{"orpha":1486,"name":"Lethal congenital contracture syndrome type 1","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":["Herva disease","LCCS1","Multiple contracture syndrome, Finnish type"],"definition":"Lethal congenital contracture syndrome type 1 is a rare, genetic arthrogryposis syndrome characterized by total fetal akinesia (detectable since the 13th week of gestation) accompanied by hydrops, micrognathia, pulmonary hypoplasia, pterygia and multiple joint contractures (usually flexion contractures in the elbows and extension in the knees), leading invariably to death before the 32nd week of gestation. Lack of anterior horn motoneurons, severe atrophy of the ventral spinal cord and severe skeletal muscle hypoplasia are characteristic neuropathological findings, with no evidence of other organ structural anomalies.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-1486/","orphanet_url":"https://www.orpha.net/en/disease/detail/1486","names":{"fr":{"name":"Syndrome des contractures congénitales létales type 1","synonyms":["LCCS1","Maladie de Herva","Syndrome des contractures multiples type finlandais"],"definition":"Un syndrome génétique rare d'arthrogrypose caractérisé par une akinésie totale foetale (détectable à partir de la 13ème semaine de grossesse), accompagnée par une anasarque, une micrognathie, une hypoplasie pulmonaire, un ptérygium et de multiples contractures articulaires (surtout des contractures de flexion au niveau des coudes et des contractures en extension au niveau des genoux). L'issue est invariablement fatale avant la 32ème semaine de grossesse. Les signes neuropathologiques caractéristiques sont le manque de motoneurones au niveau de la corne antérieure, une atrophie sévère de la moelle épinière ventrale et une hypoplasie sévère des muscles squelettiques, en l'absence d'anomalie structurelle d'autres organes."},"de":{"name":"Syndrom der kongenitalen letalen Kontrakturen Typ 1","synonyms":["Herva-Krankheit","LCCS1","Syndrom der multiplen Kontrakturen, finnischer Typ"],"definition":"Ein seltenes, genetisch bedingtes Arthrogrypose-Syndrom, das durch eine totale fetale Akinese (nachweisbar ab der 13. Schwangerschaftswoche), begleitet von Hydrops, Mikrognathie, pulmonaler Hypoplasie, Pterygium und multiplen Gelenkkontrakturen (meist Flexionskontrakturen in den Ellenbogen und Extensionskontrakturen in den Knien) gekennzeichnet ist und unweigerlich zum Tod vor der 32 Schwangerschaftswoche führt. Das Fehlen von Vorderhorn-Motoneuronen, eine schwere Atrophie des ventralen Rückenmarks und eine schwere Skelettmuskelhypoplasie sind charakteristische neuropathologische Befunde, ohne Hinweise auf andere Organstrukturanomalien."},"es":{"name":"Síndrome de contracturas congénitas letales tipo 1","synonyms":["Enfermedad de Herva","LCCS1","Síndrome de contracturas múltiples tipo finlandés"],"definition":"El síndrome de contracturas congénitas letales tipo 1 es un síndrome de artrogriposis genético y poco frecuente, caracterizado por acinesia fetal total (detectable desde la semana 13 de gestación) acompañada de hidropesía, micrognatia, hipoplasia pulmonar, pterigión y contracturas articulares múltiples (generalmente contracturas por flexión en los codos y por extensión de las rodillas), lo que lleva sistemáticamente a la muerte antes de la semana 32 de gestación. Son hallazgos neuropatológicos característicos la ausencia de motoneuronas en el asta anterior, la atrofia grave de la médula espinal ventral y la hipoplasia musculoesquelética grave, sin evidencia de anomalías estructurales en otros órganos."},"it":{"name":"Sindrome da contratture congenite letali, tipo 1","synonyms":["LCCS1","Malattia di Herva","Sindrome da contratture multiple, tipo finlandese"],"definition":"La sindrome da contratture congenite letali tipo 1 è una malattia genetica rara da artrogriposi, caratterizzata da acinesia fetale completa (che può essere individuata a partire dalla tredicesima settimana di gestazione), associata ad idrope, micrognazia, ipoplasia polmonare, pterigi e contratture articolari multiple (di solito i gomiti sono contratti in flessione e le ginocchia in estensione), che esita costantemente nella morte del feto prima della trentaduesima settimana di gestazione. I segni neuropatologici caratteristici comprendono la mancanza di motoneuroni delle corna anteriori, l'atrofia marcata del midollo spinale ventrale e la grave ipoplasia dei muscoli scheletrici. Non si evidenziano anomalie strutturali negli altri organi."