{"orpha":457395,"name":"Progressive spondyloepimetaphyseal dysplasia-short stature-short fourth metatarsals-intellectual disability syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":[],"definition":"A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay and intellectual disability, progressive spondyloepimetaphyseal dysplasia, short stature, short fourth metatarsals, and dysmorphic craniofacial features (including microcephaly, hypertelorism, epicanthal folds, mild ptosis, strabismus, malar hypoplasia, short nose, depressed nasal bridge, full lips, small, low-set ears, and short neck). Craniosynostosis, generalized hypotonia, as well as asymmetry of the cerebral hemispheres and mild thinning of the corpus callosum on brain imaging have also been described.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-457395/","orphanet_url":"https://www.orpha.net/en/disease/detail/457395","names":{"fr":{"name":"Syndrome de dysplasie spondylo-épimétaphysaire progressive-petite taille-quatrième métatarsien court-déficience intellectuelle","definition":"Anomalies congénitales multiples/syndrome dysmorphique d'origine génétique rare caractérisé par un retard global de développement et une déficience intellectuelle, une dysplasie spondylo-épimétaphysaire progressive, une petite taille, des quatrièmes métatarsiens courts et une dysmorphie craniofaciale (microcéphalie, hypertélorisme, épicanthus, léger ptosis, strabisme, hypoplasie malaire, nez court, pont nasal déprimé, lèvres pleines, petites oreilles d'implantation basse et nuque courte). Une craniosynostose, une hypotonie généralisée, ainsi qu'une asymétrie des hémisphères cérébraux et un léger amincissement du corps calleux identifié à l'imagerie cérébrale ont également été décrits."},"de":{"name":"Progressive spondyloepimetaphysäre Dysplasie-Kleinwuchs-kurze vierte Metatarsalen-Intelligenzminderung-Syndrom","definition":"Ein genetisch bedingtes multiples Dysmorphie-Syndrom mit globaler Entwicklungsverzögerung und Intelligenzminderung, progressiver spondyloepimetaphysärer Dysplasie, Kleinwuchs, kurzem 4. Mittelfußknochen und dysmorphen kraniofazialen Merkmalen (u. a. Mikrozephalie, Hypertelorismus, Epikanthusfalten, leichte Ptosis, Strabismus, Malarhypoplasie, kurze Nase, abgesenkter Nasenrücken, volle Lippen, kleine, tief angesetzte Ohren und kurzer Hals). Kraniosynostose, generalisierte Hypotonie sowie Asymmetrie der Gehirnhälften und eine leichte Ausdünnung des Corpus callosum in der Bildgebung des Gehirns sind ebenfalls beschrieben worden."},"es":{"name":"Síndrome de displasia espondiloepimetafisaria-talla baja-cuartos metatarsianos cortos-discapacidad intelectual progresivo","definition":"Es un síndrome dismórfico/ con múltiples anomalías congénitas, de base genética y poco frecuente, caracterizado por retraso global del desarrollo y discapacidad intelectual, displasia espondiloepimetafisaria progresiva, talla baja, cuartos metatarsianos cortos y rasgos craneofaciales dismórficos (microcefalia, hipertelorismo, pliegues epicánticos, leve ptosis, estrabismo, hipoplasia malar, nariz corta, puente nasal deprimido, labios gruesos, orejas pequeñas y de implantación baja y cuello corto). También se ha descrito craneosinostosis e hipotonía generalizada, así como asimetría de los hemisferios cerebrales y leve adelgazamiento del cuerpo calloso en la neuroimagen."},"it":{"name":"Sindrome displasia spondiloepimetafisaria progressiva-bassa statura-dismorfismi facciali-quarto metatarso corto-disabilità intellettiva","definition":"Si tratta di una malattia genetica rara da anomalie/dismorfismi congeniti multipli, caratterizzata da ritardo dello sviluppo globale e disabilità intellettiva, displasia spondiloepimetafisaria progressiva, bassa statura, accorciamento del quarto metatarso e dismorfismi craniofacciali (microcefalia, ipertelorismo, epicanto, ptosi lieve, strabismo, ipoplasia malare, naso corto, sella nasale infossata, labbra carnose, orecchie piccole e a basso impianto, e collo corto). I pazienti possono presentare anche craniosinostosi, ipotonia generalizzata, asimmetria degli emisferi cerebrali e lieve assottigliamento del corpo calloso evidenti sulle neuroimmagini."},"nl":{"name":"Progressieve spondylo-epimetafysaire dyplasie - kleine gestalte - korte vierde metatarsalen - intellectuele achterstand-syndroom","definition":"Een zeldzaam genetisch syndroom met multipele congenitale anomalieën/dysmorfie, gekarakteriseerd door algehele ontwikkelingsachterstand en intellectuele achterstand, progressieve spondylo-epimetafysaire dysplasie, kleine gestalte, korte vierde metatarsalen, en dysmorfe craniofaciale kenmerken (waaronder microcefalie, hypertelorisme, epicanthusplooien, milde ptose, strabisme, hypoplasie van jukbeenderen, korte neus, ingezakte neusbrug, volle lippen, kleine en laagstaande oren, en korte hals). Craniosynostose, gegeneraliseerde hypotonie, alsook asymmetrie van de cerebrale hemisferen en milde verdunning van het corpus callosum waargenomen bij beeldvorming van de hersenen werden ook reeds beschreven."},"pt":{"name":"Síndrome de displasia espondiloepimetafisária progressiva-baixa estatura-encurtamento do quarto metatarso-perturbação do desenvolvimento intelectual"},"pl":{"name":"Zespół postępującej dysplazji kręgowo-nasadowo-przynasadowej, niskiego wzrostu, krótkich czwartych kości śródstopia i niepełnosprawności intelektualnej"},"cs":{"name":"Syndrom zahrnující progresivní spondyloepimetafyzární dysplázii, malý vzrůst, krátké čtvrté metatarzy a mentální retardaci"},"uk":{"name":"Синдром прогресуючої спондилоепіметафізарної дисплазії-низькорослості-коротких четвертих плеснових кісток-інтелектуальної недостатності","definition":"A rare genetic multiple congenital anomalies/dysmorphic syndrome characterized by global developmental delay and intellectual disability, progressive spondyloepimetaphyseal dysplasia, short stature, short fourth metatarsals, and dysmorphic craniofacial features (including microcephaly, hypertelorism, epicanthal folds, mild ptosis, strabismus, malar hypoplasia, short nose, depressed nasal bridge, full lips, small, low-set ears, and short neck). Craniosynostosis, generalized hypotonia, as well as asymmetry of the cerebral hemispheres and mild thinning of the corpus callosum on brain imaging have also been described."