{"orpha":481152,"name":"PYCR2-related microcephaly-progressive leukoencephalopathy","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":[],"definition":"PYCR2-related microcephaly-progressive leukoencephalopathy is a rare, genetic, syndromic intellectual disability disorder characterized by progressive postnatal microcephaly, cerebral hypomyelination and severe psychomotor developmental delayed with absent speech, as well as axial hypotonia, appendicular hypertonia with hyperextensibility of the wrists and ankles, hyperreflexia, severe muscle wasting and failure to thrive. Associated craniofacial dysmorphism includes triangular facies with bitemporal narrowing, down- or upslanting palpebral fissures, malar hypoplasia, large malformed ears with overfolded helices, upturned bulbous nose, long smooth philtrum and thin vermilion borders.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-481152/","orphanet_url":"https://www.orpha.net/en/disease/detail/481152","names":{"fr":{"name":"Microcéphalie avec leucoencéphalopathie progressive associée à PYCR2","definition":"Déficience intellectuelle syndromique rare d'origine génétique, caractérisée par une microcéphalie post-natale progressive, une hypomyélinisation cérébrale et un retard de développement psychomoteur sévère avec absence de parole, ainsi qu'une hypotonie axiale, une hypertonie appendiculaire avec hyperextensibilité des poignets et des chevilles, une hyperréflexie, une atrophie musculaire et un retard de croissance sévères. La dysmorphie craniofaciale associée comprend un faciès triangulaire avec un rétrécissement bitemporal, des fentes palpébrales inclinées vers le bas ou vers le haut, une hypoplasie malaire, de grandes oreilles malformées avec des hélices ourlées, un nez bulbeux retroussé, un long philtrum lisse et un vermillon fin."},"de":{"name":"PYCR2-abhängige Mikrozephalie-progressive Leukoenzephalopathie"},"es":{"name":"Microcefalia asociada a PYCR2-leucoencefalopatía progresiva","definition":"Es un trastorno de discapacidad intelectual sindrómico, genético y poco frecuente, caracterizado por microcefalia postnatal progresiva, hipomielinización cerebral y retraso grave del desarrollo psicomotor con ausencia del habla, así como hipotonía axial, hipertonía apendicular con hiperextensibilidad de las muñecas y los tobillos, hiperreflexia, pérdida muscular grave y fallo de medro. La dismorfia craneofacial asociada incluye facies triangular con estrechamiento bitemporal, fisuras palpebrales inclinadas hacia arriba o hacia abajo, hipoplasia malar, orejas grandes y malformadas con hélix plegados, nariz bulbosa y respingona, surco nasolabial largo y liso, y bordes bermellón delgados."},"it":{"name":"Microcefalia con leucoencefalopatia progressiva correlata a PYCR2","definition":"La microcefalia con leucoencefalopatia progressiva correlata a PYCR2 è una malattia genetica rara da disabilità intellettiva sindromica, caratterizzata da microcefalia postnatale progressiva, ipomielinizzazione cerebrale, grave ritardo dello sviluppo psicomotorio, assenza del linguaggio, ipotonia assiale, ipertonia appendicolare con iperestensibilità dei polsi e delle caviglie, iperreflessia, atrofia muscolare grave e ritardo della crescita. I dismorfismi craniofacciali caratteristici comprendono il viso triangolare con restringimento bitemporale, le rime palpebrali oblique verso il basso o l'alto, ipoplasia malare, le orecchie grandi e malformate con eccessiva plicatura dell'elice, il naso globoso con la punta rivolta verso l'alto, il filtro lungo e liscio e l'assottigliamento della porzione mucosa delle labbra."},"nl":{"name":"PYCR2-gerelateerde microcefalie - progressieve leuko-encefalopathie","definition":"PYCR2-gerelateerde microcefalie - progressieve leuko-encefalopathie is een zeldzame, genetische, syndromale intellectuele invaliditeit, gekarakteriseerd door progressieve postnatale microcefalie, cerebrale hypomyelinisatie en ernstige psychomotorische ontwikkelingsachterstand met afwezigheid van spraak, alsook axiale hypotonie, appendiculaire hypertonie met hyperextensibiliteit van polsen en enkels, hyperreflexie, ernstige spieratrofie, en groeiachterstand. Geassocieerde craniofaciale dysmorfie omvat driehoekig gezicht met bitemporale vernauwing, schuin naar beneden of opwaarts hellende ooglidspleten, malaire hypoplasie, grote misvormde oren met overmatig gevouwen helices, bolle wipneus, lang en glad filtrum en dunne vermiljoengrenzen."},"pt":{"name":"Microcefalia-leucoencefalopatia progressiva PYCR2-relacionada"},"pl":{"name":"Małogłowie - postępująca leukoencefalopatia zależne od PYCR2","definition":"*Małogłowie - postępująca leukoencefalopatia zależne od PYCR2 jest rzadkim, genetycznie uwarunkowanym zespołem z niepełnosprawnością intelektualną, który charakteryzuje się postępującym po urodzeniu małogłowiem, hipomielinizacją mózgu i znacznie opóźnionym rozwojem psychoruchowym z brakiem mowy, a także hipotonią osiową, wzmożonym napięciem mięśni kończyn z nadmierną ruchomością nadgarstków i stawów skokowych, wygórowanymi odruchami ścięgnistymi, znacznymi zanikami mięśni i zaburzeniami prawidłowego rozwoju. Towarzysząca dysmorfia twarzowo-czaszkowa obejmuje trójkątną twarz z dwuskroniowym zwężeniem, skośnie ku górze lub ku dołowi ustawione szpary powiekowe, hipoplazję kości jarzmowych, duże, zniekształcone uszy z nadmiernie zagiętym obrąbkiem, zadarty bulwiasty nos, długą wygładzoną rynienkę wargową i cienkie brzegi czerwieni wargowej."},"cs":{"name":"PYCR2-vázaná mikrocefalie s progresivní leukoencefalopatií"},"uk":{"name":"PYCR2-асоційована мікроцефалія-прогресуюча лейкоенцефалопатія","definition":"PYCR2-related microcephaly-progressive leukoencephalopathy is a rare, genetic, syndromic intellectual disability disorder characterized by progressive postnatal microcephaly, cerebral hypomyelination and severe psychomotor developmental delayed with absent speech, as well as axial hypotonia, appendicular hypertonia with hyperextensibility of the wrists and ankles, hyperreflexia, severe muscle wasting and failure to thrive. Associated craniofacial dysmorphism includes triangular facies with bitemporal narrowing, down- or upslanting palpebral fissures, malar hypoplasia, large malformed ears with overfolded helices, upturned bulbous nose, long smooth philtrum and thin vermilion borders."},"zh":{"name":"PYCR2相关小头畸形-进行性脑白质发育不良","definition":"PYCR2基因相关的小头畸形-进行性脑白质病是一种罕见的遗传性、综合征性智力障碍疾病，其特征为出生后进行性小头畸形、大脑低髓鞘化和严重的精神运动发育迟缓，伴有言语缺失，以及轴性肌张力低下、附属肌张力亢进，伴有腕部和踝部伸展过度、反射亢进、严重肌萎缩和发育停滞。