Huntington's Disease and Huntington's Disease-like Syndromes

An Overview

Felix Gövert and Susanne A. Schneider


Curr Opin Neurol. 2013;26(4):420-427. 

In This Article

Dentatorubral-pallidoluysian Atrophy

Dentatorubral-pallidoluysian atrophy (DRPLA) shares many key characteristics of Huntington's disease and the HDLs. It is caused by an expanded CAG trinucleotide repeat namely on the atrophin 1 (ATN1) gene on chromosome 12p13.31 and is inherited in an autosomal dominant fashion.[39–41] The repeat length correlates inversely with age of onset and directly with disease severity. Normal alleles range from 8 to 25 repeats, whereas in DRPLA patients repeat expansions range from 49 to 88. Like in Huntington's disease and other polyglutamine diseases the phenomenon of anticipation occurs with an increase in repeat length for paternal transmission.[41,42] DRPLA clusters in Japan, where it is relatively more common and the prevalence is estimated to be similar to the prevalence of Huntington's disease. The condition is rare in other regions.[8]

The average age of onset of DRPLA is between 20 and 30 years and leads to death within 10–15 years.[43] The clinical presentation of DRPLA is, however, considerably heterogeneous with an age-dependent phenotype. Juvenile-onset cases develop severe progressive myoclonus epilepsy and cognitive decline, whereas in adults ataxia, choreoathetosis and dementia represent the cardinal features.[44] The common MRI findings in DRPLA are atrophy of the cerebellum and the brainstem, in particular the pontine tegmentum. Furthermore, in adult-onset DRPLA diffuse high signal intensity lesions in the cerebral white matter are observed. The typical neuropathological findings are a combined degeneration of the dentatorubral and pallidoluysian systems. In juvenile-onset DRPLA patients cortical involvement is described, which may explain the severe cognitive deterioration and epilepsy in these patients.[45]