{"orpha":466791,"name":"Macrocephaly-intellectual disability-left ventricular non compaction syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":[],"definition":"Macrocephaly-intellectual disability-left ventricular non compaction syndrome is a rare, genetic, syndromic intellectual disability characterized by motor and cognitive developmental delay with language impairment, macrocephaly, hypotonia, dysmorphic facial features (including long face, slanting palpebral fissures and prominent, flattened nose) and left ventricular noncompaction cardiomyopathy. Patients also present skeletal abnormalities (e.g. scoliosis, finger clinodactyly, pes planus), slender build and shy behavior. Strabismus and various neurological signs (including ataxia, tremor and hyperreflexia) may be associated, as well as epilepsy, autism and MRI findings showing a small cerebellum and abnormalities of the corpus callosum. A phenotypic variant with no cardiac involvement has been reported.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-466791/","orphanet_url":"https://www.orpha.net/en/disease/detail/466791","names":{"fr":{"name":"Syndrome de déficience intellectuelle-macrocéphalie-non-compaction ventriculaire gauche","definition":"Déficience intellectuelle syndromique rare d'origine génétique, caractérisée par un retard de développement moteur et cognitif avec troubles du langage, une macrocéphalie, une hypotonie, une dysmorphie faciale (visage allongé, fentes palpébrales inclinées vers le bas et nez proéminent et aplati) et une cardiomyopathie par non-compaction du ventricule gauche. Les patients présentent également des malformations squelettiques (scoliose, clinodactylie des doigts, pieds plats), une corpulence mince et un comportement timide. Le strabisme et divers signes neurologiques (dont ataxie, tremblements et hyperréflexie) peuvent être associés, de même qu'une épilepsie, l'autisme et un cervelet de petite taille et des anomalies du corps calleux visibles à l'IRM. Une variante phénotypique sans atteinte cardiaque a été rapportée."},"de":{"name":"Makrozephalie-Intelligenzminderung-linksventrikuläre Noncompaction-Kardiomyopathie-Syndrom"},"es":{"name":"Síndrome de macrocefalia-discapacidad intelectual-no compactación del ventrículo izquierdo","definition":"Es una discapacidad intelectual sindrómica, genética y poco frecuente, caracterizada por retraso del desarrollo psicomotor, con trastornos del lenguaje, macrocefalia, hipotonía, rasgos faciales dismórficos (que incluyen cara alargada, fisuras palpebrales inclinadas y nariz prominente y aplanada) y miocardiopatía no compactada del ventrículo izquierdo. Los afectados también presentan anomalías esqueléticas (p. ej. escoliosis, clinodactilia de los dedos de las manos, pies planos), constitución física delgada y comportamiento tímido. Se pueden asociar estrabismo y diversos signos neurológicos (como ataxia, temblor e hiperreflexia), así como epilepsia, autismo y hallazgos en la resonancia magnética mostrando un cerebelo pequeño y anomalías del cuerpo calloso. Se ha descrito una variante fenotípica sin afectación cardíaca."},"it":{"name":"Sindrome da macrocefalia, disabilità intellettiva e ventricolo sinistro non compatto","definition":"La sindrome da macrocefalia, disabilità intellettiva e ventricolo sinistro non compatto è una malattia genetica rara da disabilità intellettiva sindromica, caratterizzata da ritardo dello sviluppo motorio e cognitivo, compromissione del linguaggio, macrocefalia, ipotonia, dismorfismi facciali (viso allungato, rime palpebrali oblique e naso appiattito e prominente) e cardiomiopatia da ventricolo sinistro non compatto. Inoltre, i pazienti presentano anomalie scheletriche (ad esempio scoliosi, clinodattilia delle dita delle mani, piede piatto), corporatura esile e carattere timido. Possono associarsi strabismo, segni neurologici (compresa l'atassia, il tremore e l'iperreflessia), epilessia ed autismo; la RMN evidenzia ipoplasia del cervelletto ed anomalie del corpo calloso. È stata documentata una variante della malattia senza interessamento cardiaco."},"nl":{"name":"Macrocefalie - intellectuele achterstand - non-compactie van linkerventrikel-syndroom","definition":"Macrocefalie - intellectuele achterstand - linkerventrikel non-compactie-syndroom is een zeldzame, genetische, syndromale intellectuele invaliditeit die gekarakteriseerd wordt door motorische en cognitieve ontwikkelingsachterstand met taalstoornis, macrocefalie, hypotonie, dysmorfe gelaatskenmerken (inclusief lang gelaat, hellende ooglidspleten, en uitgesproken en afgeplatte neus) en linkerventrikel non-compactie cardiomyopathie. Patiënten vertonen ook skeletafwijkingen (e.g. scoliose, clinodactylie van vingers, pes planus), tengere lichaamsbouw en verlegen gedrag. Strabisme en verscheidene neurologische tekenen (waaronder ataxie, tremor en hyperreflexie) kunnen geassocieerd zijn, alsook epilepsie, autisme en bevindingen van MRI die een klein cerebellum en afwijkingen van het corpus callosum aantonen. Er werd een fenotypische variant zonder betrokkenheid van het hart gerapporteerd."