{"orpha":544469,"name":"PRUNE1-related neurological syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":[],"definition":"A rare genetic syndromic intellectual disability characterized by infantile onset of global developmental delay and profound intellectual disability in association with a heterogeneous spectrum of manifestations, such as features of lower motor neuron disease, hypotonia, spasticity, contractures, seizures, respiratory insufficiency, and optic atrophy, among others. Dysmorphic craniofacial features include microcephaly, tall forehead, bitemporal narrowing, flat nasal bridge, low-set ears, and high-arched palate. Brain imaging may show cerebral and cerebellar atrophy, delayed myelination, and thin corpus callosum.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-544469/","orphanet_url":"https://www.orpha.net/en/disease/detail/544469","names":{"fr":{"name":"Syndrome neurologique associé à PRUNE1","definition":"Déficience intellectuelle syndromique rare d'origine génétique caractérisée par l'apparition infantile d'un retard global de développement et d'une déficience intellectuelle profonde en association avec un spectre hétérogène de manifestations, à savoir signes de la maladie du motoneurone inférieur, hypotonie, spasticité, contractures, convulsions, insuffisance respiratoire et atrophie optique, entre autres. La dysmorphie craniofaciale se caractérise par une microcéphalie, un front haut, un rétrécissement bitemporal, un pont nasal plat, des oreilles d'implantation basse et un palais ogival. Une atrophie cérébrale et cérébelleuse, un retard de myélinisation et un corps calleux fin peuvent s'observer à l'imagerie cérébrale."},"de":{"name":"PRUNE1-assoziiertes neurologisches Syndrom","definition":"Eine genetisch bedingte syndromale Form der Intelligenzminderung, die durch eine globale Entwicklungsverzögerung in der Kindheit und eine tiefgreifende Intelligenzminderung in Verbindung mit einem heterogenen Spektrum von Symptomen gekennzeichnet ist, darunter Merkmale einer Erkrankung der unteren Motoneuronen, Hypotonie, Spastizität, Kontrakturen, Krämpfe, respiratorische Insuffizienz und Optikusatrophie. Zu den dysmorphen kraniofazialen Merkmalen gehören Mikrozephalie, eine hohe Stirn, eine bitemporale Verengung, ein flacher Nasenrücken, tief angesetzte Ohren und ein hochgewölbter Gaumen. Die Bildgebung des Gehirns kann zerebrale und zerebellare Atrophie, verzögerte Myelinisierung und ein dünnes Corpus Callosum zeigen."},"es":{"name":"Síndrome neurológico asociado al gen PRUNE1","definition":"Es una discapacidad intelectual sindrómica poco frecuente caracterizada por la aparición en la lactancia de un retraso global del desarrollo y una profunda discapacidad intelectual en asociación con un espectro heterogéneo de manifestaciones, como rasgos de enfermedad de la motoneurona inferior, hipotonía, espasticidad, contracturas, crisis, insuficiencia respiratoria y atrofia óptica, entre otras. Los rasgos craneofaciales dismórficos incluyen microcefalia, frente alta, estrechamiento bitemporal, puente nasal plano, orejas de implantación baja y paladar alto. La neuroimagen puede mostrar atrofia cerebral y cerebelosa, retraso de la mielinización y adelgazamiento del cuerpo calloso."},"it":{"name":"Malattia neurologica correlata a PRUNE1","definition":"Si tratta di una disabilità intellettiva sindromica rara, di origine genetica, caratterizzata da ritardo dello sviluppo globale ad esordio infantile e disabilità intellettiva grave, associati ad un quadro clinico eterogeneo, che comprende i sintomi della malattia del motoneurone inferiore, l'ipotonia, la spasticità, le contratture, le crisi epilettiche, l'insufficienza respiratoria e l'atrofia ottica. I dismorfismi craniofacciali comprendono la microcefalia, la fronte alta, il restringimento bitemporale, la sella nasale piatta, le orecchie a basso impianto e il palato ogivale. Le neuroimmagini evidenziano atrofia cerebrale e cerebellare, ritardo della mielinizzazione e assottigliamento del corpo calloso."},"nl":{"name":"PRUNE1-gerelateerd neurologisch syndroom","definition":"Een zeldzame, genetische syndromale intellectuele achterstand, gekenmerkt door infantiele aanvang van algehele ontwikkelingsachterstand en zeer ernstige intellectuele achterstand in associatie met een heterogeen spectrum van manifestaties, zoals onder meer kenmerken van aandoening van lagere motorneuronen, hypotonie, spasticiteit, contracturen, insulten, respiratoire insufficiëntie, en opticusatrofie. Dysmorfe craniofaciale kenmerken zijn onder meer microcefalie, hoog voorhoofd, bitemporale vernauwing, platte neusbrug, laagstaande oren, en hoog gebogen gehemelte. Beeldvorming van hersenen toont mogelijk cerebrale en cerebellaire atrofie, vertraagde myelinisatie, en dun corpus callosum."