{"orpha":364028,"name":"X-linked intellectual disability due to GRIA3 mutations","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":[],"definition":"A rare, genetic, X-linked syndromic intellectual disability disorder characterized by moderate to severe intellectual disability associated with epilepsy, short stature, autistic features and behavioral problems, such as self injury and aggressive outbursts. Observed facial dysmorphism includes brachycephaly, prominent supraorbital ridges, and deep set eyes. Additional variable manifestations include malposition of feet, asthenic habitus, hyporeflexia, bowel occlusions, hydronephrosis, ren arcuatus, delayed motor development and disturbed sleep-wake cycle.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-364028/","orphanet_url":"https://www.orpha.net/en/disease/detail/364028","names":{"fr":{"name":"Déficience intellectuelle liée à l'X par mutations de GRIA3","definition":"Déficience intellectuelle syndromique rare d'origine génétique liée à l'X, caractérisée par une déficience intellectuelle modérée à sévère associée à une épilepsie, une petite taille, des signes de troubles de l'autisme et des troubles du comportement (automutilation et crises d'agressivité). Une dysmorphie faciale est observée, à savoir brachycéphalie, arcades sourcilières proéminentes et yeux profondément situés dans les orbites. Les autres manifestations, inconstantes, comprennent malposition des pieds, habitus asthénique, hyporéflexie, occlusions intestinales, hydronéphrose, rein en fer à cheval, retard de développement moteur et trouble du rythme veille-sommeil."},"de":{"name":"Intelligenzminderung, X-chromosomale, durch GRIA3-Mutationen"},"es":{"name":"Discapacidad intelectual ligada al cromosoma X por mutaciones en el gen GRIA3","definition":"Es un trastorno sindrómico de discapacidad intelectual ligada al cromosoma X, genético y poco frecuente, caracterizado por discapacidad intelectual de moderada a grave asociada a epilepsia, talla baja, rasgos autistas y trastornos de conducta, tales como autolesiones y brotes de agresividad. Se observa dismorfia facial que incluye braquicefalia, crestas supraorbitales prominentes y ojos hundidos. Otras manifestaciones variables asociadas incluyen malposición de los pies, hábito asténico, hiporreflexia, oclusión intestinal, hidronefrosis, riñón en herradura, retraso del desarrollo motor y alteración del ciclo de sueño-vigilia."},"it":{"name":"Disabilità intellettiva legata all'X da mutazione di GRIA3","definition":"È una malattia genetica rara da disabilità intellettiva sindromica legata all'X, caratterizzata da disabilità intellettiva moderata o grave, associata ad epilessia, bassa statura, tratti autistici e problemi comportamentali, compreso l'autolesionismo e crisi di aggressività. I dismorfismi facciali comprendono la brachicefalia, la prominenza delle arcate sopraorbitali e gli occhi infossati. Altri segni clinici variabili sono la malposizione del piede, l'habitus astenico, l'iporeflessia, le occlusioni intestinali, l'idronefrosi, il rene a ferro di cavallo, il ritardo dello sviluppo motorio e i disturbi del ciclo sonno-veglia."},"nl":{"name":"X-gebonden intellectuele achterstand door GRIA3-mutaties","definition":"Een zeldzame, genetische, X-gebonden, syndromale intellectuele stoornis die gekarakteriseerd wordt door matige tot ernstige intellectuele beperking, geassocieerd met epilepsie, kleine gestalte, autistische kenmerken en gedragsproblemen zoals zelfverwonding en agressieve uitbarstingen. Waargenomen faciale dysmorfie omvat brachycefalie, prominente supraorbitale randen, en diepliggende ogen. Bijkomende variabele manifestaties zijn onder meer malpositie van de voeten, asthenische habitus, hyporeflexie, darmocclusies, hydronefrose, ren arcuatus (hoefijzernier), motorische ontwikkelingsachterstand en verstoorde slaap-waakcyclus."},"pt":{"name":"Perturbação do desenvolvimento intelectual devido a mutações GRIA3 ligada ao X"},"pl":{"name":"Niepełnosprawność intelektualna z anomaliami w wyniku mutacji w GRIA3 sprzężona z chromosomem X"},"cs":{"name":"X-vázané mentální postižení způsobené GRIA3 anomáliemi"},"uk":{"name":"Х-зчеплена розумова відсталість, зумовлена мутаціями GRIA3","definition":"A rare, genetic, X-linked syndromic intellectual disability disorder characterized by moderate to severe intellectual disability associated with epilepsy, short stature, autistic features and behavioral problems, such as self injury and aggressive outbursts. Observed facial dysmorphism includes brachycephaly, prominent supraorbital ridges, and deep set eyes. Additional variable manifestations include malposition of feet, asthenic habitus, hyporeflexia, bowel occlusions, hydronephrosis, ren arcuatus, delayed motor development and disturbed sleep-wake cycle."},"zh":{"name":"GRIA3基因突变所致X连锁智力障碍","definition":"本病是一种罕见的、遗传的、X连锁的综合症智力障碍，其特征是中至重度智力残疾与癫痫、矮小、自闭症特征和行为问题，如自我伤害和攻击性发作有关。可观察到的面部畸形包括短头畸形、眶上脊突出和眼睛深陷。其他不同的表现包括脚错位、习惯性虚弱、反射减退、肠闭塞、肾积水、肾弓形、运动发育迟缓和睡眠-觉醒周期紊乱。"