Spinocerebellar Ataxia Type 7 Sans Retinal Degeneration: A Phenotypic Variability

Autosomal dominant cerebellar ataxia (ADCA) was classified into Type I, Type II, and Type III, based on the clinical phenotypes by Harding. ADCA Type I presents with both cerebellar and noncerebellar signs and includes SCA1–SCA4, SCA8, SCA10, SCA12-SCA23, SCA25, SCA27, SCA28, and SCA32–SCA36. ADCA Type II consists of syndromes in association with pigmentary retinopathies and includes SCA7. ADCA Type III includes mostly pure cerebellar syndromes and includes SCA5, SCA6, SCA11, SCA26, SCA30, and SCA31.[2] Now, ADCA has been replaced by SCA. SCA7 belongs to ADCA Type II phenotype. SCA7 is caused by the expansion of CAG trinucleotide repeats in exon 3 of ATXN7 gene on the chromosome 3p12–21.1. The gene encodes for the protein ataxin-7. Ataxin-7 is an 892-amino acid nuclear protein of unknown function. The polyglutamine expansion in the N-terminal segment of ataxin-7 exerts a toxic effect on the cerebellar Purkinje cells. In the healthy individuals, CAG repeats range from 4 to 19. The repeat length of 28–33 is regarded as mutable normal alleles. Repeats of 34 and 35 are alleles with reduced penetrance. Repeats above 37 are the pathogenic full-penetrance alleles.[3] The prevalence of SCA7 has been reported to be the highest in South Africa and Scandinavian region. The age of onset can be early (<25 years) or late (>40 years) onset. The phenotypic abnormalities are dependent on the repeat lengths. Cerebellar ataxia is seen in all age onsets. Retinal degeneration precedes cerebellar ataxia with higher repeat length and in early onset and vice versa with lower repeat sizes and in late onset. This is due to early-onset toxicity in the retinal tissue than in cerebellum from higher length of a pathogenic polyglutamine stretch in ataxin-7 protein.