Fatal familial insomnia

Fatal insomnia is a rare disorder that results in trouble sleeping. The problems sleeping typically start out gradually and worsen over time. Other symptoms may include speech problems, coordination problems, and dementia. It results in death within a few months to a few years. It is a prion disease of the brain. It is usually caused by a mutation to the protein PrPC. It has two forms: fatal familial insomnia (FFI), which is autosomal dominant and sporadic fatal insomnia (sFI) which is due to a noninherited mutation. Diagnosis is based on a sleep study, PET scan, and genetic testing. Fatal insomnia has no known cure and involves progressively worsening insomnia, which leads to hallucinations, delirium, confusional states like that of dementia, and eventually death. The average survival time from onset of symptoms is 18 months. The first recorded case was an Italian man, who died in Venice in 1765. The disease has four stages: Other symptoms include profuse sweating, pinpoint pupils, the sudden entrance into menopause for women and impotence for men, neck stiffness, and elevation of blood pressure and heart rate. Constipation is common as well. As the disease progresses, the person becomes stuck in a state of pre-sleep limbo, or hypnagogia, which is the state just before sleep in healthy individuals. During these stages, people commonly and repeatedly move their limbs as if dreaming. The age of onset is variable, ranging from 18 to 60 years, with an average of 50. The disease can be detected prior to onset by genetic testing. Death usually occurs between 7–36 months from onset. The presentation of the disease varies considerably from person to person, even among people within the same family. The gene PRNP that provides instructions for making the prion protein PrPC is located on the short (p) arm of chromosome 20 at position p13. Both people with FFI and those with familial Creutzfeldt–Jakob disease (fCJD) carry a mutation at codon 178 of the prion protein gene. FFI is also invariably linked to the presence of the methionine codon at position 129 of the mutant allele, whereas fCJD is linked to the presence of the valine codon at that position. 'The disease is where there is a change of amino acid at position 178 when an asparagine (N) is found instead of the normal aspartic acid (D). This has to be accompanied with a methionine at position 129.' Diagnosis is suspected based on symptoms. Further work up often include a sleep study and PET scan. Confirmation of the familial form is by genetic testing.