April 27, 2015: Familial Fatal Insomnia
April 27, 2015
Familial Fatal Insomnia
Familial fatal insomnia (FFI) is a hereditary prion disease and form of a transmissible spongiform encephalopathy (TSE). It is caused by a genetic mutation in the prion-protein (PrP) gene (PRNP) at codon 178 on chromosome 20. The onset of FFI is usually around the 5th to 6th decade with a mean survival of approximately one and a half years from symptom onset. It is inherited as an autosomal dominate trait with a presumed high penetrance, affecting both men and women. Early on, patients will complain of diminished vigilance and an inability to initiate and maintain their sleep cycle. As the disease progresses, autonomic instability will often settle in resulting in hypertension, lacrimation, salivation, and impotence. Hallucinations, such that patients are acting out dreams, will then become more apparent, leaving a feeling of a psychotic disorder. Movement disorders, including myoclonus and pyramidal tract dysfunction will develop as patients become more hypersomnolent and difficult to arouse. On electroencephalography, loss of sleep spindles and K complexes are evident, demonstrating fragmentation of sleep patterns. In contrast to CJD, deposition of the aberrant isoform of PrP, is less in FFI. Although less, the deposition is usually more widespread and affects grey matter structures.
- Montagna P Gambetti P, Cortelli P, Lugaresi E. Familial and sporadic fatal insomnia. Lancet Neurology 2003; 2(3): 167-176.
Submitted by James Addington, M.D. Resident Physician, Department of Neurology, University of Virginia
Disclosures: Dr. Addington is a member of the Residents & Fellows Section of Neurology.