{"orpha":468631,"name":"Microcephalic cortical malformations-short stature due to RTTN deficiency","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":[],"definition":"A rare, genetic, neurodevelopmental disorder with primordial microcephaly characterized by primary microcephaly, moderate to severe intellectual disability, and global developmental delay. Variable brain malformations are common ranging from simplified gyration, to cortical malformations such as pachygyria, polymicrogyria, reduced sulcation and midline defects. Craniofacial dysmorphism (e.g. sloping forehead, high and broad nasal bridge) are related to the primary microcephaly. Short stature is frequently observed, and may be severe.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-468631/","orphanet_url":"https://www.orpha.net/en/disease/detail/468631","names":{"fr":{"name":"Malformations corticales microcéphaliques-petite taille par déficit en RTTN","definition":"Maladie neurodéveloppementale rare d'origine génétique avec microcéphalie primordiale, caractérisée par une microcéphalie primaire, une déficience intellectuelle modérée à sévère et un retard global de développement. Diverses malformations cérébrales sont courantes, allant d'une gyration simplifiée à des malformations corticales, telles qu'une pachygyrie, une polymicrogyrie, un indice de sulcation réduit et des anomalies de la ligne médiane. La dysmorphie craniofaciale (par exemple, front fuyant, pont nasal haut et large) est liée à la microcéphalie primaire. Une petite taille, de forme potentiellement sévère, est fréquemment observée."},"de":{"name":"Mikrozephale kortikale Fehlbildungen mit Kleinwuchs durch RTTN-Defizienz","synonyms":["RTTN-Mangel"],"definition":"Eine seltene neurologische Entwicklungsstörung, die durch primäre Mikrozephalie, mäßige bis schwere Intelligenzminderung und globale Entwicklungsverzögerung gekennzeichnet ist. Häufig sind variable Fehlbildungen des Gehirns, die von vereinfachter Gyration bis hin zu kortikalen Fehlbildungen wie Pachygyrie, Polymikrogyrie, reduzierter Sulkation und Mittellinienfehlern reichen. Kraniofaziale Dysmorphien (z. B. schräge Stirn, hoher und breiter Nasenrücken) stehen im Zusammenhang mit der primären Mikrozephalie. Häufig wird ein Kleinwuchs beobachtet, der schwerwiegend sein kann."},"es":{"name":"Malformaciones corticales microcefálicas-talla baja por deficiencia de RTTN","definition":"Es un trastorno del neurodesarrollo con microcefalia primordial, poco frecuente y de origen genético, caracterizado por microcefalia primaria, discapacidad intelectual de moderada a grave y retraso global del desarrollo. Las malformaciones cerebrales variables son comunes y van desde un patrón de circunvoluciones simplificado hasta malformaciones corticales como la paquigiria, la polimicrogiria, la reducción del patrón de surcos cerebrales y los defectos de la línea media. La dismorfia craneofacial (como frente inclinada, puente nasal alto y ancho) está relacionada con la microcefalia primaria. Con frecuencia se observa talla baja, que puede ser extrema."},"it":{"name":"Malformazioni corticali microcefaliche e bassa statura da deficit di RTTN","definition":"Si tratta di una malattia rara del neurosviluppo, di origine genetica, associata a microcefalia primitiva, caratterizzata da microcefalia, disabilità intellettiva moderata-grave e ritardo dello sviluppo globale. Sono comuni le malformazioni cerebrali di gravità variabile, che comprendono la semplificazione delle circonvoluzioni e le malformazioni corticali (pachigiria, polimicrogiria, riduzione dei solchi e difetti della linea mediana). I dismorfismi craniofacciali (fronte sfuggente, sella nasale prominente e larga) correlano con la microcefalia primitiva. La bassa statura è comune e può essere grave."},"nl":{"name":"Microcefale corticale malformaties - kleine gestalte door RTTN-deficiëntie","definition":"Een zeldzame, genetische neurologische ontwikkelingsstoornis met primordiale microcefalie, gekenmerkt door primaire microcefalie, matige tot ernstige intellectuele achterstand, en algehele ontwikkelingsachterstand. Variabele hersenmalformaties zijn gangbaar, gaande van vereenvoudigde hersenwindingen tot corticale malformaties zoals pachygyrie, polymicrogyrie, verminderde vorming van hersengroeven, en defecten op de middellijn. Craniofaciale dysmorfie (e.g. hellend voorhoofd, hoge en brede neusbrug) is gerelateerd aan de primaire microcefalie. Kleine gestalte wordt vaak waargenomen en kan ernstig zijn."},"pt":{"name":"Malformações corticais microcefálicas-baixa estatura por deficiência RTTN"},"pl":{"name":"Niskorosłość mikrocefaliczna spowodowana niedoborem RTTN","definition":"*Niskorosłość mikrocefaliczna spowodowana niedoborem RTTN jest rzadkim, genetycznie uwarunkowanym zespołem mnogich wad/zespołem dysmorficznym, który charakteryzuje się pierwotnym małogłowiem, istotnie zmniejszonym wzrostem, umiarkowaną lub ciężką niepełnosprawnością intelektualną, całościowym opóźnieniem rozwoju, dysmorfią twarzoczaszki (spadziste czoło, wysoki i szeroki grzbiet nosa) i różnymi wadami mózgu, w tym spłaszczeniem bruzd, pachygyrią (szerokozakrętowość), polimikrogyrią (drobnozakrętowość), zredukowaną liczbą bruzd mózgowych, dysgenezją ciała modzelowatego i zdeformowanymi komorami. Opisywano również wady nerek, obustronny niedosłuch, mnogie przykurcze stawów, istotnie zahamowany rozwój i nieprawidłową zmianę w okolicy krzyżowej powyżej bruzdy pośladkowej."},"cs":{"name":"Primordiální nanismus s mikrocefalií v důsledku deficitu RTTN"},"uk":{"name":"Мікроцефальні вади розвитку кори головного мозку-низькорослість, зумовлена дефіцитом RTTN","definition":"A rare, genetic, neurodevelopmental disorder with primordial microcephaly characterized by primary microcephaly, moderate to severe intellectual disability, and global developmental delay. Variable brain malformations are common ranging from simplified gyration, to cortical malformations such as pachygyria, polymicrogyria, reduced sulcation and midline defects. Craniofacial dysmorphism (e.g. sloping forehead, high and broad nasal bridge) are related to the primary microcephaly. Short stature is frequently observed, and may be severe."},"zh":{"name":"RTTN缺乏相关的小头畸形-原发性矮小症","definition":"RTTN基因缺陷导致的小头先天性侏儒症是一种罕见遗传性、多发性先天性异常/畸形综合征，其特征是原发性小头畸形、身材极度矮小、中度至重度智力障碍、全面发育迟缓、颅面畸形（如：前额倾斜、鼻梁高而宽）和各种脑畸形，包括回带状脑、巨脑回、多小脑回、脑沟减少、胼胝体发育不全和脑室畸形。也有病例有肾脏异常、双侧听力损失、多关节挛缩、严重发育不良和臀皱摺处的头侧端骶骨病变。"