{"orpha":543470,"name":"Optic atrophy-ataxia-peripheral neuropathy-global developmental delay syndrome","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":[],"definition":"A rare mitochondrial disease characterized by a variable clinical phenotype with the core features of optic atrophy, ataxia, and hypotonia. Additional common manifestations include global developmental delay with or without regression, neuropathy, spasticity, and microcephaly, less frequently seizures, movement disorder, hearing loss, and respiratory failure. Brain imaging may show abnormalities of the corpus callosum, basal ganglia, and midbrain, cerebral or cerebellar atrophy, or white matter abnormalities. The condition is frequently fatal at an early age.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-543470/","orphanet_url":"https://www.orpha.net/en/disease/detail/543470","names":{"fr":{"name":"Syndrome d'atrophie optique-ataxie-neuropathie périphérique-retard global de développement","definition":"Maladie mitochondriale rare caractérisée par un phénotype clinique variable dont les signes cardinaux sont l'atrophie optique, l'ataxie et l'hypotonie. Les autres signes cliniques courants sont un retard de développement global avec ou sans régression, une neuropathie, une spasticité et une microcéphalie, moins souvent des crises convulsives, des troubles du mouvement, une perte auditive et une insuffisance respiratoire. L'IRM peut révéler des malformations du corps calleux, des ganglions de la base et du mésencéphale, une atrophie cérébrale ou cérébelleuse, ou des anomalies de la substance blanche. Cette maladie est souvent létale à un âge précoce."},"de":{"name":"Optikusatrophie-Ataxie-periphere Neuropathie-globale Entwicklungsverzögerung-Syndrom","definition":"Eine seltene mitochondriale Erkrankung, die durch einen variablen klinischen Phänotyp mit den Hauptmerkmalen Optikusatrophie, Ataxie und Hypotonie gekennzeichnet ist. Weitere häufige Manifestationen sind eine globale Entwicklungsverzögerung mit oder ohne Regression, Neuropathie, Spastizität und Mikrozephalie, seltener Krampfanfälle, Bewegungsstörungen, Hörverlust und Ateminsuffizienz. Die Bildgebung des Gehirns kann Anomalien des Corpus callosum, der Basalganglien und des Mittelhirns, zerebrale oder zerebelläre Atrophie oder Anomalien der weißen Substanz zeigen. Die Erkrankung verläuft häufig in jungen Jahren tödlich."},"es":{"name":"Síndrome de atrofia óptica-ataxia-neuropatía periférica-retraso global del desarrollo","definition":"Es una enfermedad mitocondrial poco frecuente caracterizada por un fenotipo clínico variable con las características básicas de atrofia óptica, ataxia e hipotonía. Otras manifestaciones comunes incluyen retraso global del desarrollo con o sin regresión, neuropatía, espasticidad y microcefalia, y con menor frecuencia, crisis epilépticas, trastornos del movimiento, pérdida auditiva e insuficiencia respiratoria. La neuroimagen puede mostrar anomalías del cuerpo calloso, de los ganglios basales y del mesencéfalo, atrofia cerebral o cerebelosa o alteraciones de la sustancia blanca. La entidad suele ser fatal a una edad temprana."},"it":{"name":"Sindrome atrofia ottica - atassia - neuropatia periferica - ritardo dello sviluppo globale","definition":"Si tratta di una malattia mitocondriale rara, caratterizzata da un quadro clinico variabile, i cui segni clinici caratteristici sono l'atrofia ottica, l'atassia e l'ipotonia. Altri sintomi comuni sono il ritardo dello sviluppo globale con o senza regressione, la neuropatia, la spasticità e la microcefalia. Sono meno comuni le crisi epilettiche, le anomalie del movimento, la sordità e l'insufficienza respiratoria. Le neuroimmagini mostrano anomalie del corpo calloso, dei gangli basali e del mesencefalo, atrofia cerebrale o cerebellare e anomalie della sostanza bianca. Spesso la malattia è letale nell'età giovanile."},"nl":{"name":"Opticusatrofie - ataxie - perifere neuropathie - algehele ontwikkelingsachterstand-syndroom","definition":"Een zeldzame mitochondriale aandoening, gekarakteriseerd door een variabel klinisch fenotype met als kernkenmerken opticusatrofie, ataxie, en hypotonie. Bijkomende gangbare manifestaties zijn onder meer algehele ontwikkelingsachterstand met of zonder regressie, neuropathie, spasticiteit, en microcefalie, en minder frequent insulten, bewegingsstoornis, gehoorverlies, en respiratoir falen. Beeldvorming van hersenen toont mogelijk afwijkingen van corpus callosum, basale ganglia, en middenhersenen, cerebrale of cerebellaire atrofie, of afwijkingen van witte stof. De aandoening is vaak fataal op jonge leeftijd."},"pt":{"name":"Síndrome de atrofia óptica-ataxia-neuropatia periférica-atraso global do desenvolvimento"},"pl":{"name":"Zespół atrofii nerwu wzrokowego, ataksji, obwodowej neuropatii i całościowego opóźnienia rozwoju"},"cs":{"name":"Syndrom zahrnující optickou atrofii, ataxii, periferní neuropatii a celkové opoždění vývoje"},"uk":{"name":"Синдром атрофії зорового нерва-атаксії-периферичної нейропатії-глобальної затримки розвитку","definition":"A rare mitochondrial disease characterized by a variable clinical phenotype with the core features of optic atrophy, ataxia, and hypotonia. Additional common manifestations include global developmental delay with or without regression, neuropathy, spasticity, and microcephaly, less frequently seizures, movement disorder, hearing loss, and respiratory failure. Brain imaging may show abnormalities of the corpus callosum, basal ganglia, and midbrain, cerebral or cerebellar atrophy, or white matter abnormalities. The condition is frequently fatal at an early age."