{"orpha":329178,"name":"Congenital muscular dystrophy with intellectual disability and severe epilepsy","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["CDG syndrome type Iu","CDG-Iu","CDG1U","CMD with intellectual disability and severe epilepsy","Carbohydrate deficient glycoprotein syndrome type Iu","Congenital disorder of glycosylation type 1u","Congenital disorder of glycosylation type Iu","DPM2-CDG"],"definition":"A rare, fatal, inborn error of metabolism disorder characterized by respiratory distress and severe hypotonia at birth, severe global developmental delay, early-onset intractable seizures, myopathic facies with craniofacial dysmorphism (trigonocephaly/progressive microcephaly, low anterior hairline, arched eyebrows, hypotelorism, strabismus, small nose, prominent philtrum, thin upper lip, high-arched palate, micrognathia, malocclusion), severe, congenital flexion joint contractures and elevated serum creatine kinase levels. Scoliosis, optic atrophy, mild hepatomegaly, and hypoplastic genitalia may also be associated.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-329178/","orphanet_url":"https://www.orpha.net/en/disease/detail/329178","names":{"fr":{"name":"Dystrophie musculaire congénitale avec déficience intellectuelle et épilepsie sévère","synonyms":["Anomalie congénitale de la glycosylation type 1u","Anomalie congénitale de la glycosylation type Iu","CDG-Iu","CDG1U","CMD avec déficience intellectuelle et épilepsie sévère","DMC avec déficience intellectuelle et épilepsie sévère","DPM2-CDG","Syndrome CDG type Iu","Syndrome des glycoprotéines déficientes en hydrates de carbone type Iu"],"definition":"Erreur innée du métabolisme rare létale, caractérisée par une détresse respiratoire et une hypotonie sévère à la naissance, un sévère retard de développement global, des convulsions réfractaires au traitement à début précoce, un faciès myopathique accompagné d'une dysmorphie craniofaciale (trigonocéphalie/microcéphalie progressive, implantation basse de la ligne antérieure des cheveux, sourcils arqués, hypotélorisme, strabisme, petit nez, philtrum proéminent, lèvre supérieure fine, palais ogival, micrognathie, malocclusion), de sévères contractures congénitales des articulations en flexion et des taux élevés de créatine kinase sérique. Une scoliose, une atrophie optique, une légère hépatomégalie et une hypoplasie des parties génitales peuvent également être associées."},"de":{"name":"Kongenitale Muskeldystrophie mit Intelligenzminderung und schwerer Epilepsie","synonyms":["CDG (Congenital Disorder of Glycosylation) Typ Iu","CDG-Iu","CDG-Syndrom Typ Iu","CDG1U","CMD mit Intelligenzminderung und schwerer Epilepsie","DPM2-CDG","Kohlenhydrat-defizientes Glykoprotein-Syndrom Iu","Kongenitaler Defekt der Glycoproteinbiosynthese Typ Iu"]},"es":{"name":"Distrofia muscular congénita con discapacidad intelectual y epilepsia grave","synonyms":["CDG-Iu","CDG1U","DMC con discapacidad intelectual y epilepsia grave","DPM2-CDG","Síndrome CDG tipo Iu","Síndrome de la glicoproteína deficiente en carbohidrato tipo Iu","Trastorno congénito de la glicosilación tipo 1u","Trastorno congénito de la glicosilación tipo Iu"],"definition":"Es un error innato del metabolismo, fatal y poco frecuente, caracterizado por dificultad respiratoria e hipotonía severa al nacer, retraso global del desarrollo grave, convulsiones intratables de inicio temprano, facies miopática con dismorfia craneofacial (trigonocefalia/microcefalia progresiva, línea anterior de nacimiento del cabello baja, cejas arqueadas, hipotelorismo, estrabismo, nariz pequeña, surco nasolabial prominente, labio superior delgado, paladar alto arqueado, micrognatia, maloclusión), contracturas articulares congénitas de flexión graves y niveles elevados de creatinquinasa sérica. También puede asociarse a escoliosis, atrofia óptica, hepatomegalia leve y genitales hipoplásicos."},"it":{"name":"Distrofia muscolare congenita con disabilità intellettiva ed epilessia grave","synonyms":["CDG-Iu","CDG1U","CMD con deficit cognitivo ed epilessia grave","DPM2-CDG","Disturbo congenito della glicosilazione, tipo Iu","Sindrome CDG, tipo Iu","Sindrome delle glicoproteine carenti in carboidrati, tipo Iu"],"definition":"La distrofia muscolare congenita con disabilità intellettiva ed epilessia grave è un errore congenito del metabolismo raro e letale, caratterizzato da distress respiratorio e grave ipotonia congenita, marcato ritardo dello sviluppo globale, crisi epilettiche ad esordio precoce non trattabili, facies miopatica con dismorfismi craniofacciali (trigonocefalia/ microcefalia progressiva, attaccatura bassa dei capelli sulla fronte, sopracciglia arcuate, ipotelorismo, strabismo, naso piccolo, filtro prominente, labbro superiore sottile, palato ogivale, micrognazia, malocclusione), gravi contratture articolari congenite in flessione e livelli elevati di creatin-chinasi nel siero. Può associarsi a scoliosi, atrofia ottica, lieve epatomegalia ed ipoplasia dei genitali."