{"orpha":423479,"name":"X-linked intellectual disability-limb spasticity-retinal dystrophy-arginine vasopressin deficiency","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["X-linked intellectual disability-limb spasticity-retinal dystrophy-diabetes insipidus syndrome"],"definition":"X-linked intellectual disability-limb spasticity-retinal dystrophy-diabetes insipidus syndrome is a rare genetic neurometabolic disease characterized by severe intellectual disability, spastic quadriparesis, Leber´s congenital amaurosis and diabetes insipidus. Additional manifestations include facial dysmorphy (dolichocephalic skull, hypertelorism, deep-set eyes, hypoplastic nares, low-set ears), short stature, truncal hypotonia and axial hypertonia. Brain anomalies (e.g. thin corpus callosum with lack of isthmus and tapered splenium, hypoplasia or atrophy of the optic chiasm, prominent lateral ventricles, diminished white matter), described on magnetic resonance imaging, have been reported. High prenatal &#945;-fetoprotein and intrauterine growth restriction is observed in routine pregnancy examination.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-423479/","orphanet_url":"https://www.orpha.net/en/disease/detail/423479","names":{"fr":{"name":"Syndrome de déficience intellectuelle liée à l'X-spasticité des membres-dystrophie de la rétine-déficit en arginine vasopressine","synonyms":["Syndrome de déficience intellectuelle liée à l'X-spasticité des membres-dystrophie de la rétine-diabète insipide"],"definition":"Le syndrome de déficience intellectuelle liée à l'X-spasticité des membres-dystrophie de la rétine-diabète insipide est un trouble neurométabolique génétique rare caractérisé par un déficit intellectuel sévère, une quadriparésie spastique, une amaurose congénitale de Leber et un diabète insipide. Les manifestations additionnelles incluent une dysmorphie faciale (crâne dolichocéphalique, hypertélorisme, yeux profondément implantés, narines hypoplasiques, oreilles basses implantées), une petite taille, une hypotonie troncale et une hypertonie axiale. Des anomalies cérébrales ont été rapportées (corps calleux fin avec absence d'isthme et splénium effilé, hypoplasie ou atrophie du chiasma optique, ventricules latéraux proéminents, diminution de la substance blanche), décrites à l'imagerie par résonance magnétique. Un taux élevé d'alpha-foetoprotéine prénatale est observé à l'examen de routine lors de la grossesse, ainsi qu'un retard de croissance intra-utérin."},"de":{"name":"X-chromosomale Intelligenzminderung-Spastizität der Extremitäten-Netzhautdystrophie-Arginin-Vasopressin-Mangel-Syndrom","definition":"Eine seltene genetische neurometabolische Krankheit, die durch schwere Intelligenzminderung, spastische Quadraparese, Amaurosis congenita Leber und Diabetes insipidus gekennzeichnet ist. Weitere Manifestationen sind Gesichtsdysmorphie (dolichozephaler Schädel, Hypertelorismus, tiefliegende Augen, hypoplastische Nase, tiefliegende Ohren), Kleinwuchs, Stammhypotonie und axiale Hypertonie. In der Magnetresonanztomographie können Hirnanomalien auftreten, z. B. dünnes Corpus callosum mit fehlendem Isthmus und verjüngtem Splenium, Hypoplasie oder Atrophie des Chiasma opticum, prominente Seitenventrikel, verminderte weiße Substanz. Ein hohes pränatales &#945;-Fetoprotein und eine intrauterine Wachstumsrestriktion werden bei routinemäßigen Schwangerschaftsuntersuchungen beobachtet."},"es":{"name":"Discapacidad intelectual ligada al cromosoma X-espasticidad de las extremidades-distrofia retiniana-deficiencia de arginina vasopresina","definition":"El síndrome de discapacidad intelectual ligada al X - espasticidad de las extremidades - distrofia retiniana - diabetes insípida es una enfermedad genética neurometabólica poco frecuente caracterizada por una discapacidad intelectual grave, cuadriparesia espástica, amaurosis congénita de Leber y diabetes insípida. Las manifestaciones adicionales incluyen dismorfia facial (cráneo dolicocéfalo, hipertelorismo, ojos profundamente hundidos, fosas nasales hipoplásicas, orejas de implantación baja), baja estatura, hipotonía troncal e hipertonía axial. También se han descrito anomalías cerebrales (p.ej. cuerpo calloso delgado con ausencia de istmo y esplenio cónico, hipoplasia o atrofia del quiasma óptico, ventrículos laterales prominentes, sustancia blanca disminuida) en estudios de imagen de resonancia magnética. Asimismo, se ha observado la presencia de niveles elevados de &#945;-fetoproteína prenatal y una restricción del crecimiento intrauterino en los exámenes rutinarios durante el embarazo."