Clinical Guidance

Genetic prion disease generally manifests with cognitive difficulties, ataxia, and myoclonus (abrupt jerking movements of muscle groups and/or entire limbs). The order of appearance and/or predominance of these features and other associated neurologic and psychiatric findings vary. The three major phenotypes of genetic prion disease are genetic Creutzfeldt-Jakob disease (gCJD), fatal familial insomnia (FFI), and Gerstmann-Strussler-Scheinker (GSS) syndrome. Although these phenotypes display overlapping clinical and pathologic features, recognition of these phenotypes can be useful when providing affected individuals and their families with information about the expected clinical course. The age at onset typically ranges from ages 50 to 60 years. The disease course ranges from a few months in gCJD and FFI to a few (up to 4, and in rare cases up to 10) years in GSS syndrome. provides information on the frequency of neurologic features in the most frequent genetic prion disease phenotypes that emerge during the disease course. While some PRNP pathogenic variants are associated with specific neuropathologic phenotypes, individuals in the same family who are heterozygous for the same PRNP variant may develop distinct clinicopathologic phenotypes . Table 2. Select Features of Genetic Prion Disease by Phenotype and PRNP Pathogenic Variant Feature | % of Persons w/Feature by Phenotype PRNP Variant

Diagnostic Criteria

Suggestive Findings

Genetic prion disease should be suspected in individuals with the following clinical, laboratory, and imaging findings and family history.

Clinical

Genetic prion disease is a progressive neurodegenerative syndrome with rapid evolution of clinical signs (which reflect involvement of various neuroanatomic structures) – typically, dementia in combination with the following developing within a few months or (rarely) a few years:

Management Guidelines

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual diagnosed with genetic prion disease, the evaluations summarized in this section (if not performed as part of the evaluation that led to the diagnosis) are recommended. Because of very rapid disease progression and short survival time after the diagnosis, evaluations for supportive care must be performed early. They include the following:

Surveillance Guidelines

Because of very rapid disease progression, close periodic monitoring by the multidisciplinary team is needed, typically every 14 days to evaluate need for treatment of symptoms.

Source: GeneReviews — "Genetic Prion Disease"