{"orpha":521426,"name":"PLAA-associated neurodevelopmental disorder","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":["PLAAND"],"definition":"A rare genetic neurological disorder characterized by infantile onset of progressive leukoencephalopathy, microcephaly, severe global developmental delay, and spasticity resulting in quadriparesis and posture deformation. Additional features include an abnormally exaggerated startle reflex, seizures, dystonia, and hypomimia or amimia, as well as progressive chest deformities and contractures of large and hyperextensibility of small joints, among others. Thin corpus callosum is a prominent feature in brain imaging, in addition to white matter abnormalities consistent with leukoencephalopathy.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-521426/","orphanet_url":"https://www.orpha.net/en/disease/detail/521426","names":{"fr":{"name":"Trouble neurologique du développement associé à PLAA","synonyms":["PLAAND"],"definition":"Maladie neurologique génétique rare caractérisée par l'apparition infantile d'une leucoencéphalopathie progressive, d'une microcéphalie, d'un retard de développement global sévère et d'une spasticité entraînant une quadriparésie et une déformation de la posture. Les signes cliniques incluent un réflexe de sursaut anormalement exagéré, des crises convulsives, une dystonie et une hypomimie ou une amimie, ainsi que des malformations thoraciques progressives et des contractures des grandes articulations et des hyperextensibilités des petites articulations. Le signe dominant observable à l'IRM est un corps calleux mince, en plus des anomalies de la substance blanche compatibles avec une leucoencéphalopathie."},"de":{"name":"PLAA-assoziierte neurologische Entwicklungsstörung","synonyms":["PLAAND"],"definition":"Eine seltene genetisch bedingte neurologische Störung, die sich durch eine im Säuglingsalter einsetzende progressive Leukoenzephalopathie, Mikrozephalie, eine schwere globale Entwicklungsverzögerung und Spastizität auszeichnet, die zu Quadriparese und Haltungsfehlbildungen führt. Weitere Merkmale sind ein abnorm übertriebener Schreckreflex, Krampfanfälle, Dystonie und Hypomimie oder Amimie sowie fortschreitende Fehlbildungen des Brustkorbs und Kontrakturen der großen und Überstreckbarkeit der kleinen Gelenke. Ein dünnes Corpus callosum ist ein auffälliges Merkmal in der Bildgebung des Gehirns, zusätzlich zu den Anomalien der weißen Substanz, die mit einer Leukoenzephalopathie einhergehen."},"es":{"name":"Trastorno del neurodesarrollo asociado a PLAA","synonyms":["PLAAND"],"definition":"Es un trastorno neurológico de origen genético poco frecuente caracterizado por el inicio en la lactancia de leucoencefalopatía progresiva, microcefalia, grave retraso global del desarrollo y espasticidad que deriva en tetraparesia y deformación de la postura. Otros hallazgos adicionales incluyen una respuesta de sobresalto anormalmente exagerada, crisis epilépticas, distonía e hipo- o amimia, así como malformaciones torácicas progresivas y contracturas de las grandes articulaciones e hiperextensibilidad de las pequeñas articulaciones, entre otras. El adelgazamiento del cuerpo calloso es un hallazgo destacado en la neuroimagen, junto con alteraciones de la sustancia blanca compatibles con leucoencefalopatía."},"it":{"name":"Malattia dello sviluppo neurologico associata a PLAA","synonyms":["PLAAND"],"definition":"Si tratta di una malattia neurologica genetica rara, caratterizzata da leucoencefalopatia progressiva ad esordio infantile, microcefalia, grave ritardo dello sviluppo globale e spasticità, che esita nella tetraparesi e nella deformazione della postura. Altri segni clinici sono i sussulti anomali, le crisi epilettiche, la distonia, l'ipomimia o l'amimia, le deformità progressive del torace, le contratture delle grandi articolazioni e l'iperlassità delle piccole articolazioni. Le neuroimmagini mostrano un assottigliamento del corpo calloso e anomalie della sostanza bianca coerenti con la leucoencefalopatia."},"nl":{"name":"PLAA-geassocieerde neurologische ontwikkelingsstoornis","synonyms":["PLAAND"],"definition":"Een zeldzame genetische neurologische aandoening, gekarakteriseerd door infantiele aanvang van progressieve leuko-encefalopathie, microcefalie, ernstige algehele ontwikkelingsachterstand, en spasticiteit die leidt tot quadriparese en misvormde lichaamshouding. Bijkomende kenmerken zijn onder meer een abnormaal overdreven schrikreflex, insulten, dystonie, en hypomimie of amimie, alsook progressieve misvormingen van borstkas, contracturen van grote gewrichten en hypermobiliteit van kleine gewrichten. Dun corpus callosum is een belangrijk kenmerk bij beeldvorming van hersenen, naast afwijkingen van witte stof die consistent zijn met leuko-encefalopathie."},"pt":{"name":"Perturbação do neurodesenvolvimento PLAA-associada"},"pl":{"name":"Zaburzenie neurorozwojowe związane z PLAA","synonyms":["PLAAND"]},"cs":{"name":"Neurovývojová porucha asociovaná s PLAA","synonyms":["PLAAND"]},"uk":{"name":"PLAA-асоційоване порушення нейророзвитку","synonyms":["PLAAND"],"definition":"A rare genetic neurological disorder characterized by infantile onset of progressive leukoencephalopathy, microcephaly, severe global developmental delay, and spasticity resulting in quadriparesis and posture deformation. Additional features include an abnormally exaggerated startle reflex, seizures, dystonia, and hypomimia or amimia, as well as progressive chest deformities and contractures of large and hyperextensibility of small joints, among others. Thin corpus callosum is a prominent feature in brain imaging, in addition to white matter abnormalities consistent with leukoencephalopathy."