},"it":{"name":"Disabilità intellettiva legata all'X-spasticità degli arti-distrofia della retina-deficit di arginina vasopressina","synonyms":["Sindrome disabilità intellettiva legata all'X-spasticità degli arti-distrofia retinica-diabete insipido"],"definition":"La sindrome da disabilità intellettiva legata all'X-spasticità degli arti-distrofia retinica-diabete insipido è una malattia neurometabolica genetica rara, caratterizzata da grave disabilità intellettiva, quadriparesi spastica, amaurosi congenita di Leber e diabete insipido. Altri segni clinici sono i dismorfismi facciali (dolicocefalia, ipertelorismo, occhi infossati, ipoplasia delle narici, orecchie a bassa attaccatura), la bassa statura, l'ipotonia del tronco e l'ipertonia assiale. La risonanza magnetica evidenzia anomalie cerebrali (assottigliamento del corpo calloso, mancanza dell'istmo, splenio affusolato, ipoplasia o atrofia del chiasma ottico, ventricoli laterali prominenti, riduzione della sostanza bianca). Gli esami di routine in gravidanza evidenziano un aumento dei valori dell'&#945;-fetoproteina e un ritardo della crescita intrauterina."},"nl":{"name":"X-gebonden intellectuele achterstand - spasticiteit van ledemaat - retinadystrofie - deficiëntie van arginine-vasopressine-syndroom","definition":"X-gebonden intellectuele achterstand - spasticiteit van de ledematen - retinale dystrofie - diabetes insipidus-syndroom is een zeldzame, genetische neurometabole aandoening die gekarakteriseerd wordt door ernstige intellectuele achterstand, quadriparese, Leber congenitale amaurose en diabetes insipidus. Bijkomende manifestaties zijn onder meer faciale dysmorfie (dolichocefale schedel, hypertelorisme, verzonken ogen, hypoplastische neusgaten, laagstaande oren), kleine gestalte, truncale hypotonie, en axiale hypertonie. Hersenanomalieën (e.g. dun corpus callosum zonder isthmus en met kegelvormig splenium, hypoplasie of atrofie van het optisch chiasma, uitgesproken laterale ventrikels, verminderde hoeveelheid witte stof), die werden beschreven bij beeldvorming met magnetische resonantie werden reeds gerapporteerd. Tijdens routineuze zwangerschapsonderzoeken worden een hoog gehalte prenataal alfafoetoproteïne en intra-uteriene groeirestrictie waargenomen."},"pt":{"name":"Perturbação do desenvolvimento intelectual ligada ao X-espasticidade dos membros-distrofia da retina-deficiência de arginina vasopressina"},"pl":{"name":"Zespół niepełnosprawności intelektualnej sprzężonej z chromosomem X, sztywności kończyn, dystrofii siatkówki i moczówki prostej","synonyms":["Niepełnosprawność intelektualna sprzężona z chromosomem X – spastyczność kończyn – dystrofia siatkówki – niedobór wazopresyny argininowej"]},"cs":{"name":"X-vázaný syndrom zahrnující mentální retardaci, spasticitu končetin, dystrofii sítnice a diabetes insipidus","synonyms":["X-linked intellectual disability-limb spasticity-retinal dystrophy-diabetes insipidus syndrome"]},"uk":{"name":"Х-зчеплена розумова відсталість-спастичність кінцівок-дистрофія сітківки- дефіцит аргінін-вазопресину","synonyms":["Х-зчеплений синдром розумової відсталості-спастичності кінцівок-дистрофії сітківки-цукрового діабету"],"definition":"X-linked intellectual disability-limb spasticity-retinal dystrophy-diabetes insipidus syndrome is a rare genetic neurometabolic disease characterized by severe intellectual disability, spastic quadraparesis, Leber´s congenital amaurosis and diabetes insipidus. Additional manifestations include facial dysmorphy (dolichocephalic skull, hypertelorism, deep-set eyes, hypoplastic nares, low-set ears), short stature, truncal hypotonia and axial hypertonia. Brain anomalies (e.g. thin corpus callosum with lack of isthmus and tapered splenium, hypoplasia or atrophy of the optic chiasm, prominent lateral ventricles, diminished white matter), described on magnetic resonance imaging, have been reported. High prenatal &#945;-fetoprotein and intrauterine growth restriction is observed in routine pregnancy examination."},"zh":{"name":"X连锁遗传智力障碍-肢体痉挛-视网膜营养不良-尿崩症综合征","definition":"X连锁智力障碍-肢体痉挛-视网膜营养不良-糖尿病尿崩症是一种罕见的遗传性神经代谢疾病，其特征是严重的智力残疾，痉挛性四肢瘫痪，莱贝尔先天性黑矇症和尿崩症。其他表现包括面部畸形（颅骨过长畸形，器官间距过远，眼睛深陷，鼻孔发育不良，耳位低），身材矮小，躯干肌张力低下和轴向性肌张力过高。已经报道的磁共振成像中描述的大脑异常有缺乏峡部和锥形压部的胼胝体，视交叉的发育不良或萎缩，侧脑室突出，白质减少）。在常规妊娠检查中可观察到产前α-甲胎蛋白过高和宫内生长受限。"