},"nl":{"name":"Congenitale spierdystrofie met intellectuele achterstand en ernstige epilepsie","synonyms":["CDG-Iu","CDG-syndroom type Iu","CDG1U","CMD met intellectuele achterstand en ernstige epilepsie","Congenitale defecten van de glycosylering type 1u","Congenitale defecten van de glycosylering type Iu","Congenitale glycosylatiestoornis type 1u","Congenitale glycosylatiestoornis type Iu","DPM2-CDG","Koolhydraatdeficiënt glycoproteïne-syndroom type Iu"],"definition":"Congenitale spierdystrofie met intellectuele achterstand en ernstige epilepsie is een zeldzame, fatale, aangeboren stofwisselingsziekte die gekarakteriseerd wordt door ademnood en ernstige hypotonie bij de geboorte, ernstige algehele ontwikkelingsachterstand, onbehandelbare insulten met vroege aanvang, myopathisch gelaat met craniofaciale dysmorfie (trigonocefalie/progressieve microcefalie, lage voorste haarlijn, gebogen wenkbrauwen, hypotelorisme, strabisme, kleine neus, uitgesproken filtrum, dunne bovenlip, hoog gebogen verhemelte, micrognathie, malocclusie), ernstige congenitale flexiecontracturen van gewrichten, en verhoogde gehaltes van creatinekinase in het serum. Scoliose, opticusatrofie, milde hepatomegalie, en hypoplastische genitaliën kunnen ook geassocieerd zijn."},"pt":{"name":"Distrofia muscular congénita com perturbação do desenvolvimento intelectual e epilepsia grave","synonyms":["Síndrome DPM2 -CDG"]},"pl":{"name":"Wrodzona dystrofia mięśniowa z niepełnosprawnością intelektualną i cieżką padaczką","synonyms":["CDG1U","CDG-Iu","DPM2-CDG","Zespół CDG typu Iu","Wrodzone zaburzenie glikozylacji typu 1u","Wrodzone zaburzenie glikozylacji typu Iu","CMD z niepełnosprawnością intelektualną i cieżką padaczką","Zespół obniżonej glikozylacji glikoprotein typu Iu"],"definition":"*Wrodzona dystrofia mięśniowa z niepełnosprawnością intelektualną i ciężką padaczką jest rzadkim, śmiertelnym, wrodzonym błędem metabolicznym; charakteryzuje się niewydolnością oddechową i ciężką hipotonią po urodzeniu, ciężkim całościowym opóźnieniem rozwoju, opornymi na leczenie napadami padaczkowymi o wczesnym początku, miopatyczną twarzą z dysmorfią twarzoczaszki (trigonocefalia/postępujące małogłowie, nisko schodząca przednia linia owłosienia, łukowate brwi, hipoteloryzm, zez, mały nos, wydatna rynienka podnosowa, cienka warga górna, wysokie podniebienie, małożuchwie, wada zgryzu), ciężkimi, wrodzonymi przykurczami zgięciowymi stawów i podwyższonym poziomem kinazy kreatynowej w surowicy. Towarzyszyć mogą również: skolioza, zanik nerwu wzrokowego, łagodne powiększenie wątroby i niedorozwój zewnętrznych narządów płciowych."},"cs":{"name":"Vrozená svalová dystrofie s mentální retardací a těžkou epilepsií","synonyms":["CDG syndrom, typ Iu","CDG-Iu","CDG1U","Syndrom karbohydrátového deficitu glykoproteinu, typ Iu","Vrozená porucha glykosylace, typ Iu","DPM2-CDG","CMD s mentální retardací a těžkou epilepsií"]},"uk":{"name":"Вроджена мязова дистрофія з інтелектуальною недостатністю та важкою формою епілепсії","synonyms":["Вуглеводно-дефіцитний глікопротеїновий синдром типу Iu","Синдром CDG, тип Iu","CDG1U","CDG-Iu","CMD з інтелектуальною недостатністю та тяжкою формою епілепсії","Вроджене порушення глікозилювання типу 1u","Вроджене порушення глікозилювання типу Iu","DPM2-CDG"],"definition":"A rare, fatal, inborn error of metabolism disorder characterized by respiratory distress and severe hypotonia at birth, severe global developmental delay, early-onset intractable seizures, myopathic facies with craniofacial dysmorphism (trigonocephaly/progressive microcephaly, low anterior hairline, arched eyebrows, hypotelorism, strabismus, small nose, prominent philtrum, thin upper lip, high-arched palate, micrognathia, malocclusion), severe, congenital flexion joint contractures and elevated serum creatine kinase levels. Scoliosis, optic atrophy, mild hepatomegaly, and hypoplastic genitalia may also be associated."},"zh":{"name":"先天性肌营养不良伴智障和严重癫痫","synonyms":["糖蛋白碳水化合物缺陷综合征Iu型"],"definition":"先天性肌营养不良伴智力障碍和严重癫痫是一种罕见而致命的先天性代谢紊乱，其特征是呼吸窘迫和出生时严重的张力减退，重度整体发育迟缓，早发难治性癫痫，肌病性筋膜炎伴有颅面部畸形（三角头/进行性小头畸形、前发际线低、弓眉、眼距过窄、斜视、鼻子小、人中突出、薄上唇、高弓腭、小颌畸形、错牙合畸形）、严重的先天性屈曲关节挛缩和血清肌酸激酶水平升高。脊柱侧凸、视神经萎缩、轻度肝肿大和生殖器发育不全也可能相关。"},"tr":{"name":"Zihinsel yetersizlik ve ağır epilepsi ile seyreden doğumsal kas distrofisi","synonyms":["CDG1U","CDG-Iu","DPM2-CDG","CDG sendromu tip Iu","Glikozilasyonun tip 1u doğumsal bozukluğu","Doğumsal glikozilasyon tipi Iu bozukluğu","Zihinsel yetersizlik ve ağır epilepsi ile seyreden CMD","Karbonhidrat eksikliği olan glikoprotein sendromu tip Iu"]}},"xrefs":[{"source":"OMIM","code":"615042","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E77.