{"orpha":508533,"name":"Skeletal dysplasia-T-cell immunodeficiency-developmental delay syndrome","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["EXTL3-related neuro-immuno-skeletal dysplasia syndrome","Neuro-immuno-skeletal dysplasia syndrome due to EXTL3 deficiency"],"definition":"A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by the association of developmental delay, variable intellectual disability, skeletal dysplasia, and in many cases T-cell immunodeficiency and other immunologic abnormalities. Skeletal findings include short stature, anomalies of the long bones, hands and feet, and pelvis, platyspondyly, cervical malformation, and pectus excavatum. Dysmorphic facial features, such as coarse face, hypertelorism, and broad nasal tip, may be present. Additional reported manifestations are seizures, hyperreflexia, nystagmus, and muscular hypotonia, as well as multiple liver cysts.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-508533/","orphanet_url":"https://www.orpha.net/en/disease/detail/508533","names":{"fr":{"name":"Syndrome de dysplasie squelettique-déficit immunitaire à cellules T-retard de développement","synonyms":["Syndrome neuro-immunologique associée à EXTL3","Syndrome neuro-immunologique-dysplasie squelettique par déficit en EXTL3"],"definition":"Anomalies congénitales multiples/syndrome dysmorphique rare d'origine génétique caractérisé par l'association d'un retard de développement, d'une déficience intellectuelle de sévérité variable, d'une dysplasie squelettique et, dans de nombreux cas, d'un déficit de lymphocytes T et d'autres anomalies du système immunitaire. Les anomalies squelettiques sont notamment une petite taille, des anomalies des os longs, des mains et des pieds, du bassin, une platispondylie, une malformation cervicale et un pectus excavatum. Les patients peuvent présenter une dysmorphie faciale (faciès acromégaloïde, hypertélorisme et une pointe nasale large). Les autres signes cliniques rapportés sont des crises convulsives, l'hyperréflexie, le nystagmus, l'hypotonie musculaire, ainsi que de multiples kystes hépatiques."},"de":{"name":"Skelettdysplasie-T-Zell-Immundefekt-Entwicklungsverzögerung-Syndrom","synonyms":["EXTL3-assoziiertes neuro-immuno-skelettales Dysplasie-Syndrom","Neuroimmune Skelettdysplasie durch EXTL3-Defekt"],"definition":"Ein seltenes genetisch bedingtes multiples Dysmorphie-Syndrom, das durch die Assoziation von Entwicklungsverzögerung, variabler Intelligenzminderung, Skelettdysplasie und in vielen Fällen T-Zell-Immunschwäche und anderen immunologischen Anomalien gekennzeichnet ist. Zu den Skelettbefunden gehören Kleinwuchs, Anomalien der Röhrenknochen, der Hände und Füße sowie des Beckens, Platyspondylie, Fehlbildung der Halswirbelsäule und Pectus excavatum. Gesichtsdysmorphien wie ein grobes Gesicht, Hypertelorismus und eine breite Nasenspitze können vorhanden sein. Als weitere Manifestationen werden Krampfanfälle, Hyperreflexie, Nystagmus und Muskelhypotonie sowie multiple Leberzysten berichtet."},"es":{"name":"Síndrome de displasia esquelética-inmunodeficiencia de células T-retraso del desarrollo","synonyms":["Síndrome de displasia neuro-inmuno-esquelética asociada a EXTL3","Síndrome de displasia neuro-inmuno-esquelética por deficiencia de EXTL3"],"definition":"Es un síndrome dismórfico/ de múltiples anomalías congénitas de base genética y poco frecuente caracterizado por la asociación de retraso del desarrollo psicomotor, discapacidad intelectual variable, displasia esquelética y, en muchos casos, inmunodeficiencia de células T y otras alteraciones inmunológicas. Los hallazgos esqueléticos incluyen talla baja, anomalías de los huesos largos, manos, pies y pelvis, platispondilia, malformación cervical y <i>pectus excavatum</i>. También puede asociar rasgos faciales dismórficos, como cara tosca, hipertelorismo y punta nasal ancha. Otras manifestaciones descritas son crisis, hiperreflexia, nistagmo e hipotonía muscular, así como quistes hepáticos múltiples."},"it":{"name":"Sindrome displasia scheletrica-immunodeficienza delle cellule T-ritardo dello sviluppo","synonyms":["Sindrome displasia neuro-immuno-scheletrica correlata a EXTL3","Sindrome displasia neuro-immuno-scheletrica correlata a deficit di EXTL3"],"definition":"Si tratta di una malattia genetica rara da anomalie/dismorfismi congeniti multipli, caratterizzata da ritardo dello sviluppo, disabilità intellettiva di gravità variabile, displasia scheletrica e, spesso, immunodeficienza delle cellule T e altre anomalie immunologiche. Le anomalie scheletriche comprendono la bassa statura, le anomalie delle ossa lunghe, delle mani e dei piedi, e del bacino, la platispondilia, la malformazione del tratto cervicale e il pectus excavatum. I pazienti possono presentare anche dismorfismi facciali (aspetto grossolano del viso, ipertelorismo e punta del naso larga). La malattia può associarsi a crisi epilettiche, iperreflessia, nistagmo, ipotonia muscolare e cisti epatiche multiple."},"nl":{"name":"Skeletdysplasie - T-cel-immuundeficiëntie - ontwikkelingsachterstand-syndroom","synonyms":["EXTL3-gerelateerde neuro-immuno-skeletale dysplasiesyndroom","Neuro-immuno-skeletale dysplasiesyndroom door EXTL3-deficiëntie"],"definition":"Een zeldzaam, genetisch syndroom met multipele congenitale anomalieën/dysmorfie, gekarakteriseerd door de associatie van ontwikkelingsachterstand, variabele intellectuele achterstand, skeletdysplasie, en in vele gevallen T-cel-immuundeficiëntie en andere immunologische afwijkingen. Bevindingen betreffende skelet zijn onder meer kleine gestalte, anomalieen van pijpbeenderen, handen en voeten, en bekken, platyspondylie, cervicale malformatie, en pectus excavatum. Dysmorfe gelaatskenmerken, zoals ruw gelaat, hypertelorisme en brede neuspunt, kunnen aanwezig zijn. Bijkomende manifestaties die werden gerapporteerd, zijn insulten, hyperreflexie, nystagmus, en spierhypotonie, alsook multipele levercysten."