{"orpha":529665,"name":"Neurodevelopmental delay-seizures-ophthalmic anomalies-osteopenia-cerebellar atrophy syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":["GPAA1-related biosynthesis defect"],"definition":"A rare, genetic, syndromic intellectual disability characterized by global developmental delay, early-onset seizures, cerebellar atrophy, osteopenia, nystagmus and dysmorphic facial features, including bitemporal narrowing, prominent forehead, anteverted nares. Dysarthria, dysmetria, ataxic gait, spasticity and dysmorphic features have also been associated.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-529665/","orphanet_url":"https://www.orpha.net/en/disease/detail/529665","names":{"fr":{"name":"Retard du développement neurologique-épilepsie-anomalies ophtalmiques-ostéopénie-atrophie cérébelleuse","synonyms":["Défaut de biosynthèse associé à GPAA1"],"definition":"Déficience intellectuelle syndromique rare d'origine génétique, caractérisée par un retard global du développement, des crises convulsives précoces, une atrophie cérébelleuse, une ostéopénie, un nystagmus et une dysmorphie faciale, incluant un rétrécissement bitemporal, un front proéminent et des narines antéversées. Une dysarthrie, une dysmétrie, une ataxie locomotrice, une spasticité ont également été associées."},"de":{"name":"Neurologische Entwicklungsverzögerung-Krampfanfälle-Augenanomalien-Osteopenie-zerebelläre Atrophie-Syndrom","synonyms":["GPAA1-assoziierter Biosynthesedefekt"],"definition":"Eine genetisch bedingte syndromale Form der Intelligenzminderung, die durch eine globale Entwicklungsverzögerung, früh einsetzende Krampfanfälle, Kleinhirnatrophie, Osteopenie, Nystagmus und Gesichtsdysmorphien, einschließlich bitemporaler Verschmälerung, prominenter Stirn und antevertierter Nasenflügel, gekennzeichnet ist. Dysarthrie, Dysmetrie, ataktischer Gang, Spastizität und dysmorphe Merkmale wurden ebenfalls festgestellt."},"es":{"name":"Síndrome de retraso del neurodesarrollo-crisis-anomalías oftálmicas-osteopenia-atrofia cerebelosa","synonyms":["Defecto de biosíntesis asociado a GPAA1"],"definition":"Es una discapacidad intelectual sindrómica genética poco frecuente, caracterizada por retraso global del desarrollo, crisis de inicio temprano, atrofia cerebelosa, osteopenia, nistagmo y rasgos faciales dismórficos, incluyendo estrechamiento bitemporal, frente prominente y narinas antevertidas. También se ha asociado a disartria, dismetría, marcha atáxica y espasticidad."},"it":{"name":"Sindrome ritardo del neurosviluppo-crisi epilettiche-anomalie oculari-osteopenia-atrofia cerebellare","definition":"Si tratta di una malattia rara da disabilità intellettiva sindromica, di origine genetica, caratterizzata da ritardo dello sviluppo globale, crisi epilettiche ad esordio precoce, atrofia cerebellare, osteopenia, nistagmo e dismorfismi facciali (restringimento bitemporale, fronte prominente, narici anteverse). Può associarsi a disartria, dismetria, andatura atassica, spasticità e dismorfismi."},"nl":{"name":"Neurologische ontwikkelingsachterstand - insulten - oftalmische anomalieën - osteopenie - cerebellaire atrofie-syndroom","synonyms":["GPAA1-gerelateerd biosynthesedefect"],"definition":"Een zeldzame, genetische, syndromale intellectuele achterstand, gekarakteriseerd door algehele ontwikkelingsachterstand, vroeg optredende insulten, cerebellaire atrofie, osteopenie, nystagmus, en dysmorfe gelaatskenmerken, waaronder bitemporale vernauwing, prominent voorhoofd, en anteversie van de neusgaten. Dysartrie, dysmetrie, ataxische gang, spasticiteit en dysmorfe kenmerken werden ook reeds geassocieerd."},"pt":{"name":"Síndrome de perturbação do neurodesenvolvimento-convulsões-anomalias oftalmológicas-osteopenia-atrofia cerebelosa","synonyms":["Defeito da biossíntese GPAA1-relacionado"]},"pl":{"name":"Zespół atrofii móżdżkowej, osteopenii, wad wzroku, drgawek i opóźnienia neurorozwojowego","synonyms":["GPAA1-related biosynthesis defect"]},"cs":{"name":"Syndrom zahrnující neurovývojové opoždění, záchvaty, oční anomálie, osteopenii a atrofii mozečku","synonyms":["Defekt GPAA1-vázané biosyntézy"]},"uk":{"name":"Синдром затримки нервового розвитку-судом-офтальмологічних аномалій-остеопенії-атрофії мозочка","synonyms":["Дефект біосинтезу, повязаний з GPAA1"],"definition":"A rare, genetic, syndromic intellectual disability characterized by global developmental delay, early-onset seizures, cerebellar atrophy, osteopenia, nystagmus and dysmorphic facial features, including bitemporal narrowing, prominent forehead, anteverted nares. Dysarthria, dysmetria, ataxic gait, spasticity and dysmorphic features have also been associated."},"zh":{"name":"神经发育迟缓-癫痫-眼球异常-骨质疏松-小脑萎缩综合征","synonyms":["GPAA1相关生物合成缺陷"],"definition":"一种罕见的遗传性综合征性智力障碍，其特征是全面发育迟缓、早发性癫痫、小脑萎缩、骨质疏松、眼球震颤和面部畸形，包括双颞部狭窄、前额突出、鼻孔前倾。发音困难、失辨距困难、共济失调步态、痉挛和畸形特征也与此有关。"},"tr":{"name":"Nörogelişme geriliği-nöbetler-oftalmik anomaliler-osteopeni-serebellar atrofi sendromu","synonyms":["GPAA1-ilişkili biyosentez defekti"]}},"xrefs":[{"source":"OMIM","code":"617810","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q87.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0060627","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4540520","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":611327,"name":"Genetic multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[156]},{"orpha":102283,"name":"Multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[147,181]}],"children":[],"genes":[{"symbol":"GPAA1","name":"glycosylphosphatidylinositol anchor attachment 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"29100095[PMID]","hgnc":"4446","ensembl":"ENSG00000197858","omim":"603048","loci":["8q24.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":10.0,"area":"Worldwide","status":"Validated","source":"29100095[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_29100095[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-04-17","source":"29100095[PMID]","terms":[{"hpo":"HP:0002353","label":"EEG abnormality","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000463","label":"Anteverted nares","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002069","label":"Bilateral tonic-clonic seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000455","label":"Broad nasal tip","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001272","label":"Cerebellar atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001321","label":"Cerebellar hypoplasia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000750","label":"Delayed speech and language development","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003698","label":"Difficulty standing","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001260","label":"Dysarthria","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001310","label":"Dysmetria","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002066","label":"Gait ataxia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001288","label":"Gait disturbance","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001290","label":"Generalized hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001347","label":"Hyperreflexia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000316","label":"Hypertelorism","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001256","label":"Intellectual disability, mild","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000545","label":"Myopia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000341","label":"Narrow forehead","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012758","label":"Neurodevelopmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000657","label":"Oculomotor apraxia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000938","label":"Osteopenia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000939","label":"Osteoporosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011220","label":"Prominent forehead","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001337","label":"Tremor","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000648","label":"Optic atrophy","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002133","label":"Status epilepticus","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000505","label":"Visual impairment","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0003155","label":"Elevated circulating alkaline phosphatase concentration","frequency":"Excluded (0%)","criteria":null}]}}