Journal Article

Gerstmann-Sträussler-Scheinker syndrome with de novo PRNP P102L mutation in a young adult

Aisling, Ryan, Alan, Power, Tze How, Mok, Helena, Moore

2023

Overview

IntroductionGerstmann-Sträussler-Scheinker (GSS) syndrome, caused by the PRNP P102L mutation is cha- racterized by slowly ascending distal lower limb sensory loss, cerebellar ataxia, pyramidal signs, followed later by cognitive decline, with a median survival of 4-5 years. Prevalence is around 1-10/100,000,000, with an estimated 56 families described worldwide. P102L-GSS is associated with PrP amyloid deposition and subsequent spongiform change in the cortex, basal ganglia, cerebellum and brainstem. Other distinct clinical manifestations of P102L include pure cognitive and CJD-like syndromes.CaseWe describe a 28-year-old female with a 4-year history of slowly progressive ataxia, dysarthria and spastic paraparesis; she now requires the aid of one crutch to mobilise. MRI of brain and spinal cord were unremarkable. Whole exome sequencing returned a P102L mutation in PRNP; codon 129 was valine homozygous. Both parents tested negative, suggesting a de novo mutation. She was referred for specialist evaluation at the NHS National Prion Clinic in London, and was enrolled in the UK National Prion Monitoring Cohort.DiscussionP102L co-allelic with 129V is extremely rare in GSS. We speculate that this may be related to the younger than average age of onset in this case and the clinical phenotype with prominent spasticity.

• Publisher: BMJ Publishing Group Ltd,BMJ Publishing Group LTD
• Subject: Association of British Neurologists: Annual Meeting Abstracts 2023 / Ataxia / Mutation / Young adults