Similarities and differences in the phenotype, genotype and pathogenesis of different spinocerebellar ataxias

Abstract

Historically, the differential diagnosis of the autosomal ataxias (ADCAs) has been difficult. In 1983 Harding proposed a useful clinical classification. Since 1983 ADCAs have been increasingly characterized in terms of their genetic locus and are referred to as spinocerebeller ataxia (SCA). The overlap between the SCA phenotypes and the high variability within SCA subgroups means that, for individual patients, the underlying mutation cannot be predicted reliable purely on the basis of clinical symptoms and so diagnosis should be made on the genotype. However, for executing DNA analyses in order of clinical likelihood, neurologists may try to deduce the underlying mutation by using a clinical algorithm. In this article we not only describe such an algorithm but also plot the pathway from clinical presentation, genetic classification and mutation, abnormal protein to common neuropathology in these disorders.

Central auditory processing in patients with spinocerebellar ataxia

“…Different clinical and neuropathological studies have shown that each SCA specific genetic entity has a constellation of signs and symptoms that are related to disease duration, and with the size of trinucleotide repeat expansion (CAG). Thus, the combination of molecular genetic data and clinical signs provide useful information that serve as the basis for the classification of SCAs (Schelhaas et al, 2000;Stevanin et al, 2000).…”

Spinocerebellar ataxias

“…In 2000 Schelhaas et al published an interesting study of the pathogenesis of different SCAs as well as the phenotypic and genotypic similarities and differences between the diseases 60 . They emphasized the overlap between the phenotypes of the different forms of SCA as well as the great variation that can be observed in each SCA subtype and stated that a diagnosis should be based on genotype analysis.…”

“…They emphasized the overlap between the phenotypes of the different forms of SCA as well as the great variation that can be observed in each SCA subtype and stated that a diagnosis should be based on genotype analysis. However, they proposed a clinical algorithm to investigate the various SCAs that takes into account different key signs and symptoms, such as retinal degeneration, eye movement disturbances and the presence of pyramidal signs 60 .…”

Defining Disease Phenotypes

“…General references: O'Donnell and Zoghbi, 1995;Warren and Ashley, Jr., 1995;Monckton and Caskey, 1995;Sutherland and Richards, 1995;Warren, 1996;Schalling, 1996, 1999;Li and el Mallakh, 1997;Koshy and Zoghbi, 1997;Nance, 1997;La Spada, 1997;Mitas, 1997;Tsuji, 1997;Koeppen, 1998;Basu et al, 2000;Schelhaas et al, 2000;Stevanin et al, 2000;Lin et al, 2000;Nussbaum and Auburger, 2000;Morrison, 2000;Cummings and Zoghbi, 2000;Ohara, 2001.…”