A novel 8-octapeptide repeat insertion in PRNP causing Huntington disease-like 1 in a Chinese family: a case report and literature review.

Background: Approximately 1-3% of patients with Huntington disease (HD) present with HD-like phenotype but test negative for the HD gene, suggesting other causes.

Methods: This study presents the first case of Huntington disease-like 1 (HDL-1) in a Chinese family and summarises the clinical features of previously reported HDL-1 cases and patients with octapeptide repeat insertion (OPRI) mutations.

Results: The proband, a 36-year-old woman, presented with progressive involuntary movements, bradykinesia, cognitive decline and personality changes over 6 years, worsening over the past year. Similar manifestations were noted in her grandmother, father and aunt. Genetic testing revealed an 8-OPRI mutation in PRNP, confirming HDL-1. Neuroimaging showed increased T2-Fluid Attenuated Inversion Recovery (FLAIR) signals in the hippocampi and atrophic changes in the frontal and parietal lobes. Electroencephalography indicated a slowed background rhythm. A 1-year follow-up visit showed amelioration of choreic movements. A literature review identified five families with HDL-1, with age of onset ranging from 18 years to 54 years and disease duration from 3 months to over 20 years. Common manifestations included movement disorders, dementia, personality changes and heterogeneous symptoms such as epilepsy. Imaging showed ventricular enlargement and diffuse brain atrophy, primarily affecting the basal ganglia, frontal lobes, temporal lobes and cerebellum. Pathologically, prion protein antibody staining was positive, although spongiform changes were not prominent.

Conclusion: These cases highlight the importance of considering familial prion diseases in patients with hereditary chorea and a negative HD gene test. Careful attention to treatment and follow-up can provide valuable insights for managing these patients.