{"orpha":466688,"name":"Severe intellectual disability-corpus callosum agenesis-facial dysmorphism-cerebellar ataxia syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":[],"definition":"A rare genetic neurological disorder characterized by congenital microcephaly, severe intellectual disability, hypertonia at birth lessening with age, ataxia, and specific dysmorphic facial features including hirsutism, low anterior hairline and bitemporal narrowing, arched, thick, and medially sparse eyebrows, long eyelashes, lateral upper eyelids swelling and a skin fold partially covering the inferior eyelids, low-set posteriorly rotated protruding ears, anteverted nares, and a full lower lip. Brain imaging shows partial to almost complete agenesis of the corpus callosum and variable degrees of cerebellar hypoplasia.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-466688/","orphanet_url":"https://www.orpha.net/en/disease/detail/466688","names":{"fr":{"name":"Syndrome de déficience intellectuelle sévère-agénésie du corps calleux-dysmorphie faciale-ataxie cérébelleuse","definition":"Maladie neurologique génétique rare caractérisée par une microcéphalie congénitale, une déficience intellectuelle sévère, une hypertonie à la naissance qui s'atténue avec l'âge, une ataxie et une dysmorphie faciale (hirsutisme, implantation basse de la ligne antérieure des cheveux, rétrécissement bitemporal, sourcils arqués, épais et clairsemés près de la ligne médiane, cils longs, oedème latéral des paupières supérieures et excès cutané recouvrant partiellement la paupière inférieure, oreilles décollées d'implantation basse et inclinées en arrière, narines antéversées et lèvre inférieure pleine. L'imagerie cérébrale met en évidence une agénésie partielle à presque complète du corps calleux et une hypoplasie cérébelleuse de degré variable."},"de":{"name":"Schwere Intelligenzminderung-Corpus callosum-Agenesie-faziale Dysmorphien-zerebelläre Ataxie-Syndrom","definition":"Eine genetisch bedingte seltene neurologische Störung, die durch kongenitale Mikrozephalie, schwere Intelligenzminderung, Hypertonie bei der Geburt, die sich mit zunehmendem Alter abschwächt, Ataxie und spezifische Gesichtsdysmorphien gekennzeichnet ist. Die typischen fazialen Manifestationen umfassen Hirsutismus, niedrige vordere Haarlinie und bitemporale Verschmälerung, gewölbte, dichte und medial spärliche Augenbrauen, lange Wimpern, geschwollene seitliche Oberlider und eine Hautfalte, die die unteren Augenlider teilweise bedeckt, tief angesetzte, nach hinten gedrehte, abstehende Ohren, nach vorne gebogene Nasenlöcher und eine volle Unterlippe. Die Bildgebung des Gehirns zeigt eine teilweise bis fast vollständige Agenesie des Corpus callosum und unterschiedliche Grade der Kleinhirnhypoplasie."},"es":{"name":"Síndrome de discapacidad intelectual grave-agenesia del cuerpo calloso-dismorfia facial-ataxia cerebelosa","definition":"Es un trastorno neurológico, de origen genético y poco frecuente, caracterizado por microcefalia congénita, grave discapacidad intelectual, hipertonía al nacimiento que disminuye con la edad, ataxia y rasgos faciales dismórficos específicos incluyendo hirsutismo, línea anterior de implantación del cabello baja y estrechamiento bitemporal, cejas arqueadas, gruesas y escasas en la zona media, pestañas largas, inflamación del párpado superior lateral acompañado de un pliegue cutáneo que cubre parcialmente los párpados inferiores, orejas prominentes de implantación baja rotadas posteriormente, narinas antevertidas y labio inferior grueso. La neuroimagen muestra agenesia parcial o casi total del cuerpo calloso y diferentes grados de hipoplasia cerebelosa."},"it":{"name":"Sindrome disabilità intellettiva grave-agenesia del corpo calloso-dismorfismi facciali-atassia cerebellare","definition":"Si tratta di una malattia neurologica rara, di origine genetica, caratterizzata da microcefalia congenita, disabilità intellettiva grave, ipertonia congenita che regredisce con l'età, atassia e dismorfismi facciali caratteristici (irsutismo, attaccatura bassa dei capelli sulla fronte, restringimento bitemporale, sopracciglia arcuate, folte, rade nella porzione mediana, ciglia lunghe, gonfiore della porzione laterale della palpebra superiore, plica cutanea che copre parzialmente la palpebra inferiore, orecchie prominenti a basso impianto e ruotate posteriormente, narici anteverse e labbro inferiore carnoso). Le neuroimmagini mostrano una agenesia parziale o pressochè completa del corpo calloso e una ipoplasia cerebellare di gravità variabile."},"nl":{"name":"Ernstige intellectuele achterstand - agenesie van corpus callosum - faciale dysmorfie - cerebellaire ataxie-syndroom","definition":"Een zeldzame, genetische neurologische aandoening, gekarakteriseerd door congenitale microcefalie, ernstige intellectuele beperking, hypertonie bij de geboorte die afneemt met de leeftijd, ataxie, en specifieke dysmorfe gelaatskenmerken, waaronder hirsutisme, lage voorste haarlijn en bitemporale vernauwing, hoog gewelfde, dikke en mediaal schaarse wenkbrauwen, lange wimpers, laterale zelling van bovenste oogleden en een huidplooi die deels de onderste oogleden bedekt, laagstaande, naar achteren gedraaide en afstaande oren, anteversie van neusgaten, en een volle onderlip. Beeldvorming van hersenen toont gedeeltelijke tot nagenoeg volledige agenesie van corpus callosum en variabele gradaties van cerebellaire hypoplasie."