},"pt":{"name":"Síndrome neurológica PRUNE1-relacionada"},"pl":{"name":"Zespół neurologiczny związany z PRINE1"},"cs":{"name":"PRUNE1-vázaný neurologický syndrom"},"uk":{"name":"Неврологічний синдром, повязаний з PRUNE1","definition":"A rare genetic syndromic intellectual disability characterized by infantile onset of global developmental delay and profound intellectual disability in association with a heterogeneous spectrum of manifestations, such as features of lower motor neuron disease, hypotonia, spasticity, contractures, seizures, respiratory insufficiency, and optic atrophy, among others. Dysmorphic craniofacial features include microcephaly, tall forehead, bitemporal narrowing, flat nasal bridge, low-set ears, and high-arched palate. Brain imaging may show cerebral and cerebellar atrophy, delayed myelination, and thin corpus callosum."},"zh":{"name":"PRUNE1基因相关神经综合征"},"tr":{"name":"PRUNE1-ilişkili nörolojik sendrom"}},"xrefs":[{"source":"OMIM","code":"617481","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q07.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0060490","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4479566","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":611327,"name":"Genetic multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[156]},{"orpha":269564,"name":"Genetic syndrome with a central nervous system malformation as a major feature","classifications":[156]},{"orpha":102283,"name":"Multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[147,181]},{"orpha":269531,"name":"Other syndrome with a central nervous system malformation as a major feature","classifications":[147,181]}],"children":[],"genes":[{"symbol":"PRUNE1","name":"prune exopolyphosphatase 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"30556349[PMID]","hgnc":"13420","ensembl":"ENSG00000143363","omim":"617413","loci":["1q21.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":48.0,"area":"Worldwide","status":"Validated","source":"30556349[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_30556349[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2022-09-22","source":"29940663[PMID]_35194938[PMID]_33105479[PMID]","terms":[{"hpo":"HP:0001344","label":"Absent speech","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008936","label":"Axial hypotonia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002020","label":"Gastroesophageal reflux","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002540","label":"Inability to walk","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0010864","label":"Intellectual disability, severe","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001285","label":"Spastic tetraparesis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001272","label":"Cerebellar atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002059","label":"Cerebral atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002169","label":"Clonus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012448","label":"Delayed myelination","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002353","label":"EEG abnormality","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008872","label":"Feeding difficulties in infancy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0032794","label":"Myoclonic seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001357","label":"Plagiocephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002093","label":"Respiratory insufficiency","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0033725","label":"Thin corpus callosum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001776","label":"Bilateral talipes equinovarus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000518","label":"Cataract","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100704","label":"Cerebral visual impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003236","label":"Elevated circulating creatine kinase concentration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011097","label":"Epileptic spasm","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001347","label":"Hyperreflexia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001639","label":"Hypertrophic cardiomyopathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000369","label":"Low-set ears","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000347","label":"Micrognathia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000648","label":"Optic atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001308","label":"Tongue fasciculations","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000488","label":"Retinopathy","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002313","label":"Spastic paraparesis","frequency":"Very rare (<4-1%)","criteria":null}]}}