},"pt":{"name":"Síndrome de displasia esquelética-imunodeficiência células T-atraso do desenvolvimento"},"pl":{"name":"Zespół dysplazji szkieletowej-niedoboru odporności związanej z limfocytami T-opóźnionego rozwoju","synonyms":["Zespół dysplazji neuro-immuno-szkieletowej związanej z EXTL3","Zespół dysplazji neuro-immuno-szkieletowej wywołanej niedoborem EXTL3"]},"cs":{"name":"Syndrom zahrnující skeletální dysplázii, imunodeficienci T buněk a opoždění vývoje","synonyms":["Syndrom EXTL3-vázané neuroimunoskeletální dysplázie","Syndrom neuroimunoskeletální dysplázie způsobené deficitem EXTL3"]},"uk":{"name":"Синдром скелетної дисплазії-Т-клітинного імунодефіциту-затримки розвитку","synonyms":["Синдром нейро-імуно-скелетної дисплазії, повязаний з EXTL3","Синдром нейро-імуно-скелетної дисплазії внаслідок дефіциту EXTL3"],"definition":"A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by the association of developmental delay, variable intellectual disability, skeletal dysplasia, and in many cases T-cell immunodeficiency and other immunologic abnormalities. Skeletal findings include short stature, anomalies of the long bones, hands and feet, and pelvis, platyspondyly, cervical malformation, and pectus excavatum. Dysmorphic facial features, such as coarse face, hypertelorism, and broad nasal tip, may be present. Additional reported manifestations are seizures, hyperreflexia, nystagmus, and muscular hypotonia, as well as multiple liver cysts."},"zh":{"name":"骨骼发育不良-T细胞免疫缺陷-发育迟缓综合症","synonyms":["EXTL3相关的神经-免疫-骨骼发育不良综合征"]},"tr":{"name":"İskelet displazisi-T hücre immün yetmezlik-gelişme geriliği sendromu","synonyms":["EXTL3 eksikliğine bağlı nöro-immüno-iskelet displazi sendromu","EXTL3-ilişkili nöro-immüno-iskelet displazi sendromu"]}},"xrefs":[{"source":"OMIM","code":"617425","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q87.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"4A01.32","qualifier":"NTBT","icd_relation":"attributed","validated":true,"icd11_uri":"null"},{"source":"MONDO","code":"0033682","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5567899","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93419,"name":"Rare bone disease"},"parents":[{"orpha":611327,"name":"Genetic multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[156]},{"orpha":169349,"name":"Immuno-osseous dysplasia","classifications":[156,195]},{"orpha":102283,"name":"Multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[147,181]},{"orpha":93434,"name":"Spondylodysplastic dysplasia","classifications":[147,156,199]}],"children":[],"genes":[{"symbol":"EXTL3","name":"exostosin like glycosyltransferase 3","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"28132690[PMID]_28148688[PMID]","hgnc":"3518","ensembl":"ENSG00000012232","omim":"605744","loci":["8p21.1"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Antenatal","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":12.0,"area":"Worldwide","status":"Validated","source":"28132690[PMID]_28148688[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_28132690[PMID]_28148688[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2020-01-23","source":"28148688[PMID]_28331220[PMID]_28132690[PMID]","terms":[{"hpo":"HP:0000924","label":"Abnormality of the skeletal system","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001270","label":"Motor delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0004565","label":"Severe platyspondyly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001999","label":"Abnormal facial shape","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000765","label":"Abnormal thorax morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002813","label":"Abnormality of limb bone morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003319","label":"Abnormality of the cervical spine","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002867","label":"Abnormality of the ilium","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008807","label":"Acetabular dysplasia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0045060","label":"Aplasia/hypoplasia involving bones of the extremities","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001156","label":"Brachydactyly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001230","label":"Broad metacarpals","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009768","label":"Broad phalanges of the hand","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004313","label":"Decreased circulating antibody level","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0031381","label":"Decreased lymphocyte proliferation in response to mitogen","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005403","label":"Decreased total T cell count","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0025336","label":"Delayed ability to sit","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003498","label":"Disproportionate short stature","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002007","label":"Frontal bossing","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0032061","label":"Hypereosinophilia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003311","label":"Hypoplasia of the odontoid process","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001265","label":"Hyporeflexia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002808","label":"Kyphosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001888","label":"Lymphopenia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003375","label":"Narrow greater sciatic