in exon 1 of the huntingtin gene. The gene normally has 15 to 30 repeats and an expansion to 40 or more is associated with HD. HD usually has a mid-life onset, but a juvenile form, defined by onset of symptoms before the age of 21 years, is present in about 7% of HD cases. Juvenile HD is characterized by (1) transmission from an HD affected father, (2) an unusually large repeat size, usually of 60 or more units, and (3) unique clinical features, including rigidity and seizure disorder. Although juvenile onset is associated with a more severe neuropathological involvement, the neuropathological characteristics of juvenile HD are similar to those seen in the adult form in that the striatum bears the brunt of the illness. Clumps of protein, termed inclusion bodies, which stain positive for huntingtin and ubiquitin, are found primarily in the nucleus but also in the cytoplasm and axons in HD neurons. Research suggests that these inclusion bodies sequester a deleterious protein fragment and prolong cell life during the degenerative process of the disease. Copyright 2001 Wiley-Liss, Inc.