{"orpha":485350,"name":"CLCN4-related X-linked intellectual disability syndrome","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Raynaud-Claes syndrome"],"definition":"A rare X-linked syndromic intellectual disability characterized by intellectual disability of variable degree, behavioral anomalies (including autism, mood disorders, obsessive-compulsive behavior, and hetero- and auto-aggression), and epilepsy. Progressive neurological symptoms like movement disorders and spasticity, as well as subtle dysmorphic features have also been reported. Heterozygous females may be as severely affected as males.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-485350/","orphanet_url":"https://www.orpha.net/en/disease/detail/485350","names":{"fr":{"name":"Syndrome de déficience intellectuelle liée à l'X associé à CLCN4","synonyms":["Syndrome de Raynaud-Claes"],"definition":"Déficience intellectuelle rare, liée à l'X, caractérisée par une déficience intellectuelle variable, des troubles du comportement (autisme, troubles de l'humeur, comportement obsessionnel-compulsif et l'hétéro/auto-agréssivité) et l'épilepsie. Des symptômes d'une atteinte neurologique progressive, tels que des troubles du mouvement et une spasticité, ainsi qu'une dysmorphie faciale légère ont également été rapportés. L'atteinte chez les femmes hétérozygotes peut être aussi sévère que chez les hommes."},"de":{"name":"CLCN4-assoziiertes X-chromosomales Intelligenzminderung-Syndrom","definition":"Eine seltene X-chromosomale Form der Intelligenzminderung, die durch intellektuelle Beeinträchtigungen unterschiedlichen Ausmaßes, Verhaltensanomalien (einschließlich Autismus, Stimmungsstörungen, zwanghaftem Verhalten und Hetero- und Autoaggression) und Epilepsie gekennzeichnet ist. Progressive neurologische Symptome wie Bewegungsstörungen und Spastizität sowie subtile dysmorphe Merkmale wurden ebenfalls berichtet. Heterozygote Frauen können ebenso schwer betroffen sein wie Männer."},"es":{"name":"Síndrome de discapacidad intelectual ligada al cromosoma X asociado al gen CLCN4","definition":"Es una discapacidad intelectual sindrómica poco frecuente ligada al cromosoma X que se caracteriza por discapacidad intelectual de grado variable, trastornos de conducta (incluyendo autismo, alteraciones del estado de ánimo, comportamiento obsesivo-compulsivo y hetero- y autoagresión) y epilepsia. También se han descrito síntomas neurológicos progresivos como trastornos del movimiento y espasticidad, así como características dismórficas leves. Las mujeres heterocigotas pueden verse tan gravemente afectadas como los hombres."},"it":{"name":"Disabilità intellettiva legata all'X correlata a CLCN4","definition":"Si tratta di una malattia rara da disabilità intellettiva sindromica legata all'X, caratterizzata da disabilità intellettiva di gravità variabile, anomalie del comportamento (autismo, disturbi dell'umore, comportamento ossessivo-compulsivo, aggressività e autolesionismo) ed epilessia. I pazienti possono presentare anche sintomi neurologici progressivi, come i disturbi del movimento e la spasticità, in associazione con lievi dismorfismi. Nelle femmine eterozigoti la malattia può avere una gravità sovrapponibile a quella dei maschi affetti."},"nl":{"name":"CLCN4-gerelateerde X-gebonden intellectuele achterstand-syndroom","definition":"Een zeldzame X-gebonden syndromale intellectuele achterstand, gekarakteriseerd door intellectuele achterstand met variabele gradaties van ernst, gedragsanomalieën (waaronder autisme, stemmingsstoornissen, obsessief-compulsief gedrag, en hetero- en autoagressie), en epilepsie. Progressieve neurologische symptomen zoals bewegingsstoornissen en spasticiteit, alsook subtiele dysmorfe kenmerken werden ook reeds gerapporteerd. Heterozygote vrouwen kunnen even erg getroffen worden als mannen."},"pt":{"name":"Síndrome de perturbação do desenvolvimento intelectual ligado ao X CLCN4-relacionada"},"pl":{"name":"Zespół niepełnosprawności intelektualnej sprzężony z chromosomem X, związany z CLCN4","synonyms":["Raynaud-Claes syndrome"]},"cs":{"name":"CLCN4-vázaná X-vázaná mentální retardace","synonyms":["Raynaud-Claes syndrome"]},"uk":{"name":"Х-зчеплений синдром інтелектуальної недостатності, повязаний з CLCN4","synonyms":["Синдром Рейно-Клеза"],"definition":"A rare X-linked syndromic intellectual disability characterized by intellectual disability of variable degree, behavioral anomalies (including autism, mood disorders, obsessive-compulsive behavior, and hetero- and auto-aggression), and epilepsy. Progressive neurological symptoms like movement disorders and spasticity, as well as subtle dysmorphic features have also been reported. Heterozygous females may be as severely affected as males."},"zh":{"name":"CLCN4相关X 连锁的智力障碍综合征","synonyms":["Raynaud-Claes syndrome"],"definition":"一种罕见的X染色体连锁综合征性智力障碍，其特征是不同程度的智力障碍、行为异常（包括自闭症、情绪障碍、强迫性强制行为、他人和自身攻击性行为）和癫痫。