},"pt":{"name":"Síndrome de macrocefalia-perturbação do desenvolvimento intelectual-não compactação ventricular esquerda"},"pl":{"name":"Zespół wielkogłowia, niepełnosprawności intelektualnej i niescalenia mięśnia lewej komory","definition":"*Zespół wielkogłowia, niepełnosprawności intelektualnej i niescalenia mięśnia lewej komory jest rzadkim, genetycznie uwarunkowanym zespołem niepełnosprawności intelektualnej, który charakteryzuje się opóźnieniem rozwoju ruchowego i poznawczego z zaburzeniami mowy, małogłowiem, hipotonią, dysmorfią twarzy (obejmującą długą twarz, ukośnie ustawione szpary powiekowe i wydatny, spłaszczony nos) i kardiomiopatią z niescalenia mięśnia lewej komory. Obserwuje się również nieprawidłowości szkieletowe (np. skoliozę, klinodaktylię palców, płaskostopie), smukłą budowę ciała i nieśmiałe zachowanie. Mogą towarzyszyć: zez i różne objawy neurologiczne (w tym ataksja, drżenie i wygórowanie odruchów), a także padaczka, autyzm i nieprawidłowości w obrazowaniu MRI, które pokazuje mały móżdżek i nieprawidłowości ciała modzelowatego. Opisano wariant fenotypu bez zajęcia serca."},"cs":{"name":"Syndrom makrocefalie, intelektové nedostatečnosti a nekompaktní levé komory"},"uk":{"name":"Синдром макроцефалії-інтелектуальної недостатності-некомпресії лівого шлуночка","definition":"Macrocephaly-intellectual disability-left ventricular non compaction syndrome is a rare, genetic, syndromic intellectual disability characterized by motor and cognitive developmental delay with language impairment, macrocephaly, hypotonia, dysmorphic facial features (including long face, slanting palpebral fissures and prominent, flattened nose) and left ventricular noncompaction cardiomyopathy. Patients also present skeletal abnormalities (e.g. scoliosis, finger clinodactyly, pes planus), slender build and shy behavior. Strabismus and various neurological signs (including ataxia, tremor and hyperreflexia) may be associated, as well as epilepsy, autism and MRI findings showing a small cerebellum and abnormalities of the corpus callosum. A phenotypic variant with no cardiac involvement has been reported."},"zh":{"name":"巨颅畸形-智力发育迟缓-左心室肌致密化不全综合征","definition":"大头畸形-智力障碍-左心室肌致密化不全综合征是一种罕见的、遗传性的、综合征性智力障碍，其特征是运动和认知发育迟缓，并伴有语言障碍、大头畸形、肌张力低下、畸形面容（包括长脸、眼睑裂开和凸出的扁平鼻）和左心室肌致密化心肌病。患者还表现为骨骼异常（如脊柱侧弯、先天性指侧弯、平足）、体型纤细、行为害羞。可能与斜视和各种神经系统体征（包括共济失调、震颤和反射亢进）有关，以及癫痫、自闭症和MRI结果显示小脑和胼胝体异常。据报道，还有一种不涉及心脏的表型变异。"},"tr":{"name":"Makrosefali-zihinsel yetersizlik-sol ventrikül kompaksiyon olmayan sendrom"}},"xrefs":[{"source":"OMIM","code":"300967","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q87.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0010501","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5569083","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":102283,"name":"Multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[147,181]}],"children":[],"genes":[{"symbol":"NONO","name":"non-POU domain containing octamer binding","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"26571461[PMID]","hgnc":"7871","ensembl":"ENSG00000147140","omim":"300084","loci":["Xq13.1"]}],"genes_via_subtypes":[],"inheritance":["X-linked recessive"],"onset":["Infancy"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":6.0,"area":"Worldwide","status":"Validated","source":"26571461[PMID]_27329731[PMID]_27550220[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_26571461[PMID]_27329731[PMID]_27550220[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-09-11","source":"30773818[PMID]_27550220[PMID]_27329731[PMID]_26571461[PMID]","terms":[{"hpo":"HP:0004482","label":"Relative macrocephaly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001999","label":"Abnormal facial shape","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001711","label":"Abnormal left ventricle morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000739","label":"Anxiety","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002194","label":"Delayed gross motor development","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000750","label":"Delayed speech and language development","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000678","label":"Dental crowding","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006989","label":"Dysplastic corpus callosum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001290","label":"Generalized hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002705","label":"High, narrow palate","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001611","label":"Hypernasal speech","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001256","label":"Intellectual disability, mild","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002751","label":"Kyphoscoliosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000276","label":"Long face","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000272","label":"Malar flattening","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000545","label":"Myopia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000446","label":"Narrow