CLINICOPATHOLOGY OF SPINOCEREBELLAR DEGENERATION - ITS CORRELATION TOTHE UNSTABLE CAG REPEAT OF THE AFFECTED GENE

The recent advances in gene analysis have greatly facilitated the clas sification of autosomal dominant spinocerebellar ataxia (SCA). Analyse s of linkage in large families with SCA have assigned gene foci to at least 8 chromosomes. One gene is located in the short arm of chromosom e 6 (6p22-p23) and causes spinocerebellar ataxia type 1 (SCA1). A gene in the long arm of chromosome 14 (14q24.3-q32) underlies Machado-Jose ph disease (MJD). A third gene locus is assigned to the short arm of c hromosome 12 (12p2-pter) causing dentatorubropallidoluysian atrophy (D RPLA). The gene for spinocerebellar ataxia type 2 (SCA2) is located in the 12q23-24. Subsequently, a sporadic counterpart of hereditary oliv opontocerebellar atrophy of the Menzel type is clearly defined, and al l the syndromes (non-hereditary olivopontocerebellar atrophy, striaton igral degeneration and Shy-Drager syndrome) are now lumped under the t erm of multiple system atrophy (MSA). Oligodendroglial cytoplasmic inc lusions appear to be specific for and diagnostic of MSA. As the clinic al features in SCA are variable and often appear to overlap with one a nother, which makes accurate classification difficult if not possible, the genotype is required for their unequivocal classification. Howeve r, major neuropathological features clearly distinguish SCA1 from SCA3 /MJD cases; the medial segment of the globus pallidus and intermediola teral column lesions in SCA3/MJD, and inferior olive and cerebellar co rtical degeneration in SCA1. It has been stated that neurodegeneration in SCA3/MJD is more homogeneous than in SCA1 or SCA2 and that degener ation of the pallidoluysian system is not present in the latter. The p ertinent pathology in each of the three types of SCA is illustrated. T he background of clinicopathology and genetic analysis of dentatorubro pallidoluysian atrophy is also reviewed.