![]() ![]() These lesions are characterized by a significant loss in the number of large neurons and astrogliosis. Autopsy examination of brain specimens reveals microscopic abnormalities in the anterior and dorsomedial thalamic nuclei bilaterally. ![]() Īs FFI progresses specific neurodegenerative changes occur. This proliferation allows for the accumulation of insoluble PrP, which is resistant to degradation by proteases. PathophysiologyĪ conformational change in the normal PrP protein results in a deviant isoform that acts as a template for self-propagation. Therefore, heterozygosity for the methionine residue (Met-Val) at codon 129 may provide a protective effect against developing FFI. The homozygous presence of methionine (Met-Met), most common in East Asians, may shorten the duration of disease or hasten the onset of disease. The substituted amino acid at position 178 interacts with a nonmutated methionine residue at the polymorphic position 129 to form the abnormal PrP isoform responsible for this distinct disease. This uniformly fatal illness is passed from parent to offspring in an autosomal dominant fashion with high phenotypic penetrance. In FFI, a missense mutation at codon 178 of the PRNP gene located on chromosome 20 results in the substitution of asparagine for aspartic acid (D178N). Loss of wild type function due to misfolding and aggregation of insoluble PrP triggers inevitable neurodegeneration and plays a central role in prion disease. While details of the physiological role of PrP remains unclear, this protein is highly expressed in the nervous system. An increased number of FFI cases have been reported in Han Chinese, more so that other Asian regions (including Japan and Korea). The mean age of onset is about 50 years old. EpidemiologyįFI affects both male and females equally with onset typically occurring between the third through sixth decades of life. The sporadic form, termed sporadic fatal insomnia (SFI), presents with similar clinical features as FFI. in 1986, this disorder causes intractable insomnia, dysautonomia and motor system abnormalities. 2.1 Neuro-ophthalmic Symptoms and Signsįatal Familial Insomnia (FFI) is an inherited prion disease produced by a genetic variant of the prion-protein (PrP) gene (PRNP). ![]()
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