Chapter 8 - Dentatorubral pallidoluysian atrophy

Abstract

This chapter provides an insight of the epidemiology, clinical features, imaging, genetics, pathology, diagnosis, and treatment of dentatorubral pallidoluysian atrophy (DRPLA). Most reported DRPLA cases are from Japan. DRPLA is a trinucleotide CAG repeat disorder caused by expansion of the CTG-B37 gene on chromosome 12p. The gene product, atrophin-1, is found throughout the body and the brain. Clinical heterogeneity is the rule in DRPLA. The six dominant clinical features of DRPLA are: ataxia, chorea, dementia/mental retardation, epilepsy, myoclonus, and psychiatric/behavioral symptoms. Pathologically, there is atrophy of the dentatorubral and pallidoluysian systems. As with other CAG repeat disorders, NIIs and diffuse polyglutamine expression are noted throughout the brain. DRPLA has the largest expansion and the most prominent anticipation among CAG repeat disorders, with earlier and more severe disease with paternal inheritance. DRPLA may be divided according to onset age: juvenile-onset types (< 20 years) have a progressive myoclonic epilepsy (PME) phenotype, while the adult-onset type (≥ 20 years) is primarily characterized by ataxia, chorea, and dementia. Treatment is symptomatic. The Haw River syndrome (HRS) is also discussed in the chapter.