},"zh":{"name":"视神经萎缩-共济失调-周围神经病变-全身发育迟缓综合征"},"tr":{"name":"Optik atrofi-ataksi-periferik nöropati-yaygın gelişme geriliği sendromu"}},"xrefs":[{"source":"OMIM","code":"620887","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E88.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C58.Y","qualifier":"NTBT","icd_relation":"attributed","validated":true,"icd11_uri":"null"},{"source":"MONDO","code":"0034092","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5681321","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":309136,"name":"Mitochondrial disorder due to a defect in assembly or maturation of the respiratory chain complexes","classifications":[150,156]},{"orpha":68385,"name":"Neurometabolic disease","classifications":[156,181]},{"orpha":207018,"name":"Rare hereditary metabolic disease with peripheral neuropathy","classifications":[156,181]},{"orpha":90642,"name":"Rare syndromic genetic deafness","classifications":[147,156,200]},{"orpha":611314,"name":"Rare syndromic intellectual disability without multiple congenital anomalies/dysmorphic syndrome","classifications":[156,181]},{"orpha":441434,"name":"Syndromic hereditary optic neuropathy","classifications":[156,189]}],"children":[],"genes":[{"symbol":"FDXR","name":"ferredoxin reductase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"29040572[PMID]","hgnc":"3642","ensembl":"ENSG00000161513","omim":"103270","loci":["17q25.1"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Adolescent","Childhood","Infancy"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":17.0,"area":"Worldwide","status":"Validated","source":"29040572[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_29040572[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2020-08-19","source":"29040572[PMID]_30250212[PMID]","terms":[{"hpo":"HP:0010862","label":"Delayed fine motor development","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002194","label":"Delayed gross motor development","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000750","label":"Delayed speech and language development","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001508","label":"Failure to thrive","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000648","label":"Optic atrophy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0012087","label":"Abnormal mitochondrial shape","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002376","label":"Developmental regression","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002465","label":"Poor speech","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000505","label":"Visual impairment","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002134","label":"Abnormal basal ganglia morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001273","label":"Abnormal corpus callosum morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100022","label":"Abnormality of movement","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000062","label":"Ambiguous genitalia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008936","label":"Axial hypotonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000618","label":"Blindness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000518","label":"Cataract","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000603","label":"Central scotoma","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001272","label":"Cerebellar atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001320","label":"Cerebellar vermis hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012430","label":"Cerebral white matter hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008665","label":"Clitoral hypertrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012448","label":"Delayed myelination","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002506","label":"Diffuse cerebral atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002353","label":"EEG abnormality","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002066","label":"Gait ataxia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001276","label":"Hypertonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002079","label":"Hypoplasia of the corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007333","label":"Hypoplasia of the frontal lobes","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012794","label":"Periventricular white matter hypodensities","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0100602","label":"Preeclampsia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001622","label":"Premature birth","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012697","label":"Small basal ganglia","frequency":"Occasional (29-5%)","criteria":null}]}}