{"orpha":280763,"name":"Severe intellectual disability and progressive spastic paraplegia","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["AP-4 associated hereditary spastic paraplegia","AP4 deficiency syndrome"],"definition":"A rare complex hereditary spastic paraplegia characterized by an early onset hypotonia that progresses to spasticity, global developmental delay, severe intellectual disability and speech impairment, microcephaly, short stature and dysmorphic features. Patients often become non-ambulatory, and some develop seizures and stereotypic laughter.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-280763/","orphanet_url":"https://www.orpha.net/en/disease/detail/280763","names":{"fr":{"name":"Déficience intellectuelle sévère et paraplégie spastique progressive","synonyms":["Paraplégie spastique héréditaire associée à AP-4","Syndrome de déficit en AP4"],"definition":"Paraplégie spastique complexe rare caractérisée par une hypotonie à début précoce progressant vers une spasticité, un retard de développement global, une déficience intellectuelle sévère, un trouble de la parole, une microcéphalie, une petite taille et une dysmorphie. Les patients perdent souvent l'usage de leurs jambes et certains connaissent des crises convulsives et développent un rire stéréotypé."},"de":{"name":"Intelligenzminderung, schwere, mit progressiver spastischer Paraplegie","synonyms":["AP-4-assoziierte hereditäre spastische Paraplegie","AP4-Mangel-Syndrom"]},"es":{"name":"Discapacidad intelectual grave y paraplejía espástica progresiva","synonyms":["Paraplejía espástica hereditaria asociada a AP-4","Síndrome de deficiencia de AP4"],"definition":"Es una paraplejía espástica compleja poco frecuente caracterizada inicialmente por hipotonía de inicio temprano que evoluciona a espasticidad, retraso global del desarrollo, discapacidad intelectual grave y trastorno del habla, microcefalia, talla baja y características dismórficas. Los afectados pierden, con frecuencia, la capacidad de deambular y algunos desarrollan convulsiones y risas estereotipadas."},"it":{"name":"Deficit cognitivo grave e paraplegia spastica progressiva","synonyms":["Sindrome da deficit di AP4","Paraplegia spastica ereditaria associata all'AP-4"],"definition":"La disabilità intellettiva grave associata a paraplegia spastica progressiva è una paraplegia spastica complessa e rara, caratterizzata da ipotonia ad esordio precoce, che progredisce nella spasticità, nel ritardo dello sviluppo globale, nella disabilità intellettiva grave, nel deficit del linguaggio, nella microcefalia, nella bassa statura e nei dismorfismi. Spesso i pazienti perdono la capacità di deambulare, mentre alcuni sviluppano crisi epilettiche e una risata stereotipata."},"nl":{"name":"Ernstige intellectuele achterstand en progressieve spastische paraplegie","synonyms":["AP-4 geassocieerde hereditaire spastische paraplegie","AP4-deficiëntiesyndroom"],"definition":"Ernstige intellectuele achterstand en progressieve spastische paraplegie is een zeldzame complexe spastische paraplegie, en wordt gekarakteriseerd door vroeg aanvangende hypotonie die evolueert tot spasticiteit, algehele ontwikkelingsachterstand, ernstige intellectuele achterstand en spraakstoornis, microcefalie, kleine gestalte, en dysmorfe kenmerken. Patiënten worden vaak niet-ambulant, en sommigen ontwikkelen insulten en stereotiep gelach."},"pt":{"name":"Perturbação do desenvolvimento intelectual grave e paraplegia espástica progressiva","synonyms":["Síndrome de deficiência de AP4"]},"pl":{"name":"Ciężka niepełnosprawność intelektualna z postępującą paraplegią spastyczną","synonyms":["Zespół niedoboru AP4"],"definition":"*Ciężka niepełnosprawność intelektualna z postępującą paraplegią spastyczną to rzadka złożona paraplegia spastyczna, która charakteryzuje się wcześnie pojawiającą się hipotonią, przechodzącą następnie w spastyczność, całościowym opóźnieniem rozwoju, ciężką niepełnosprawnością intelektualną i zaburzeniami mowy, małogłowiem, niskim wzrostem i cechami dysmorficznymi. Pacjenci często tracą zdolność chodzenia, u niektórych występują napady padaczkowe i stereotypowe napady śmiechu."},"cs":{"name":"Těžká mentální retardace a progresivní spastická paraplegie","synonyms":["Syndrom AP4 deficitu"]},"uk":{"name":"Тяжка розумова відсталість та прогресуюча спастична параплегія","synonyms":["Синдром дефіциту AP4"],"definition":"A rare complex hereditary spastic paraplegia characterized by an early onset hypotonia that progresses to spasticity, global developmental delay, severe intellectual disability and speech impairment, microcephaly, short stature and dysmorphic features. Patients often become non-ambulatory, and some develop seizures and stereotypic laughter."