},"tr":{"name":"GRIA3 mutasyonları nedeniyle X'e bağlı zihinsel yetersizlik"}},"xrefs":[{"source":"OMIM","code":"300699","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"F72","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"LD90","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0018222","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5191041","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":"GRIA3","name":"glutamate ionotropic receptor AMPA type subunit 3","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"17989220[PMID]","hgnc":"4573","ensembl":"ENSG00000125675","omim":"305915","loci":["Xq25"]}],"genes_via_subtypes":[],"inheritance":["X-linked recessive"],"onset":["Infancy"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":14.0,"area":"Worldwide","status":"Validated","source":"24721225[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_24721225[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-09-09","source":"22124977[PMID]_23637084[PMID]_24721225[PMID]_19449417[PMID]_17989220[PMID]","terms":[{"hpo":"HP:0000750","label":"Delayed speech and language development","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000708","label":"Atypical behavior","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002342","label":"Intellectual disability, moderate","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001533","label":"Slender build","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001328","label":"Specific learning disability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030236","label":"Abnormality of muscle size","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000718","label":"Aggressive behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000729","label":"Autistic behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008936","label":"Axial hypotonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003487","label":"Babinski sign","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002069","label":"Bilateral tonic-clonic seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000248","label":"Brachycephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001320","label":"Cerebellar vermis hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000028","label":"Cryptorchidism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000490","label":"Deeply set eye","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002460","label":"Distal muscle weakness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007655","label":"Eversion of lateral third of lower eyelids","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000297","label":"Facial hypotonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002816","label":"Genu recurvatum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000126","label":"Hydronephrosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001265","label":"Hyporeflexia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001256","label":"Intellectual disability, mild","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010864","label":"Intellectual disability, severe","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001382","label":"Joint hypermobility","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002808","label":"Kyphosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000256","label":"Macrocephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000675","label":"Macrodontia of permanent maxillary central incisor","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000400","label":"Macrotia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000272","label":"Malar flattening","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000303","label":"Mandibular prognathia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000054","label":"Micropenis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001270","label":"Motor delay","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001336","label":"Myoclonus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000189","label":"Narrow palate","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000194","label":"Open mouth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007021","label":"Pain insensitivity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001763","label":"Pes planus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000336","label":"Prominent supraorbital ridges","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000508","label":"Ptosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002719","label":"Recurrent infections","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000817","label":"Reduced eye contact","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006951","label":"Retrocerebellar cyst","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000742","label":"Self-mutilation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006863","label":"Severe expressive language delay","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000322","label":"Short philtrum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004322","label":"Short stature","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000188","label":"Short upper lip","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002360","label":"Sleep abnormality","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006979","label":"Sleep-wake cycle disturbance","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002133","label":"Status epilepticus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012471","label":"Thick vermilion border","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009909","label":"Uplifted earlobe","frequency":"Occasional (29-5%)","criteria":null}]}}