{"orpha":521390,"name":"Spastic paraplegia-intellectual disability-nystagmus-obesity syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":["SINO syndrome"],"definition":"A rare genetic neurological disorder characterized by the association of congenital spastic paraplegia with global developmental delay and intellectual disability, ophthalmologic abnormalities (including nystagmus, reduced visual acuity, or hypermetropia), and obesity. Additional manifestations are brachyplagiocephaly and dysmorphic facial features. Brain imaging may show dilated ventricles, abnormal myelination, and mild generalized atrophy. Homozygous loss-of-function variants of <i>KIDINS220</i> associated with a fetal lethal phenotype with ventriculomegaly and limb contractures have been reported.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-521390/","orphanet_url":"https://www.orpha.net/en/disease/detail/521390","names":{"fr":{"name":"Syndrome de paraplégie spastique-déficience intellectuelle-nystagmus-obésité","synonyms":["Syndrome SINO"],"definition":"Maladie neurologique génétique rare caractérisée par l'association d'une paraplégie spastique congénitale avec un retard global de développement, une déficience intellectuelle, des anomalies ophtalmologiques (notamment un nystagmus, une baisse de l'acuité visuelle ou une hypermétropie) et l'obésité. On observe par ailleurs une brachyplagiocéphalie et une dysmorphie faciale. L'IRM peut mettre en évidence une dilatation des ventricules, une myélinisation anormale et une légère atrophie généralisée. Des variants homozygotes avec une perte de fonction de <i>KIDINS220</i> associés à un phénotype entraînant le décès du foetus avec une ventriculomégalie et des contractures des membres ont également été rapportés."},"de":{"name":"Spastische Paraplegie-Intelligenzminderung-Nystagmus-Adipositas-Syndrom","synonyms":["SINO-Syndrom"],"definition":"Eine genetisch bedingte neurologische Störung, die durch eine angeborene spastische Paraplegie in Verbindung mit einer globalen Entwicklungsverzögerung und Intelligenzminderung, ophthalmologischen Anomalien (einschließlich Nystagmus, verminderter Sehschärfe oder Hypermetropie) und Adipositas gekennzeichnet ist. Weitere Erscheinungsformen sind Brachyplagiozephalie und Gesichtsdysmorphien. Die zerebrale Bildgebung kann erweiterte Ventrikel, eine abnorme Myelinisierung und eine leichte generalisierte Atrophie zeigen. Es wurde eine homozygote Loss-of-function-Variante im <i>KIDINS220</i>-Gen beschrieben, die mit einem letalen fetalen Phänotyp mit Ventrikulomegalie und Gliedmaßenkontrakturen einhergeht."},"es":{"name":"Síndrome de paraplejía espástica-discapacidad intelectual-nistagmo-obesidad","synonyms":["Síndrome SINO"],"definition":"Es un trastorno neurológico, de origen genético y poco frecuente, caracterizado por la asociación de paraparesia espástica congénita acompañada de un retraso global del desarrollo y discapacidad intelectual, anomalías oftalmológicas (incluyendo nistagmo, disminución de la agudeza visual o hipermetropía) y obesidad. Otras manifestaciones adicionales son braquiplagiocefalia y rasgos faciales dismórficos. La neuroimagen puede mostrar dilatación ventricular, mielinización anómala y una leve atrofia generalizada. Se han descrito variantes de pérdida de función en homocigosis en el gen <i>KIDINS220</i> asociadas a un fenotipo letal fetal con ventriculomegalia y contracturas de las extremidades."},"it":{"name":"Sindrome paraplegia spastica-disabilità intellettiva-nistagmo-obesità","synonyms":["Sindrome SINO"],"definition":"Si tratta di una malattia neurologica rara, di origine genetica, caratterizzata da paraplegia spastica congenita, ritardo dello sviluppo globale, disabilità intellettiva, anomalie oculari (nistagmo, riduzione dell'acuità visiva o ipermetropia) e obesità. I pazienti possono presentare anche brachi-plagiocefalia e dismorfismi facciali. Le neuroimmagini mostrano ventricoli dilatati, anomalie della mielinizzazione e lieve atrofia generalizzata. Sono state descritte alcune varianti omozigoti con perdita di funzione di KIDINS220, associate ad un fenotipo fetale letale con ventricolomegalia e contratture degli arti."