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C54.2","qualifier":"NTBT","icd_relation":"attributed","validated":true,"icd11_uri":"null"},{"source":"MONDO","code":"0014023","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5190603","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"12416","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":371071,"name":"Congenital disorder of glycosylation with epilepsy as a major feature","classifications":[156,181]},{"orpha":371157,"name":"Congenital disorder of glycosylation with hepatic involvement","classifications":[156,183]},{"orpha":370953,"name":"Congenital muscular dystrophy due to dystroglycanopathy","classifications":[156,181]},{"orpha":309526,"name":"Disorder of multiple glycosylation","classifications":[150,156]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"children":[],"genes":[{"symbol":"DPM2","name":"dolichyl-phosphate mannosyltransferase subunit 2, regulatory","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"23109149[PMID]","hgnc":"3006","ensembl":"ENSG00000136908","omim":"603564","loci":["9q34.11"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":3.0,"area":"Worldwide","status":"Validated","source":"23109149[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-09-19","source":"26453362[PMID]_23109149[PMID]_19901254[PMID]_20301507[PMID]","terms":[{"hpo":"HP:0001999","label":"Abnormal facial shape","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007179","label":"Absent smooth pursuit","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001344","label":"Absent speech","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001321","label":"Cerebellar hypoplasia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005781","label":"Contractures of the large joints","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003236","label":"Elevated circulating creatine kinase concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0200134","label":"Epileptic encephalopathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001508","label":"Failure to thrive","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011169","label":"Generalized clonic seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001290","label":"Generalized hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002123","label":"Generalized myoclonic seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000347","label":"Micrognathia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002058","label":"Myopathic facies","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000938","label":"Osteopenia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002421","label":"Poor head control","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000253","label":"Progressive microcephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003642","label":"Type I transferrin isoform profile","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002518","label":"Abnormal periventricular white matter morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012762","label":"Cerebral white matter atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002002","label":"Deep philtrum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000689","label":"Dental malocclusion","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010851","label":"EEG with burst suppression","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002910","label":"Elevated circulating hepatic transaminase concentration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003241","label":"External genital hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002240","label":"Hepatomegaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000218","label":"High palate","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000601","label":"Hypotelorism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000294","label":"Low anterior hairline","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0040288","label":"Nasogastric tube feeding","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000648","label":"Optic atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001561","label":"Polyhydramnios","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002205","label":"Recurrent respiratory infections","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001976","label":"Reduced antithrombin III activity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002098","label":"Respiratory distress","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003196","label":"Short nose","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000219","label":"Thin upper lip vermilion","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000243","label":"Trigonocephaly","frequency":"Occasional (29-5%)","criteria":null}]}}