PO102 Atypical clinical phenotypes of huntington’s disease

Abstract

Huntington’s disease (HD) is an autosomal dominant neurodegenerative disease caused by CAG trinucleotide expansion in the HTT gene. Certain neurons, such as the striatal spiny neurons of the basal ganglia, are more susceptible to the damage caused by accumulation of mutant huntingtin protein. This differential vulnerability of specific neuronal populations generates a characteristic triad of progressive dementia, neuropsychiatric disease and motor abnormalities. We present three atypical clinical cases of HD with diagnostic genetic test results. Two of the patients presented with progressive spastic quadraparesis, dysarthria and cognitive decline without involuntary movements. The third patient had a relapsing psychosis for more than 10 years before presenting with motor signs. Huntington’s disease is a relatively common cause of cognitive and physical decline in younger patients. It should be considered even if they do not present with a classical phenotype. 10% of adult patients with HD do not develop chorea. They may have other involuntary movements or none at all. Additionally, drug therapy for psychiatric symptoms and the rigidity and bradykinesia of advanced disease could mask involuntary movements. Psychiatric illness can occur decades before the onset of motor symptoms. This association tends to cluster in certain families and may represent genetic heterogeneity or gene linkage.