notch","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010049","label":"Short metacarpal","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003196","label":"Short nose","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009803","label":"Short phalanx of finger","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001328","label":"Specific learning disability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000733","label":"Abnormal repetitive mannerisms","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001344","label":"Absent speech","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000463","label":"Anteverted nares","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008936","label":"Axial hypotonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100865","label":"Broad ischia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000414","label":"Bulbous nose","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005306","label":"Capillary hemangioma","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002341","label":"Cervical cord compression","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008462","label":"Cervical instability","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008445","label":"Cervical spinal canal stenosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002676","label":"Cloverleaf skull","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000280","label":"Coarse facial features","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001363","label":"Craniosynostosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004315","label":"Decreased circulating IgG level","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002850","label":"Decreased circulating total IgM","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0032218","label":"Decreased proportion of CD4-positive T cells","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005415","label":"Decreased proportion of CD8-positive T cells","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000490","label":"Deeply set eye","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002750","label":"Delayed skeletal maturation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005280","label":"Depressed nasal bridge","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009053","label":"Distal lower limb muscle weakness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002307","label":"Drooling","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002987","label":"Elbow flexion contracture","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003051","label":"Enlarged metaphyses","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011166","label":"Focal myoclonic seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000293","label":"Full cheeks","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001290","label":"Generalized hypotonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002197","label":"Generalized-onset seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000212","label":"Gingival overgrowth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002240","label":"Hepatomegaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000085","label":"Horseshoe kidney","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001347","label":"Hyperreflexia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001276","label":"Hypertonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002540","label":"Inability to walk","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003212","label":"Increased circulating IgE concentration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030320","label":"Increased intervertebral space","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004894","label":"Laryngotracheal stenosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009826","label":"Limb undergrowth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002996","label":"Limited elbow movement","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000276","label":"Long face","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003189","label":"Long nose","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000343","label":"Long philtrum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002938","label":"Lumbar hyperlordosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000347","label":"Micrognathia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001634","label":"Mitral valve prolapse","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000160","label":"Narrow mouth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008763","label":"No social interaction","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000194","label":"Open mouth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002179","label":"Opisthotonus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001561","label":"Polyhydramnios","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001830","label":"Postaxial foot polydactyly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001177","label":"Preaxial hand polydactyly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000520","label":"Proptosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006532","label":"Recurrent pneumonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000960","label":"Sacral dimple","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004430","label":"Severe combined immunodeficiency","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011344","label":"Severe global developmental delay","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005619","label":"Thoracolumbar kyphosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Occasional (29-5%)","criteria":null}]}}