也有报道称，会出现进行性神经系统症状，如运动障碍和痉挛，以及细微的畸形特征。杂合子女性可能与男性一样受到严重影响。"},"tr":{"name":"CLCN4-ilişkili X'e bağlı zihinsel yetersizlik sendromu","synonyms":["Raynaud-Claes syndrome"]}},"xrefs":[{"source":"OMIM","code":"300114","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"F78.1","qualifier":"NTBT","icd_relation":"attributed","validated":false},{"source":"ICD-11","code":"LD90","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0010250","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0796221","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":538238,"name":"Neurological channelopathy of the central nervous system due to a genetic chloride channel defect","classifications":[156]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"children":[],"genes":[{"symbol":"CLCN4","name":"Cl-/H+ antiporter 4","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"27550844[PMID]","hgnc":"2022","ensembl":"ENSG00000073464","omim":"302910","loci":["Xp22.2"]}],"genes_via_subtypes":[],"inheritance":["X-linked dominant"],"onset":["Childhood","Infancy"],"prevalence":[{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_27550844[PMID]"},{"type":"Cases/families","qualification":"Case(s)","class":null,"value":38.0,"area":"Worldwide","status":"Validated","source":"27550844[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-09-12","source":"27550844[PMID]","terms":[{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002500","label":"Abnormal cerebral white matter morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000708","label":"Atypical behavior","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002120","label":"Cerebral cortical atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002342","label":"Intellectual disability, moderate","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010864","label":"Intellectual disability, severe","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000718","label":"Aggressive behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000739","label":"Anxiety","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000729","label":"Autistic behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002069","label":"Bilateral tonic-clonic seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007302","label":"Bipolar affective disorder","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100704","label":"Cerebral visual impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000722","label":"Compulsive behaviors","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012448","label":"Delayed myelination","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000716","label":"Depression","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011193","label":"EEG with focal spikes","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008947","label":"Floppy infant","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002384","label":"Focal impaired awareness seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011167","label":"Focal tonic seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002020","label":"Gastroesophageal reflux","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002121","label":"Generalized non-motor (absence) seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000752","label":"Hyperactivity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012469","label":"Infantile spasms","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002061","label":"Lower limb spasticity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000256","label":"Macrocephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001336","label":"Myoclonus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006970","label":"Periventricular leukomalacia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002073","label":"Progressive cerebellar ataxia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100716","label":"Self-injurious behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002072","label":"Chorea","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000028","label":"Cryptorchidism","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000023","label":"Inguinal hernia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000276","label":"Long face","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0011800","label":"Midface retrusion","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001763","label":"Pes planus","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000307","label":"Pointed chin","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002317","label":"Unsteady gait","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0006986","label":"Upper limb spasticity","frequency":"Very rare (<4-1%)","criteria":null}]}}