},"pt":{"name":"Síndrome de perturbação do desenvolvimento intelectual-agenesia do corpo caloso-dismorfia facial-ataxia cerebelosa"},"pl":{"name":"Zespół znacznejniepełnosprawności intelektualnej, agenezji ciała modzelowatego, dysmorfii twarzy i ataksji móżdżkowej"},"cs":{"name":"Syndrom těžké intelektové nedostatečnosti, ageneze corpus callosum, faciální dysmorfismus a cerebelární ataxie"},"uk":{"name":"Синдром тяжкої розумової відсталості-агенезії мозолистого тіла-дизморфізму обличчя- мозочкової атаксії","definition":"A rare genetic neurological disorder characterized by congenital microcephaly, severe intellectual disability, hypertonia at birth lessening with age, ataxia, and specific dysmorphic facial features including hirsutism, low anterior hairline and bitemporal narrowing, arched, thick, and medially sparse eyebrows, long eyelashes, lateral upper eyelids swelling and a skin fold partially covering the inferior eyelids, low-set posteriorly rotated protruding ears, anteverted nares, and a full lower lip. Brain imaging shows partial to almost complete agenesis of the corpus callosum and variable degrees of cerebellar hypoplasia."},"zh":{"name":"严重智力障碍-胼胝体发育不良-面部畸形-小脑共济失调综合征","definition":"一种罕见的遗传性神经系统疾病，其特点是先天性小头畸形，严重的智力障碍，出生时肌张力过高，随着年龄的增长而减轻，共济失调，以及特定的面部畸形特征，包括多毛症、低前发际线和双颞部狭窄、拱起的浓眉，但中间稀疏、长睫毛、侧上眼睑肿胀、皮褶部分覆盖下眼睑、低位后旋凸耳、鼻梁前倾，下唇饱满。脑影像学显示胼胝体部分至几乎完全缺如，小脑不同程度发育不良。"},"tr":{"name":"Ağır zihinsel yetersizlik-korpus kallozum agenezisi-fasiyal dismorfizm-serebellar ataksi sendromu"}},"xrefs":[{"source":"OMIM","code":"616819","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q87.0","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0014787","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4225193","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":269567,"name":"Genetic syndrome with a cerebellar malformation as a major feature","classifications":[156]},{"orpha":269573,"name":"Genetic syndrome with corpus callosum agenesis/dysgenesis as a major feature","classifications":[156]},{"orpha":102283,"name":"Multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[147,181]},{"orpha":269523,"name":"Syndrome with a cerebellar malformation as a major feature","classifications":[147,181]},{"orpha":199639,"name":"Syndrome with corpus callosum agenesis/dysgenesis as a major feature","classifications":[147,181]}],"children":[],"genes":[{"symbol":"FRMD4A","name":"FERM domain containing 4A","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"25388005[PMID]","hgnc":"25491","ensembl":"ENSG00000151474","omim":"616305","loci":["10p13"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":6.0,"area":"Worldwide","status":"Validated","source":"25388005[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_25388005[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2018-03-05","source":"25388005[PMID]","terms":[{"hpo":"HP:0001344","label":"Absent speech","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001274","label":"Agenesis of corpus callosum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000463","label":"Anteverted nares","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001320","label":"Cerebellar vermis hypoplasia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001510","label":"Growth delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002553","label":"Highly arched eyebrow","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001007","label":"Hirsutism","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001276","label":"Hypertonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010864","label":"Intellectual disability, severe","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002509","label":"Limb hypertonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000527","label":"Long eyelashes","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000294","label":"Low anterior hairline","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000341","label":"Narrow forehead","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002470","label":"Nonprogressive cerebellar ataxia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100540","label":"Palpebral edema","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000358","label":"Posteriorly rotated ears","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011451","label":"Primary microcephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000574","label":"Thick eyebrow","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000179","label":"Thick lower lip vermilion","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002465","label":"Poor speech","frequency":"Occasional (29-5%)","criteria":null}]}}