Introduction

Spinocerebellar ataxia type 2 (SCA2) is a neurodegenerative disease caused by expansion of an unstable CAG repeat in the SCA2 or ataxin-2 gene on human chromosome 12. Ataxin-2 is a member of a novel protein family of unknown function that is evolutionarily conserved. The wide separation between normal and pathological repeat ranges seen in other CAG repeat disorders is not present in SCA2.

Phenotype

The first description of what is now genotypically con- firmed as SCA2 occurred in several families in the province of Holguin in Cuba (Orozco et al., 1989, 1990; Santos et al., 1999). The majority were of Caucasian Spanish ancestry. In addition to ataxic gait and other cerebellar findings, many patients had slow saccadic eye movements. Tendon reflexes were brisk during the first years of life, but absent several years later.

Independently, Wadia and Swami (1971) in India noticed a subset of patients with inherited ataxias who appeared to have greatly reduced saccadic eye movement velocities. However, subsequent genotyping of these families has indicated that this population was not genetically homogenous and some patients carried mutations in other ataxia genes (Wadia et al., 1998).

Analysis of a large number of SCA2 pedigrees has indicated a wide range of phenotypic manifestations that make SCA2 indistinguishable from other SCAs in the individual patient (Table 27.1). However, when compared as a group, certain phenotypic features appear that are more common in SCA2 than in other ataxias, such as slow saccades, peripheral neuropathy, and dementia.

Ataxia

Ataxia is universally present and usually a presenting sign, although some Cuban patients may present with muscle cramps. A subclinical neuropathy may be identified before any other clinical signs (Velazquez and Medina, 1998).