{"orpha":572013,"name":"Posterior-predominant lissencephaly-broad flat pons and medulla-midline crossing defects syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":[],"definition":"A rare genetic syndrome with a central nervous system malformation as a major feature, characterized by cortical malformations including posterior predominant lissencephaly and diffuse pachygyria, as well as midline crossing defects, thin corpus callosum, dysplastic hippocampi, narrowing of the brainstem with small pons and midbrain, widening of the medulla, and small cerebellum. Clinically, patients present global developmental delay, severe intellectual disability with poor or absent speech, axial hypotonia, and early-onset seizures, among others.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-572013/","orphanet_url":"https://www.orpha.net/en/disease/detail/572013","names":{"fr":{"name":"Syndrome de lissencéphalie à prédominance postérieure-pont et moelle allongée larges et plats-défauts de croisement de la ligne médiane","definition":"Syndrome génétique rare avec malformation du système nerveux central comme manifestation majeure, caractérisé par des malformations corticales, notamment une lissencéphalie à prédominance postérieure et une pachygyrie diffuse, ainsi que par des défauts de croisement de la ligne médiane, un corps calleux aminci, une dysplasie de l'hippocampe, un rétrécissement du tronc cérébral avec un pons et un mésencéphale de petite taille, un élargissement du canal central de la moelle épinière et un petit cervelet. Sur le plan clinique, les patients présentent, en particulier, un retard global de développement, une déficience intellectuelle sévère avec un langage peu développé ou absent, une hypotonie axiale et des crises convulsives d'apparition précoce."},"de":{"name":"Vorwiegend posteriore Lissenzephalie mit breiter flacher Pons und Medulla-Mittelliniendefekt","synonyms":["Lissenzephalie Typ 9 mit komplexer Hirnstammfehlbildung"],"definition":"Ein seltenes genetisches Syndrom mit einer Fehlbildung des Zentralnervensystems als Hauptmerkmal, das durch kortikale Fehlbildungen einschließlich einer vorwiegend posterioren Lissenzephalie und diffuser Pachygyrie sowie Mittellinienfehlbildungen, einem dünnen Corpus callosum, dysplastischen Hippocampi, einer Verengung des Hirnstamms mit kleiner Pons und Mittelhirn, einer Erweiterung der Medulla und einem kleinen Cerebellum gekennzeichnet ist. Klinisch zeigen die Patienten unter anderem eine globale Entwicklungsverzögerung, schwere Intelligenzminderung mit gestörter oder fehlender Sprache, axiale Hypotonie und früh auftretende Krampfanfälle."},"es":{"name":"Síndrome de lisencefalia posterior-puente aplanado y defecto de cruce de la línea media medular","definition":"Es un síndrome genético poco frecuente con una malformación del sistema nervioso central como característica principal, caracterizado por malformaciones corticales que incluyen lisencefalia predominantemente posterior y paquigiria difusa, así como defectos de cruce de la línea media, adelgazamiento del cuerpo calloso, displasia del hipocampo, estrechamiento del tronco encefálico con protuberancia y mesencéfalo pequeños, ensanchamiento del bulbo raquídeo y cerebelo pequeño. Clínicamente, los pacientes presentan retraso global del desarrollo, discapacidad intelectual grave con deficiencia o ausencia del habla, hipotonía axial y crisis de inicio precoz, entre otros."},"it":{"name":"Sindrome lissencefalia prevalentemente posteriore, allargamento e appiattimento del ponte e del midollo, difetti dell'incrocio della linea mediana"},"nl":{"name":"Overwegend posterieure lissencefalie - brede en platte pons en medulla oblongata - defecten van overschrijden van de middellijn-syndroom","definition":"Een zeldzaam genetisch syndroom met een malformatie van centraal zenuwstelsel als belangrijk kenmerk, gekenmerkt door corticale malformaties waaronder posterieur overheersende lissencefalie en diffuse pachygyrie, alsook defecten van kruising van de middellijn, dun corpus callosum, dysplastische hippocampus, vernauwing van hersenstam met kleine pons en middenhersenen, verbreding van medulla oblongata, en klein cerebellum. Klinisch vertonen patiënten onder meer algehele ontwikkelingsachterstand, ernstige intellectuele achterstand met ondermaatse of afwezige spraak, axiale hypotonie, en vroeg optredende insulten."