},"zh":{"name":"PLAA基因相关的神经发育障碍","synonyms":["PLAAND"],"definition":"一种罕见的遗传性神经系统疾病，其特点是婴儿期开始出现进行性脑白质病、小头畸形、严重的全面发育迟缓和痉挛，导致四肢轻瘫和姿态变形。其他特征还包括异常夸张的惊吓反射、癫痫发作、肌张力障碍和表情缺乏或无表情，以及进行性胸部畸形和大关节挛缩、小关节伸展过度等。胼胝体薄是脑影像学的一个突出特点，此外，白质异常与脑白质病相一致。"},"tr":{"name":"PLAA-ilişkili nörogelişimsel bozukluk","synonyms":["PLAAND"]}},"xrefs":[{"source":"OMIM","code":"617527","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q87.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0060502","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4479631","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":441434,"name":"Syndromic hereditary optic neuropathy","classifications":[156,189]}],"children":[],"genes":[{"symbol":"PLAA","name":"phospholipase A2 activating protein","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"28007986[PMID]_28413018[PMID]","hgnc":"9043","ensembl":"ENSG00000137055","omim":"603873","loci":["9p21.2"]}],"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":"28007986[PMID]_28413018[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_28007986[PMID]_28413018[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-03-20","source":"28413018[PMID]_28007986[PMID]","terms":[{"hpo":"HP:0002536","label":"Abnormal cortical gyration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001999","label":"Abnormal facial shape","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002071","label":"Abnormality of extrapyramidal motor function","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002104","label":"Apnea","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001283","label":"Bulbar palsy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008278","label":"Cerebellar cortical atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012762","label":"Cerebral white matter atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005781","label":"Contractures of the large joints","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012448","label":"Delayed myelination","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000750","label":"Delayed speech and language development","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012098","label":"Edema of the dorsum of feet","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007514","label":"Edema of the dorsum of hands","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002267","label":"Exaggerated startle response","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001508","label":"Failure to thrive","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011968","label":"Feeding difficulties","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000218","label":"High palate","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001007","label":"Hirsutism","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001187","label":"Hyperextensibility of the finger joints","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002521","label":"Hypsarrhythmia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0031162","label":"Impaired oropharyngeal swallow response","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001249","label":"Intellectual disability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002808","label":"Kyphosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002352","label":"Leukoencephalopathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002509","label":"Limb hypertonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100807","label":"Long fingers","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000343","label":"Long philtrum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000347","label":"Micrognathia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000648","label":"Optic atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000768","label":"Pectus carinatum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001830","label":"Postaxial foot polydactyly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001162","label":"Postaxial hand polydactyly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000358","label":"Posteriorly rotated ears","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002478","label":"Progressive spastic quadriplegia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002093","label":"Respiratory insufficiency","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002063","label":"Rigidity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001838","label":"Rocker bottom foot","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003196","label":"Short nose","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000954","label":"Single transverse palmar crease","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000319","label":"Smooth philtrum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010804","label":"Tented upper lip vermilion","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002483","label":"Bulbar signs","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000975","label":"Hyperhidrosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000407","label":"Sensorineural hearing impairment","frequency":"Occasional (29-5%)","criteria":null}]}}