},"zh":{"name":"进行性脊椎干骺端发育不全-身材矮小-第四跖骨短-智力障碍综合征"},"tr":{"name":"İlerleyici spondiloepimetafizyal displazi-kısa boy-kısa dördüncü metatarsal-zihinsel yetersizlik sendromu"}},"xrefs":[{"source":"OMIM","code":"616723","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q87.1","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"LD24.3","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0014748","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5568882","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93419,"name":"Rare bone disease"},"parents":[{"orpha":183570,"name":"Genetic malformation syndrome with short stature","classifications":[156]},{"orpha":611327,"name":"Genetic multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[156]},{"orpha":139021,"name":"Malformation syndrome with short stature","classifications":[147]},{"orpha":102283,"name":"Multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[147,181]},{"orpha":253,"name":"Spondyloepiphyseal dysplasia and spondyloepimetaphyseal dysplasia","classifications":[147,156,199]}],"children":[],"genes":[{"symbol":"RSPRY1","name":"ring finger and SPRY domain containing 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"26365341[PMID]","hgnc":"29420","ensembl":"ENSG00000159579","omim":"616585","loci":["16q13"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":4.0,"area":"Worldwide","status":"Validated","source":"26365341[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_26365341[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-12-16","source":"30063090[PMID]_26365341[PMID]","terms":[{"hpo":"HP:0000598","label":"Abnormality of the ear","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003272","label":"Abnormality of the hip bone","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002815","label":"Abnormality of the knee","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000729","label":"Autistic behavior","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001156","label":"Brachydactyly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001498","label":"Carpal bone hypoplasia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0010579","label":"Cone-shaped epiphysis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001363","label":"Craniosynostosis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002750","label":"Delayed skeletal maturation","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0005280","label":"Depressed nasal bridge","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000286","label":"Epicanthus","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002007","label":"Frontal bossing","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001288","label":"Gait disturbance","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000316","label":"Hypertelorism","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002751","label":"Kyphoscoliosis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000272","label":"Malar flattening","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001270","label":"Motor delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000938","label":"Osteopenia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001845","label":"Overlapping toe","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000926","label":"Platyspondyly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000520","label":"Proptosis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0100864","label":"Short femoral neck","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0004689","label":"Short fourth metatarsal","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000470","label":"Short neck","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003196","label":"Short nose","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0004322","label":"Short stature","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002651","label":"Spondyloepimetaphyseal dysplasia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0010804","label":"Tented upper lip vermilion","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012471","label":"Thick vermilion border","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000766","label":"Abnormal sternum morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000164","label":"Abnormality of the dentition","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004568","label":"Beaking of vertebral bodies","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004209","label":"Clinodactyly of the 5th finger","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002812","label":"Coxa vara","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002967","label":"Cubitus valgus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003521","label":"Disproportionate short-trunk short stature","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005096","label":"Distal femoral bowing","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030293","label":"Fibular metaphyseal irregularity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001290","label":"Generalized hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002857","label":"Genu valgum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005639","label":"Hyperextensible hand joints","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003307","label":"Hyperlordosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0040261","label":"Increased size of nasopharyngeal adenoids","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001256","label":"Intellectual disability, mild","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000369","label":"Low-set ears","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003275","label":"Narrow pelvis bone","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001763","label":"Pes planus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012428","label":"Prominent calcaneus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006461","label":"Proximal femoral epiphysiolysis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001838","label":"Rocker bottom foot","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006863","label":"Severe expressive language delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003026","label":"Short long bone","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010049","label":"Short metacarpal","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004279","label":"Short palm","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003100","label":"Slender long bone","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010585","label":"Small epiphyses","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002944","label":"Thoracolumbar scoliosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030292","label":"Tibial metaphyseal irregularity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008812","label":"Flattened femoral head","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002342","label":"Intellectual disability, moderate","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001377","label":"Limited elbow extension","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001653","label":"Mitral regurgitation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030427","label":"Ossifying fibroma of the jaw","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:0001761","label":"Pes cavus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002677","label":"Small foramen magnum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0004592","label":"Thoracic platyspondyly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001863","label":"Toe clinodactyly","frequency":"Occasional (29-5%)","criteria":null}]}}