},"nl":{"name":"Spastische paraplegie - intellectuele achterstand - nystagmus - obesitas-syndroom","synonyms":["SINO-syndroom"],"definition":"Een zeldzame genetische, neurologische aandoening, gekarakteriseerd door de associatie van congenitale spastische paraplegie met algehele ontwikkelingsachterstand en intellectuele beperking, oftalmologische afwijkingen (waaronder nystagmus, verminderde gezichtsscherpte, of hypermetropie), en obesitas. Bijkomende manifestaties zijn brachyplagiocefalie en dysmorfe gelaatskenmerken. Beeldvorming van hersenen toont mogelijk gedilateerde ventrikels, abnormale myelinisatie, en milde gegeneraliseerde atrofie. Homozygote varianten met functieverlies van KIDINS220 geassocieerd met een foetaal letaal fenotype met ventriculomegalie en contracturen van ledematen werden reeds gerapporteerd."},"pt":{"name":"Síndrome de paraplegia espástica-perturbação do desenvolvimento intelectual-nistagmo-obesidade"},"pl":{"name":"Zespół paraplegii spastycznej- niepełnosprawności intelekturalnej-zeza-otyłości","synonyms":["Zespół SINO"]},"cs":{"name":"Syndrom zahrnující spastickou paraplegii, mentální retardaci, nystagmus a obezitu","synonyms":["Syndrom SINO"]},"uk":{"name":"Синдром спастичної параплегії-інтелектуальної недостатності-ністагму-ожиріння","synonyms":["Синдром SINO"],"definition":"A rare genetic neurological disorder characterized by the association of congenital spastic paraplegia with global developmental delay and intellectual disability, ophthalmologic abnormalities (including nystagmus, reduced visual acuity, or hypermetropia), and obesity. Additional manifestations are brachyplagiocephaly and dysmorphic facial features. Brain imaging may show dilated ventricles, abnormal myelination, and mild generalized atrophy. Homozygous loss-of-function variants of <i>KIDINS220</i> associated with a fetal lethal phenotype with ventriculomegaly and limb contractures have been reported."},"zh":{"name":"痉挛性截瘫-智力障碍-眼球震颤-肥胖综合症","synonyms":["SINO syndrome"],"definition":"一种罕见的遗传性神经系统疾病，其特点是先天性痉挛性截瘫伴有全面发育迟缓和智力障碍、眼科异常（包括眼球震颤、视力敏锐度减退或远视眼）和肥胖。其他表现还有短斜头畸形和面部畸形。脑影像学检查可显示心室扩张、髓鞘形成异常和轻度全身萎缩。据报道，KIDINS220基因的纯合功能缺失变异与胎儿致死表型有关，伴有巨脑室和肢体挛缩。"},"tr":{"name":"Spastik parapleji-zihinsel yetersizlik-nistagmus-obezite sendromu","synonyms":["SINO sendromu"]}},"xrefs":[{"source":"OMIM","code":"617296","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"G11.4","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0015007","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4284592","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":100979,"name":"Autosomal dominant complex spastic paraplegia","classifications":[156,181]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]},{"orpha":240371,"name":"Syndromic obesity","classifications":[147,156,193]}],"children":[],"genes":[{"symbol":"KIDINS220","name":"kinase D interacting substrate 220","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"27005418[PMID]","hgnc":"29508","ensembl":"ENSG00000134313","omim":"615759","loci":["2p25.1"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant"],"onset":["Antenatal","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":4.0,"area":"Worldwide","status":"Validated","source":"27005418[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_27005418[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2018-11-26","source":"27005418[PMID]","terms":[{"hpo":"HP:0011400","label":"Abnormal CNS myelination","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000490","label":"Deeply set eye","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002194","label":"Delayed gross motor development","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0025312","label":"Esophoria","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000540","label":"Hypermetropia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001513","label":"Obesity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001357","label":"Plagiocephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007020","label":"Progressive spastic paraplegia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011220","label":"Prominent forehead","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001561","label":"Polyhydramnios","frequency":"Occasional (29-5%)","criteria":null}]}}