{"orpha":466,"name":"Fatal familial insomnia","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["FFI"],"definition":"A rare inherited human prion disease characterized by adult onset of progressive disturbance and loss of circadian rhythms, dysautonomia with increased sympathetic activity, and cognitive impairment with fluctuating vigilance, impaired long-term memory, disorientation, and oneiric states. Motor disturbances include myoclonus, cerebellar ataxia, and pyramidal signs. The disease rapidly leads to a somnolent or comatose state and is typically fatal after 9 or 30 months on average (bimodal course). Neuropathologic examination shows marked neuronal loss and gliosis predominantly in thalamic nuclei and inferior olives, while deposition of abnormal prion protein may be relatively sparse.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-466/","orphanet_url":"https://www.orpha.net/en/disease/detail/466","names":{"fr":{"name":"Insomnie fatale familiale","synonyms":["IFF"],"definition":"Maladie rare à prion humaine héréditaire, caractérisée par la survenue, à l'âge adulte, d'une perturbation progressive et d'une disparition des rythmes circadiens, d'une dysautonomie avec augmentation de l'activité sympathique, de troubles cognitifs à type de fluctuations de la vigilance, de troubles de la mémoire à long terme, de désorientation et d'onirisme. Les troubles moteurs sont une myoclonie, une ataxie cérébelleuse et des signes pyramidaux. La maladie entraîne rapidement un état somnolent ou comateux et est généralement fatale après 9&nbsp;à&nbsp;30&nbsp;mois d'évolution en moyenne (évolution bimodale). L'examen neuropathologique met en évidence une importante perte neuronale et une gliose, principalement au niveau des noyaux thalamiques et de l'olive inférieure, alors que les dépôts de prions anormaux sont relativement rares."},"de":{"name":"Insomnie, familiäre fatale","synonyms":["FFI"],"definition":"Eine seltene vererbte Prionkrankheit des Menschen, die sich im Erwachsenenalter durch eine fortschreitende Störung und einen Verlust der zirkadianen Rhythmen, Dysautonomie mit erhöhter Sympathikusaktivität und kognitive Beeinträchtigung mit schwankender Wachsamkeit, beeinträchtigtem Langzeitgedächtnis, Desorientierung und oneirischen Zuständen auszeichnet. Zu den motorischen Störungen gehören Myoklonus, zerebelläre Ataxie und pyramidale Zeichen. Die Krankheit führt rasch zu einem somnolenten oder komatösen Zustand und endet typischerweise nach durchschnittlich 9 oder 30 Monaten tödlich (bimodaler Verlauf). Die neuropathologische Untersuchung zeigt einen ausgeprägten Neuronenverlust und Gliose vor allem in den thalamischen Kernen und den inferioren Oliven, während die Ablagerung von abnormalem Prionprotein relativ spärlich sein kann."},"es":{"name":"Insomnio familiar fatal","synonyms":["IFF"],"definition":"Es una enfermedad priónica humana hereditaria poco frecuente que se caracteriza por la aparición en la edad adulta de una alteración y pérdida progresiva de los ritmos circadianos, disautonomía con aumento de la actividad simpática y afectación cognitiva con fluctuaciones de la vigilancia, pérdida de la memoria a largo plazo, desorientación y estados oníricos. Las alteraciones motoras incluyen mioclonías, ataxia cerebelosa y signos piramidales. La enfermedad conduce rápidamente a un estado somnoliento o comatoso y suele ser mortal al cabo de 9 ó 30 meses de media (curso bimodal). El examen neuropatológico muestra una marcada pérdida neuronal y gliosis predominantemente en los núcleos talámicos y olivares inferiores, mientras que el depósito de la proteína priónica anómala puede ser relativamente escaso."},"it":{"name":"Insonnia familiare fatale","synonyms":["FFI"],"definition":"Si tratta di una malattia umana rara ereditaria da prioni, che esordisce nell'età adulta con anomalie progressive e perdita dei ritmi circadiani, disautonomia con aumento dell'attività simpatica, e deterioramento cognitivo con vigilanza fluttuante, compromissione della memoria a lungo termine, disorientamento e stati onirici. I disturbi motori comprendono le mioclonie, l'atassia cerebellare e i segni piramidali. La malattia esita rapidamente in uno stato sonnolento o comatoso, e di solito è letale nell'arco di 9-30 mesi (decorso bimodale). L'esame neuropatologico evidenzia una marcata perdita neuronale e gliosi, che interessa prevalentemente il nucleo talamico e olivare inferiore, mentre i depositi di proteina prionica anomala possono essere relativamente scarsi."},"nl":{"name":"Fatale familiale insomnie","synonyms":["FFI"],"definition":"Een zeldzame erfelijke humane prionziekte, gekenmerkt door aanvang in de volwassenheid van progressieve stoornis en verlies van circadiaan ritme, dysautonomie met verhoogde sympathische activiteit, en cognitieve functiestoornis met fluctuerende waakzaamheid, verstoord langetermijngeheugen, desoriëntatie, en dromerige toestand. Motorische stoornissen zijn onder meer myoclonus, cerebellaire ataxie, en piramidale verschijnselen. De ziekte leidt al snel tot somnolentie of coma, en is doorgaans fataal na gemiddeld 9 of 30 maanden (bimodaal verloop). Neuropathologisch onderzoek toont opvallend verlies van neuronen en gliose, hoofdzakelijk in kernen van thalamus en onderste olijfkernen, terwijl depositie van abnormaal prionproteïne relatief schaars kan zijn."