Genetic prion disease caused by a Q160X PRNP mutation presenting with an orbitofrontal syndrome (P4.100)

OBJECTIVE: To describe the phenotype of a patient with a PRNP Q160X mutation. BACKGROUND: The nonsense mutation in PRNP Q160X leads to a truncated form of the prion protein linked to genetic Creutzfeldt-Jakob disease (CJD) featuring slowly progressive early-onset dementia and gastrointenstinal symptoms. Episodic memory loss in the absence of ataxia or myoclonus have been associated with CJDQ160X. DESIGN/METHODS: We report a case of genetic CJDQ160X presenting with orbitofrontal, and later, GI, symptoms. Whole exome sequencing was done on the proband and both parents. RESULTS: A previously healthy 31 year-old gentleman presented with 4-years of aggressive outbursts, drug abuse, hypersexuality and impaired judgment. He subsequently developed visual and speech difficulties, forgetfulness and impairment of instrumental activities of daily living. His behavioral symptoms improved as other dimensions of cognition started to be affected. He was initially believed to have schizophrenia and Alzheimer’s disease. His review of systems revealed weight loss, erratic blood pressure and painful paresthesias of hands and feet. His paternal grandfather, two of his siblings and a paternal aunt had history of dementia. His exam revealed mixed aphasia, delayed word recall, apraxia, dysarthria, paratonia in 4 extremities and slow wide-base gait. His mini-mental state examination score was 5 out of 30. Brain magnetic resonance imaging showed severe atrophy of the bilateral anterior temporal lobes, left greater than right parietal lobe and bilateral angular gyri. Deep nuclei, cerebellar and subcortical white matter showed no major changes and there was no restricted diffusion. Genetic testing confirmed a mutation in codon Q160X of PRNP. CONCLUSIONS: Genetic CJDQ160X may produce slowly progressive dementia with a behavioral phenotype and GI symptoms. Genetic forms of CJD may not show typical restricted diffusion changes in neuroimaging. Family history of dementia and the presence of peripheral neuropathy should raise suspicion for genetic CJD in early onset dementia. Disclosure: Dr. Rojas has nothing to disclose. Dr. Fong has nothing to disclose. Dr. Coppola has nothing to disclose. Dr. Legati has nothing to disclose. Dr. Karydas has nothing to disclose. Dr. Rankin has nothing to disclose. Dr. Bang has nothing to disclose. Dr. Miller has nothing to disclose. Dr. Geschwind has received personal compensation for activities with Best Doctors, Guidepoint Global, and Quest Diagnostics. Dr. Geschwind has received research support from the National Institutes of Health/National Institute of Aging, the Tau Consortium