Chapter 32 - Spinocerebellar Ataxia 17 and Huntington's Disease-like 4

Abstract

Spinocerebellar ataxia 17 (SCA17) or Huntington's disease-like 4 (HDL4) is a rare neurodegenerative disorder (MIM#607136) caused by polyglutamine expansions, above 43–44 repeats. This feature has consequences for genetic counseling, particularly the existence of reduced penetrance forpresymptomatic testing. It belongs to a group commonly referred to as polyglutaminopathies, which also includes Huntington's disease (HD), spinal and bulbar muscular atrophy, dentatorubral pallidoluysian atrophy (DRPLA), and 6 forms of autosomal dominant cerebellar ataxias (ADCA). This is one of the rarer forms of autosomal dominant cerebellar ataxias, but the associated phenotype is often severe, involving various systems (cerebral cortex, striatum, and cerebellum) with an extremely variable age at onset (range: 3–75 years) and clinical presentation. A Huntington's disease-like phenotype has also been reported with SCA17 expansions, and this gene is accounted for a small proportion of patients with a Huntington's disease-like phenotype and cerebellar signs.