CLINICAL CHARACTERISTICS

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-Sträussler-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 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.

DIAGNOSIS/TESTING: The diagnosis of genetic prion disease is established in a proband with suggestive findings and a heterozygous pathogenic variant identified by molecular genetic testing.

MANAGEMENT

No treatment of the underlying cause of genetic prion disease is available. Supportive care by a multidisciplinary team of specialists including neurologists, psychiatrists, physical therapists, occupational therapists, speech and language therapists, and social workers is recommended. Because of very rapid disease progression, close periodic monitoring by the multidisciplinary team is needed, typically every 14 days to evaluate needs for symptomatic treatment.

GENETIC COUNSELING

Genetic prion disease is inherited in an autosomal dominant manner. Some individuals diagnosed with genetic prion disease may have a parent who is heterozygous for a pathogenic variant (some of whom may be asymptomatic because of reduced penetrance). Other individuals with genetic prion disease may have the disorder as the result of a pathogenic variant. Each child of an individual with a pathogenic variant has a 50% chance of inheriting the variant. Although predictive testing (i.e., testing of asymptomatic at-risk adults) is possible, the capabilities and limitations of predictive testing as well as possible socioeconomic and medical care issues should be discussed in the context of formal genetic counseling prior to testing. Predictive testing in minors (i.e., testing of asymptomatic at-risk individuals younger than age 18 years) is considered inappropriate.