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Dentatorubral-pallidolysial Atrophy, DRPLA - ATN1

Haw-River-Syndrom, HRS

Clinical Features

The dentatorubral-pallidolysial atrophy (DRPLA) is clinically characterized by cerebellar ataxia, myoclonic epilepsy, and, as disease progresses, choreoathetosis and dementia. In some patients a differentiation of the choreatic movement disorder from Huntington disease is particularly difficult. Neuropathological changes mainly include neuronal degeneration and are found predominantly in the dentatorubral and the pallidolysial system of the CNS.

The Haw-River syndrome is clinically characterized by cerebellar ataxia, choreoathetosis and dementia. Myoclonic epilepsy is not observed. Wide-spread subcortical demyelinations and calcifications of the basal ganglia are characteristic neuropathological features.

Genetic Information

The DRPLA and the Haw-River syndrome are caused by expansion of CAG trinucleotide repeats in the short arm of chromosome 12 (12p13.31). The CAG triplets code for a sequence of glutamine stretches in the ATN1 gene product. The increased number of glutamine residues presumably leads to structural changes of the protein. The function of the corresponding protein has not yet been elucidated.

In the normal population 8-26 CAG triplets are found. Pathologically altered DRPLA genes carry 54-68 triplets. The DRPLA and the Haw-River syndrome follow autosomal inheritance. Inheritance by the male germline tends to further increase triplet repeat length. Repeat length appears to be stable in the passage through the female germline.

Prevalence

Rare in Europe

more common in the asian population (approx. 1 : 50 000)

Diagnostic