Background Mutations in the prion gene (PRNP) are rare causes of autosomal dominant movement disorders. One-nine extra octapeptide repeat insertions (OPRIs) in this gene lead to heterogeneous phenotypes. Only four families with 8 OPRIs have been reported, one of these reports described a Swedish three generation's kindred in which several of the affected members -4 of 7- displayed chorea. Following the exclusion of Huntington's disease (HD), the disorder was labelled Huntington disease-like 1 (HDL1), and was subsequently found to be due to a PRNP mutation.^{1 2} All cases in the Swedish kindred were homozygous for methionine (MM) at codon 129 and displayed variable age of onset. The mean disease duration for this kindred was 15 years (range 11–23 years), the longest described for 8 OPRIs. Here we describe clinical features of one of the family members with HDL1, who had a disease duration of 19 years and provide an update on this kindred.

Case history The subject was born in 1959 and described previously as III:3.¹ His mother was also affected by HDL1. The subject was adopted at the age of 3 and was in normal health until the age of 29. He then developed insidious personality changes, severe apathy, cognitive decline and bizarre behaviour. Three years later he developed dyspraxia, urinary incontinence, short-term memory impairment, and his speech was limited to short answers. Gait difficulties were evident, although chorea was not documented in the course of disease. A CT scan of the brain revealed general atrophy with particularly reduced volume in the temporal lobes. At the age of 34 he displayed worsened aggressive behaviour, severe dementia with expressive aphasia, dysphagia and seizures. His treatment included tetrabenazine, carbamazepine and zuclopentixol. A stooped posture with antecollis, bradykinesia and rigidity were evident, and may have been due to medication (see video segments). It is possible that this medication may have prevented the appearance of chorea. A HMPAO-SPECT scan showed marked reduction of blood flow in both parietotemporal areas. EEG showed generalised slowness with a 2–4 Hz frequency. Gradually the subject became wheelchair-bound and progressed into a state of akinetic mutism with generalised spasticity. In the last stages of disease he had frequent seizures until dying of pneumonia at the age of 48.

Conclusion HDL1 and other familial prion diseases caused by extra OPRIs should be considered as differential diagnosis in individuals with family histories and phenotypes suggestive of HD, but who lack the mutation for this disease.

References 1. Xiang F, et al. Am J Hum Genet 1998;63:1431–8.

2. Moore R, et al. Am J Hum Genet 2001;69:1385–8.