nasal bridge","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000194","label":"Open mouth","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001763","label":"Pes planus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002421","label":"Poor head control","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002033","label":"Poor suck","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000426","label":"Prominent nasal bridge","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000448","label":"Prominent nose","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100962","label":"Shyness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001533","label":"Slender build","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009703","label":"Synostosis involving the 1st metacarpal","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000582","label":"Upslanted palpebral fissure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030872","label":"Abnormal cardiac ventricular function","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000718","label":"Aggressive behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010627","label":"Anterior pituitary hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001631","label":"Atrial septal defect","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000717","label":"Autism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008689","label":"Bilateral cryptorchidism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001321","label":"Cerebellar hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007099","label":"Chiari type I malformation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004209","label":"Clinodactyly of the 5th finger","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007449","label":"Confetti-like hypopigmented macules","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000028","label":"Cryptorchidism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000823","label":"Delayed puberty","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000494","label":"Downslanted palpebral fissures","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010316","label":"Ebstein anomaly of the tricuspid valve","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000286","label":"Epicanthus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001508","label":"Failure to thrive","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002007","label":"Frontal bossing","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002020","label":"Gastroesophageal reflux","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001822","label":"Hallux valgus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007083","label":"Hyperactive patellar reflex","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000316","label":"Hypertelorism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0032009","label":"Infantile constant exotropia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002080","label":"Intention tremor","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001382","label":"Joint hypermobility","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001712","label":"Left ventricular hypertrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0040288","label":"Nasogastric tube feeding","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002870","label":"Obstructive sleep apnea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001643","label":"Patent ductus arteriosus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001655","label":"Patent foramen ovale","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001357","label":"Plagiocephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002465","label":"Poor speech","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007024","label":"Pseudobulbar paralysis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001667","label":"Right ventricular hypertrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000322","label":"Short philtrum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011098","label":"Speech apraxia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002558","label":"Supernumerary nipple","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004684","label":"Talipes valgus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012471","label":"Thick vermilion border","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002684","label":"Thickened calvaria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000219","label":"Thin upper lip vermilion","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000325","label":"Triangular face","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005180","label":"Tricuspid regurgitation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001629","label":"Ventricular septal defect","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000154","label":"Wide mouth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000687","label":"Widely spaced teeth","frequency":"Occasional (29-5%)","criteria":null}]}}