Introduction

A ten-generation family with a clinically mild autosomal dominant form of spinocerebellar ataxia (SCA) was identified in 1992 (Ranum et al., 1994). This Caucasian kindred has two major branches that both trace their ancestries to the paternal grandparents of President Lincoln (Fig. 30.1). Abbreviated versions of the two branches of the family are shown in Fig. 30.2. DNA has been obtained from 215 members (60 affected) of this kindred. After excluding linkage to the known ataxia loci, a genome wide screen mapped the disease locus, spinocerebellar ataxia type 5 (SCA5), to chromosome 11q13 (Ranum et al., 1994). Although disease onset is typically in the third or fourth decade, it can range from 10 to 68 years. Signs and symptoms progress over several decades, beginning with a mild disturbance of gait, incoordination of upper extremities, and slurred speech.

SCA5 primarily affects the cerebellum and is clinically more benign (Ranum et al., 1994) than other SCAs (Gouw et al., 1994; Yagishita and Iouue, 1997). In general, the adult-onset cases appear similar to patients with SCA6 (Zhuchenko et al., 1997) and to previously described families with relatively ‘pure’ forms of cerebellar ataxia (Holmes, 1907; Harding, 1983). Whereas adult-onset SCA5 is disabling, the most striking clinical distinctions from SCA1, SCA2, SCA3, SCA4, and SCA7 are that SCA5 progresses more slowly and generally does not shorten life (Ranum et al., 1994). This clinical difference is probably due to the lack of bulbar paralysis in all of the adult-onset SCA5 patients examined. Bulbar paralysis in other forms of dominant ataxia often leads to a weakened ability to combat recurrent pneumonia (Zoghbi, 1991).