},"tr":{"name":"X'e bağlı zihinsel yetersizlik-ekstremite spastisitesi-retina distrofi-diabetes insipidus sendromu"}},"xrefs":[{"source":"ICD-10","code":"Q87.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"LD90","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0018495","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4517296","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":79191,"name":"Disorder of purine metabolism","classifications":[150,156]},{"orpha":68385,"name":"Neurometabolic disease","classifications":[156,181]},{"orpha":716405,"name":"Rare disorder with progressive generalized retinal disorder as a major feature","classifications":[156,189]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]}],"children":[],"genes":[{"symbol":"PRPS1","name":"phosphoribosyl pyrophosphate synthetase 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"24961627[PMID]","hgnc":"9462","ensembl":"ENSG00000147224","omim":"311850","loci":["Xq22.3"]}],"genes_via_subtypes":[],"inheritance":["X-linked recessive"],"onset":["Antenatal","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":2.0,"area":"Worldwide","status":"Validated","source":"24961627[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_24961627[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-08-14","source":"26089585[PMID]_24961627[PMID]","terms":[{"hpo":"HP:0002187","label":"Intellectual disability, profound","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008058","label":"Aplasia/Hypoplasia of the optic nerve","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008936","label":"Axial hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002069","label":"Bilateral tonic-clonic seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000490","label":"Deeply set eye","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012448","label":"Delayed myelination","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000873","label":"Diabetes insipidus","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000268","label":"Dolichocephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004639","label":"Elevated amniotic fluid alpha-fetoprotein","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000577","label":"Exotropia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011471","label":"Gastrostomy tube feeding in infancy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006801","label":"Hyperactive deep tendon reflexes","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000316","label":"Hypertelorism","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001511","label":"Intrauterine growth retardation","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002509","label":"Limb hypertonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000369","label":"Low-set ears","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001116","label":"Macular coloboma","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000543","label":"Optic disc pallor","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012736","label":"Profound global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000556","label":"Retinal dystrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000407","label":"Sensorineural hearing impairment","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001525","label":"Severe failure to thrive","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0004322","label":"Short stature","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030211","label":"Slow pupillary light response","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001285","label":"Spastic tetraparesis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000430","label":"Underdeveloped nasal alae","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007965","label":"Undetectable visual evoked potentials","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030927","label":"1-minute APGAR score of 0","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030921","label":"5-minute APGAR score of 1","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003487","label":"Babinski sign","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010536","label":"Central sleep apnea","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002169","label":"Clonus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006579","label":"Prolonged neonatal jaundice","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011903","label":"HbH hemoglobin","frequency":"Excluded (0%)","criteria":null}]}}