Chapter 27 Spinocerebellar Ataxia Type 7 Clinical Features to Cellular Pathogenesis

SCA7 is an autosomal dominant inherited neurodegenerative syndrome of progressive cerebellar ataxia and retinal degeneration that affects people on every continent. The clinical severity in SCA7 is rather broad, with cases ranging from infantile onset with early death due to nonneurological involvement to elderly presentations of isolated ataxia that progress extremely slowly. The breadth of clinical presentation and natural history stems from the marked CAG repeat instability at the SCA7 locus, making this repeat disorder the most unstable mutation of the CAG/polyglutamine repeat disease category. The pronounced anticipation, such as worsening disease severity as manifested by earlier age of disease onset and more rapid disease progression with familial transmission of a disease mutation in afflicted pedigrees made SCA7 a highly likely candidate for a causal triplet repeat mutation. Clinical evaluation of patients with SCA7 is often augmented by neuroimaging studies, which reveal marked atrophy of the cerebellum and pons, whereas a subset of patients may also demonstrate high T2 signal intensity in the transverse pontine fibers. Histological examinations of tissue from SCA7 patients have revealed extensive loss of cerebellar Purkinje cells, as well as prominent neuronal loss and gliosis in the inferior olive.