},"pt":{"name":"Insónia familiar fatal"},"pl":{"name":"Śmiertelna bezsenność rodzinna","synonyms":["Śmiertlena bezsenność rodzinna"]},"cs":{"name":"Fatální familiární insomnie","synonyms":["FFI"]},"uk":{"name":"Фатальне сімейне безсоння","definition":"A rare inherited human prion disease characterized by adult onset of progressive disturbance and loss of circadian rhythms, dysautonomia with increased sympathetic activity, and cognitive impairment with fluctuating vigilance, impaired long-term memory, disorientation, and oneiric states. Motor disturbances include myoclonus, cerebellar ataxia, and pyramidal signs. The disease rapidly leads to a somnolent or comatose state and is typically fatal after 9 or 30 months on average (bimodal course). Neuropathologic examination shows marked neuronal loss and gliosis predominantly in thalamic nuclei and inferior olives, while deposition of abnormal prion protein may be relatively sparse."},"zh":{"name":"致死性家族性失眠症"},"tr":{"name":"Letal ailesel insomnia"}},"xrefs":[{"source":"OMIM","code":"600072","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"A81.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"8E02.2","qualifier":"E","icd_relation":"specific","validated":true,"icd11_uri":"669154658"},{"source":"MONDO","code":"0010808","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"D034062","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0206042","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"6429","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10072077","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":280400,"name":"Inherited human prion disease","classifications":[156,181]}],"children":[],"genes":[{"symbol":"PRNP","name":"prion protein (Kanno blood group)","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20301407[PMID]","hgnc":"9449","ensembl":"ENSG00000171867","omim":"176640","loci":["20p13"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant"],"onset":["Adult"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":27.0,"area":"Worldwide","status":"Validated","source":"ORPHANET"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2024-11-27","source":"29489284[PMID]_28324299[PMID]_30890351[PMID]_35501502[PMID]","terms":[{"hpo":"HP:0012332","label":"Abnormal autonomic nervous system physiology","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000726","label":"Dementia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0100785","label":"Insomnia","frequency":"Very frequent (99-80%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0001336","label":"Myoclonus","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002071","label":"Abnormality of extrapyramidal motor function","frequency":"Frequent (79-30%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0000739","label":"Anxiety","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0031843","label":"Bradyphrenia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100543","label":"Cognitive impairment","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000716","label":"Depression","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001260","label":"Dysarthria","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002015","label":"Dysphagia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000712","label":"Emotional lability","frequency":"Frequent (79-30%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0009926","label":"Epiphora","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000738","label":"Hallucinations","frequency":"Frequent (79-30%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0000975","label":"Hyperhidrosis","frequency":"Frequent (79-30%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0000822","label":"Hypertension","frequency":"Frequent (79-30%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0006511","label":"Laryngeal stridor","frequency":"Frequent (79-30%)","criteria":"Diagnostic criterion"},{"hpo":"HP:5200044","label":"Reduced attention regulation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:5200360","label":"Short rem sleep","frequency":"Frequent (79-30%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0033687","label":"Short term memory impairment","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010535","label":"Sleep apnea","frequency":"Frequent (79-30%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0006979","label":"Sleep-wake cycle disturbance","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001649","label":"Tachycardia","frequency":"Frequent (79-30%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0012660","label":"Thalamic hypometabolism in FDG PET","frequency":"Frequent (79-30%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0012689","label":"Abnormal pineal melatonin secretion","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007256","label":"Abnormal pyramidal sign","frequency":"Occasional (29-5%)","criteria":"Diagnostic criterion"},{"hpo":"HP:0002019","label":"Constipation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000651","label":"Diplopia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001945","label":"Fever","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003118","label":"Increased circulating cortisol level","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002371","label":"Loss of speech","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001824","label":"Weight loss","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010850","label":"EEG with spike-wave complexes","frequency":"Excluded (0%)","criteria":null}]}}