},"pt":{"name":"Síndrome de lisencefalia predominantemente posterior-ponte e medula ampla e achatada-defeitos de decussação da linha média","definition":"Síndrome genética rara com malformações do sistema nervoso central como característica principal, caracterizada por malformações corticais, incluindo lisencefalia predominante posterior e paquigiria difusa, bem como defeitos de cruzamento da linha média, corpo caloso fino, hipocampo displásico, tronco cerebral estreito com ponte e mesencéfalo pequenos, alargamento da medula e cerebelo pequeno. Clinicamente, os doentes apresentam atraso global do desenvolvimento, perturbação do desenvolvimento intelectual grave com linguagem pobre ou ausente, hipotonia axial e convulsões de início precoce, entre outras."},"pl":{"name":"Zespół płaskiego szerokiego mostu pnia mózgu z tylną lizencefalią i wadami poprzecznymi rdzenia w linii środkowej"},"cs":{"name":"Syndrom posteriorně-predominantní lisencefalie, širokého plochého mostu a míchy a defektů křížících střední čáru"},"uk":{"name":"Синдром задньо-переважаючої лісенцефалії-широкого плоского моста та дефектів перетину серединної лінії мозку","definition":"A rare genetic syndrome with a central nervous system malformation as a major feature, characterized by cortical malformations including posterior predominant lissencephaly and diffuse pachygyria, as well as midline crossing defects, thin corpus callosum, dysplastic hippocampi, narrowing of the brainstem with small pons and midbrain, widening of the medulla, and small cerebellum. Clinically, patients present global developmental delay, severe intellectual disability with poor or absent speech, axial hypotonia, and early-onset seizures, among others."},"zh":{"name":"后部-明显无脑回畸形-宽平脑桥延髓-中线交叉缺损综合征"},"tr":{"name":"Posterior-predominant lizensefali-geniş düz pons ve medulla-orta hat geçiş defektleri sendromu"}},"xrefs":[{"source":"OMIM","code":"618325","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618873","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q04.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0032677","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5780029","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":102009,"name":"Classic lissencephaly","classifications":[147,156,181]},{"orpha":730696,"name":"Genetic syndrome with a brainstem malformation as a major feature","classifications":[156]},{"orpha":729519,"name":"Syndrome with a brainstem malformation as a major feature","classifications":[147,181]}],"children":[],"genes":[{"symbol":"CEP85L","name":"centrosomal protein 85L","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"32097630[PMID]","hgnc":"21638","ensembl":"ENSG00000111860","omim":"618865","loci":["6q22.31"]},{"symbol":"MACF1","name":"microtubule actin crosslinking factor 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"30471716[PMID]_24507697[PMID]_24932993[PMID]","hgnc":"13664","ensembl":"ENSG00000127603","omim":"608271","loci":["1p34.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant"],"onset":["Infancy"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":8.0,"area":"Worldwide","status":"Validated","source":"30471716[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_30471716[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2022-09-15","source":"30471716[PMID]_33511591[PMID]","terms":[{"hpo":"HP:0025100","label":"Abnormal hippocampus morphology","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0030301","label":"Abnormality of the anterior commissure","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0007360","label":"Aplasia/Hypoplasia of the cerebellum","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008936","label":"Axial hypotonia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0010864","label":"Intellectual disability, severe","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012758","label":"Neurodevelopmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001302","label":"Pachygyria","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002015","label":"Dysphagia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004305","label":"Involuntary movements","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0033725","label":"Thin corpus callosum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000733","label":"Abnormal repetitive mannerisms","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100704","label":"Cerebral visual impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000324","label":"Facial asymmetry","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002827","label":"Hip dislocation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012469","label":"Infantile spasms","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0032794","label":"Myoclonic seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000011","label":"Neurogenic bladder","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000609","label":"Optic nerve hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Occasional (29-5%)","criteria":null}]}}