{"orpha":452,"name":"X-linked lissencephaly with abnormal genitalia","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":["X-linked lissencephaly with ambiguous genitalia","X-linked lissencephaly-corpus callosum agenesis-genital anomalies syndrome","XLAG (X-linked lissencephaly with abnormal genitalia) syndrome"],"definition":"A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by lissencephaly, agenesis of the corpus callosum and other cerebral structural anomalies, early-onset intractable seizures, and ambiguous genitalia. Consequences of hypothalamic dysfunction, such as disturbed temperature regulation, may be observed. Additional anomalies including dysmorphic craniofacial features have been reported. The disease is fatal in infancy or childhood in males, while female carriers may be unaffected or show a milder phenotype with developmental delay, behavioral abnormalities, and seizures.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-452/","orphanet_url":"https://www.orpha.net/en/disease/detail/452","names":{"fr":{"name":"Lissencéphalie liée à l'X avec anomalies génitales","synonyms":["Lissencéphalie liée à l'X avec ambiguïtés génitales","Syndrome XLAG (Lissencéphalie liée à l'X avec anomalies génitales)","Syndrome de lissencéphalie liée à l'X-agénésie du corps calleux-anomalies génitales"],"definition":"Anomalies congénitales multiples/syndrome dysmorphique, d'origine génétique, caractérisé par une lissencéphalie, une agénésie du corps calleux accompagnée d'autres anomalies structurelles du cerveau, une épilepsie réfractaire à début précoce et une ambiguïté sexuelle. Le dysfonctionnement hypothalamique peut avoir des conséquences, telles qu'une perturbation de la régulation de la température. D'autres anomalies, dont une dysmorphie craniofaciale, ont été rapportées. La maladie est létale pendant la petite enfance ou l'enfance chez les garçons, alors que les filles porteuses de la mutation pathogène peuvent ne pas être affectées ou ne présenter qu'un phénotype léger, à type de retard de développement, de troubles du comportement et d'épilepsie."},"de":{"name":"X-chromosomale Lissenzephalie mit Genitalanomalien","synonyms":["Lissenzephalie, X-chromosomale - Corpus-callosum-Agenesie - Genitalanomalien","XLAG-Syndrom"],"definition":"Die X-chromosomale Lissenzephalie mit abnormen Genitalien (XLAG) ist eine schwere neurologische Störung und betrifft nur genetisch männliche Individuen. Zu den Symptomen gehören (i) eine Lissenzephalie mit postero-anteriorem Gradient und nur leichter Verbreiterung der Hirnrinde, (ii) Agenesie des Corpus callosum, (iii) schwere Epilepsie mit Beginn im Neugeborenenalter, (iv) Dysfunktion des Hypothalamus mit gestörter Temperaturregulation, (v) intermediäres Genitale mit Mikropenis und Kryptorchismus."},"es":{"name":"Lisencefalia ligada al cromosoma X con anomalías genitales","synonyms":["Lisencefalia ligada al cromosoma X con genitales ambiguos","Lisencefalia ligada al cromosoma X-agenesia del cuerpo calloso-anomalías genitales","Síndrome XLAG (lisencefalia ligada al cromosoma X con anomalías genitales)"],"definition":"Es un síndrome dismórfico/ de anomalías congénitas múltiples, de origen genético y poco frecuente, caracterizado por lisencefalia, agenesia del cuerpo calloso y otras anomalías estructurales cerebrales, crisis epilépticas intratables de inicio temprano y genitales ambiguos. Las consecuencias de la disfunción hipotalámica, como la alteración de la regulación de la temperatura, son patentes. También se han descrito anomalías adicionales que incluyen rasgos craneofaciales dismórficos. La enfermedad es mortal en la lactancia o la infancia en varones, mientras que las mujeres portadoras pueden no verse afectadas o mostrar un fenotipo más leve con retraso del desarrollo, trastornos de la conducta y crisis."},"it":{"name":"Lissencefalia legata all'X con genitali ambigui","synonyms":["Lissencefalia legata all'X - agenesia del corpo calloso - anomalie genitali","Lissencefalia legata all'X con ambiguità genitale","Sindrome XLAG (lissencefalia legata all'X con genitali ambigui)"]},"nl":{"name":"X-gebonden lissencefalie met abnormale genitaliën","synonyms":["X-gebonden lissencefalie - agenesie van het corpus callosum - genitale anomalieën-syndroom","X-gebonden lissencefalie met ambigue genitaliën","XLAG (X-gebonden lissencefalie met abnormale genitaliën)-syndroom"],"definition":"Een zeldzaam genetisch syndroom met multipele congenitale anomalieën/dysmorfie, gekenmerkt door lissencefalie, agenesie van corpus callosum en andere cerebrale structurele anomalieën, vroeg optredende refractaire insulten, en ambigue genitaliën. Mogelijk worden gevolgen van disfunctie van hypothalamus waargenomen, zoals verstoorde regulatie van lichaamstemperatuur. Bijkomende anomalieën, waaronder dysmorfe craniofaciale kenmerken, werden reeds gerapporteerd. De ziekte is fataal in de zuigelingentijd of kindertijd bij mannen, terwijl vrouwelijke dragers niet aangetast worden of een milder fenotype vertonen met ontwikkelingsachterstand, gedragsstoornissen en insulten."