相关的颅面畸形包括三角形面容伴双颞变窄，下或上斜睑裂，颊部发育不良，畸形大耳伴耳轮过度折叠，球鼻上翘，人中长而平，薄唇缘点。"},"tr":{"name":"PYCR2 -ilişkili mikrosefali ilerleyici lökoensefalopati"}},"xrefs":[{"source":"OMIM","code":"616420","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q87.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0018825","qualifier":"E","icd_relation":null,"validated":true},{"source":"MONDO","code":"14632","qualifier":"E","icd_relation":null,"validated":true},{"source":"MONDO","code":"18825","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4225332","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":611327,"name":"Genetic multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[156]},{"orpha":102283,"name":"Multiple congenital anomalies/dysmorphic syndrome-intellectual disability","classifications":[147,181]},{"orpha":269528,"name":"Syndrome with microcephaly as a major feature","classifications":[147,156,181]}],"children":[],"genes":[{"symbol":"PYCR2","name":"pyrroline-5-carboxylate reductase 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"25865492[PMID]_27130255[PMID]","hgnc":"30262","ensembl":"ENSG00000143811","omim":"616406","loci":["1q42.12"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":18.0,"area":"Worldwide","status":"Validated","source":"25865492[PMID]_27130255[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_25865492[PMID]_27130255[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2020-01-08","source":"27860360[PMID]_27130255[PMID]_25865492[PMID]","terms":[{"hpo":"HP:0001344","label":"Absent speech","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001508","label":"Failure to thrive","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002540","label":"Inability to walk","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000253","label":"Progressive microcephaly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0011344","label":"Severe global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001999","label":"Abnormal facial shape","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000414","label":"Bulbous nose","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003429","label":"CNS hypomyelination","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002376","label":"Developmental regression","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030890","label":"Hyperintensity of cerebral white matter on MRI","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000327","label":"Hypoplasia of the maxilla","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000369","label":"Low-set ears","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000411","label":"Protruding ear","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007258","label":"Severe demyelination of the white matter","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003202","label":"Skeletal muscle atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002013","label":"Vomiting","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000924","label":"Abnormality of the skeletal system","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001274","label":"Agenesis of corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000718","label":"Aggressive behavior","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000463","label":"Anteverted nares","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001166","label":"Arachnodactyly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002069","label":"Bilateral tonic-clonic seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011229","label":"Broad eyebrow","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0010055","label":"Broad hallux","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011304","label":"Broad thumb","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100704","label":"Cerebral visual impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000494","label":"Downslanted palpebral fissures","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000565","label":"Esotropia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001371","label":"Flexion contracture","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011166","label":"Focal myoclonic seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001288","label":"Gait disturbance","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002283","label":"Global brain atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000365","label":"Hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000218","label":"High palate","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002827","label":"Hip dislocation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005072","label":"Hyperextensibility at wrists","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001347","label":"Hyperreflexia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000316","label":"Hypertelorism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002365","label":"Hypoplasia of the brainstem","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006460","label":"Increased laxity of ankles","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000737","label":"Irritability","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001382","label":"Joint hypermobility","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002509","label":"Limb hypertonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000343","label":"Long philtrum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000400","label":"Macrotia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000341","label":"Narrow forehead","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000396","label":"Overfolded helix","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000768","label":"Pectus carinatum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002465","label":"Poor speech","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000319","label":"Smooth philtrum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000233","label":"Thin vermilion border","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005659","label":"Thoracic kyphoscoliosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000325","label":"Triangular face","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000582","label":"Upslanted palpebral fissure","frequency":"Occasional (29-5%)","criteria":null}]}}