},"zh":{"name":"严重智力障碍和进行性痉挛性截瘫","synonyms":["AP4缺陷综合征"],"definition":"严重智力残疾和进行性痉挛性截瘫是一种罕见的复杂痉挛性截瘫，其特征是早发性肌张力减退，逐渐发展为痉挛性、全面发育迟缓、严重智力残疾和言语障碍、小头畸形、身材矮小和畸形。病人常有走动不能，部分出现癫痫和刻板样笑声。"},"tr":{"name":"Ağır zihinsel yetersizlik ve ilerleyici spastik parapleji","synonyms":["AP4 eksikliği sendromu"]}},"xrefs":[{"source":"OMIM","code":"612936","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"613744","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"614066","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"614067","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"G11.4","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"UMLS","code":"C4755264","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"10999","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":100981,"name":"Autosomal recessive complex spastic paraplegia","classifications":[156,181]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"children":[],"genes":[{"symbol":"AP4B1","name":"adaptor related protein complex 4 subunit beta 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"22290197[PMID]_21620353[PMID]","hgnc":"572","ensembl":"ENSG00000134262","omim":"607245","loci":["1p13.2"]},{"symbol":"AP4E1","name":"adaptor related protein complex 4 subunit epsilon 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"20972249[PMID]_21620353[PMID]","hgnc":"573","ensembl":"ENSG00000081014","omim":"607244","loci":["15q21.2"]},{"symbol":"AP4M1","name":"adaptor related protein complex 4 subunit mu 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"19559397[PMID]","hgnc":"574","ensembl":"ENSG00000221838","omim":"602296","loci":["7q22.1"]},{"symbol":"AP4S1","name":"adaptor related protein complex 4 subunit sigma 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"21620353[PMID]","hgnc":"575","ensembl":"ENSG00000100478","omim":"607243","loci":["14q12"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":15.0,"area":"Worldwide","status":"Validated","source":"21620353[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":"2018-11-05","source":"21620353[PMID]_19559397[PMID]_25552650[PMID]","terms":[{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0010864","label":"Intellectual disability, severe","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0007020","label":"Progressive spastic paraplegia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003487","label":"Babinski sign","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000414","label":"Bulbous nose","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001272","label":"Cerebellar atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002120","label":"Cerebral cortical atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000280","label":"Coarse facial features","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002307","label":"Drooling","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000297","label":"Facial hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001288","label":"Gait disturbance","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001347","label":"Hyperreflexia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002465","label":"Poor speech","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004322","label":"Short stature","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002464","label":"Spastic dysarthria","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002515","label":"Waddling gait","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002518","label":"Abnormal periventricular white matter morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000733","label":"Abnormal repetitive mannerisms","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010803","label":"Everted upper lip vermilion","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000218","label":"High palate","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000341","label":"Narrow forehead","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0025502","label":"Overweight","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001763","label":"Pes planus","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:0100962","label":"Shyness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000154","label":"Wide mouth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008807","label":"Acetabular dysplasia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000646","label":"Amblyopia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002761","label":"Generalized joint hypermobility","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002816","label":"Genu recurvatum","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000486","label":"Strabismus","frequency":"Very rare (<4-1%)","criteria":null}]}}