},"tr":{"name":"RTTN eksikliğine bağlı mikrosefalik primordiyal cücelik"}},"xrefs":[{"source":"OMIM","code":"614833","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q02","qualifier":"NTBT","icd_relation":"attributed","validated":false},{"source":"MONDO","code":"0018764","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C3553831","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":324761,"name":"Microcephalic primordial dwarfism","classifications":[147,156,181]}],"children":[],"genes":[{"symbol":"RTTN","name":"rotatin","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"26608784[PMID]","hgnc":"18654","ensembl":"ENSG00000176225","omim":"610436","loci":["18q22.2"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":28.0,"area":"Worldwide","status":"Validated","source":"30879067[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"30879067[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-10-18","source":"22939636[PMID]_26940245[PMID)_29967526[PMID]_30121372[PMID]_26608784[PMID]","terms":[{"hpo":"HP:0001999","label":"Abnormal facial shape","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0010864","label":"Intellectual disability, severe","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001511","label":"Intrauterine growth retardation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002828","label":"Multiple joint contractures","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002126","label":"Polymicrogyria","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002465","label":"Poor speech","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001525","label":"Severe failure to thrive","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011344","label":"Severe global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003510","label":"Severe short stature","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000340","label":"Sloping forehead","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005650","label":"2-5 finger cutaneous syndactyly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010705","label":"4-5 finger syndactyly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002518","label":"Abnormal periventricular white matter morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007256","label":"Abnormal pyramidal sign","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004742","label":"Abnormal renal collecting system morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000733","label":"Abnormal repetitive mannerisms","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012294","label":"Abnormality of the occipital bone","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000315","label":"Abnormality of the orbital region","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001274","label":"Agenesis of corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006466","label":"Ankle flexion contracture","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100702","label":"Arachnoid cyst","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007843","label":"Attenuation of retinal blood vessels","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008936","label":"Axial hypotonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007633","label":"Bilateral microphthalmos","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008619","label":"Bilateral sensorineural hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100490","label":"Camptodactyly of finger","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001272","label":"Cerebellar atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001321","label":"Cerebellar hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002059","label":"Cerebral atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006872","label":"Cerebral hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002539","label":"Cortical dysplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001363","label":"Craniosynostosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000028","label":"Cryptorchidism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002247","label":"Duodenal atresia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001260","label":"Dysarthria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000964","label":"Eczematoid dermatitis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002487","label":"Hyperkinetic movements","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001276","label":"Hypertonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007333","label":"Hypoplasia of the frontal lobes","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012110","label":"Hypoplasia of the pons","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000047","label":"Hypospadias","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000601","label":"Hypotelorism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006380","label":"Knee flexion contracture","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001339","label":"Lissencephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006870","label":"Lobar holoprosencephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030260","label":"Microphallus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000308","label":"Microretrognathia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000160","label":"Narrow mouth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006955","label":"Olivopontocerebellar hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000543","label":"Optic disc pallor","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000609","label":"Optic nerve hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001302","label":"Pachygyria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000125","label":"Pelvic kidney","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007165","label":"Periventricular heterotopia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000358","label":"Posteriorly rotated ears","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005487","label":"Prominent metopic ridge","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000426","label":"Prominent nasal bridge","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000520","label":"Proptosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000278","label":"Retrognathia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010767","label":"Sacrococcygeal pilonidal abnormality","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100716","label":"Self-injurious behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009879","label":"Simplified gyral pattern","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002360","label":"Sleep abnormality","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000319","label":"Smooth philtrum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009905","label":"Thin ear helix","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000122","label":"Unilateral renal agenesis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000582","label":"Upslanted palpebral fissure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000431","label":"Wide nasal bridge","frequency":"Occasional (29-5%)","criteria":null}]}}