},"pt":{"name":"Lisencefalia ligada ao X com anomalias genitais","synonyms":["Lisencefalia ligada ao X-agenesia do corpo caloso-anomalias genitais"],"definition":"A lisencefalia com anomalias genitais ligada ao X (XLAG) é uma doença neurológica grave que só se manifesta em indivíduos genotipicamente masculinos e inclui lisencefalia com gradiente posterior-a-anterior e aumento apenas moderado na espessura do córtex, corpo caloso ausente, epilepsia grave de apresentação neonatal, disfunção do hipotálamo incluindo defeito da regulação da temperatura, e genitais ambíguos com micropénis e criptorquidia. A XLAG difere consideravelmente da lisencefalia clássica, uma vez que a espessura cortical resultante é de apenas 6-7 milímetros na XLAG, ao invés de 15-20 mm visto na lisencefalia clássica devido a mutações nos genes <i> PAFAH1B1 </ i> ou <i> DCX < / i>."},"pl":{"name":"Lizencefalia sprzężona z chromosomem X z nieprawidłowymi narządami płciowymi","synonyms":["Lizencefalia sprzężona z chromosomem X - agnezja ciała modzelowatego - anomalie narządów płciowych","Lizencefalia sprzężona z chromosomem X z obojnaczymi narządami płciowymi","Zespół XLAG (Lizencefalia sprzężona z chromosomem X z nieprawidłowymi narządami płciowymi)"]},"cs":{"name":"X-vázaná lisencefalie s abnormálními genitáliemi","synonyms":["Syndrom zahrnující X-vázanou lisencefalii, agenezi corpus callosum a anomálie genitálu","XLAG (X-vázaná lisencefalie s abnormálními genitáliemi) syndrom","X-vázaná lisencefalie s nejednoznačnými genitáliemi"]},"uk":{"name":"Х-зчеплена ліссенцефалія з аномальними геніталіями","synonyms":["Синдром XLAG (Х-зчеплена ліссенцефалія з аномальними геніталіями)","Х-зчеплена ліссенцефалія з неоднозначними геніталіями","Х-зчеплений синдром агенезії ліссенцефалії-генезії мозолистого тіла-генітальних аномалій"],"definition":"A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by lissencephaly, agenesis of the corpus callosum and other cerebral structural anomalies, early-onset intractable seizures, and ambiguous genitalia. Consequences of hypothalamic dysfunction, such as disturbed temperature regulation, may be observed. Additional anomalies including dysmorphic craniofacial features have been reported. The disease is fatal in infancy or childhood in males, while female carriers may be unaffected or show a milder phenotype with developmental delay, behavioral abnormalities, and seizures."},"zh":{"name":"X连锁无脑回畸形伴外生殖器畸形","synonyms":["X-连锁无脑回畸形-胼胝体发育迟缓-生殖器异常综合征"]},"tr":{"name":"Anormal genital ile seyreden X'e bağlı lizensefali","synonyms":["Belirsiz cinsel organla ile seyreden X'e bağlı lizensefali","XLAG (anormal genital yapıya sahip X'e bağlı lizensefali) sendromu","X'e bağlı lizensefali-korpus kallozum agenezisi-genital anomaliler sendromu"]}},"xrefs":[{"source":"OMIM","code":"300215","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q04.3","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"LD20.1","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"714984818"},{"source":"MONDO","code":"0010268","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C564563","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C1846171","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"12491","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":423655,"name":"ARX-related encephalopathy-brain malformation spectrum","classifications":[147,156,181,185]},{"orpha":102010,"name":"Other syndrome with lissencephaly as a major feature","classifications":[147,156,181]},{"orpha":98087,"name":"Syndrome with 46,XY difference of sex development","classifications":[147,156,185,193]}],"children":[],"genes":[{"symbol":"ARX","name":"aristaless related homeobox","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"12379852[PMID]_12874405[PMID]","hgnc":"18060","ensembl":"ENSG00000004848","omim":"300382","loci":["Xp21.3"]}],"genes_via_subtypes":[],"inheritance":["X-linked recessive"],"onset":["Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Family(ies)","class":null,"value":30.0,"area":"Worldwide","status":"Validated","source":"17480217[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"Unknown","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_17480217[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2016-06-01","source":null,"terms":[{"hpo":"HP:0001274","label":"Agenesis of corpus callosum","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000062","label":"Ambiguous genitalia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000028","label":"Cryptorchidism","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008736","label":"Hypoplasia of penis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001302","label":"Pachygyria","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001522","label":"Death in infancy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000966","label":"Hypohidrosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002024","label":"Malabsorption","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002251","label":"Aganglionic megacolon","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001738","label":"Exocrine pancreatic insufficiency","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000347","label":"Micrognathia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001643","label":"Patent ductus arteriosus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011220","label":"Prominent forehead","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001629","label":"Ventricular septal defect","frequency":"Occasional (29-5%)","criteria":null}]}}