},"nl":{"name":"Letale congenitale contracturen-syndroom type 1","synonyms":["LCCS1","Meervoudige contracturen-syndroom, Fins type","Ziekte van Herva"],"definition":"Letaal congenitaal contractuursyndroom type 1 is een zeldzaam, genetisch artrogryposesyndroom dat gekarakteriseerd wordt door totale foetale akinesie (detecteerbaar vanaf de 13de week van de gestatie), samen met hydrops, micrognathie, pulmonale hypoplasie, pterygium, en meervoudige gewrichtscontracturen (meestal flexiecontracturen in de ellebogen en extensie in de knieën), en dat steevast resulteert in overlijden voor de 32ste week van de gestatie. Typische neuropathologische bevindingen zijn een gebrek aan motorneuronen in de voorhoorn, ernstige atrofie van het ventrale ruggenmerg en ernstige hypoplasie van skeletspieren, terwijl er geen bewijs is van structurele anomalieën aan andere organen."},"pt":{"name":"Síndrome de contraturas congénitas letais tipo 1","synonyms":["Doença de Herva","Síndrome de artrogripose congénita letal","Síndrome de artrogripose múltipla tipo filandês"]},"pl":{"name":"Letalny zespół wrodzonych przykurczów stawowych typu 1","synonyms":["Choroba Herva","LCCS1","Zespół mnogich przykurczów, typu fińskiego"]},"cs":{"name":"Vrozený letální syndrom kontraktur, typ 1","synonyms":["Nemoc Hervaové","LCCS1","Syndrom mnohočetných kontraktur, finský typ"]},"uk":{"name":"Летальний синдром вродженої контрактури, тип 1","synonyms":["Хвороба Герва","LCCS1","Синдром множинних контрактур, фінський тип"],"definition":"Lethal congenital contracture syndrome type 1 is a rare, genetic arthrogryposis syndrome characterized by total fetal akinesia (detectable since the 13th week of gestation) accompanied by hydrops, micrognathia, pulmonary hypoplasia, pterygia and multiple joint contractures (usually flexion contractures in the elbows and extension in the knees), leading invariably to death before the 32nd week of gestation. Lack of anterior horn motoneurons, severe atrophy of the ventral spinal cord and severe skeletal muscle hypoplasia are characteristic neuropathological findings, with no evidence of other organ structural anomalies."},"zh":{"name":"致死性先天性关节挛缩综合征1型","synonyms":["多发性挛缩综合征，芬兰型"]},"tr":{"name":"Letal Doğumsal kontraktür sendromu tip 1","synonyms":["LCCS1","Herva hastalığı","çoklu kontraktür sendromu, Fin tipi"]}},"xrefs":[{"source":"OMIM","code":"253310","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q68.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"LD26.4Y","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"1662577564"},{"source":"MONDO","code":"0009670","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C537194","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C1854664","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"3227","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":330206,"name":"Genetic multiple congenital anomalies/dysmorphic syndrome without intellectual disability","classifications":[156]},{"orpha":294965,"name":"Lethal congenital contracture syndrome","classifications":[147,156]},{"orpha":102285,"name":"Multiple congenital anomalies/dysmorphic syndrome without intellectual disability","classifications":[147]},{"orpha":108993,"name":"Non-syndromic respiratory or mediastinal malformation","classifications":[156]},{"orpha":108995,"name":"Syndromic respiratory or mediastinal malformation","classifications":[147,186]},{"orpha":182108,"name":"Thoracic malformation","classifications":[184]}],"children":[],"genes":[{"symbol":"GLE1","name":"GLE1 RNA export mediator","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"18204449[PMID]","hgnc":"4315","ensembl":"ENSG00000119392","omim":"603371","loci":["9q34.11"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Antenatal","Neonatal"],"prevalence":[{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Finland","status":"Validated","source":"32670090[PMID]_ORPHANET"},{"type":"Prevalence at birth","qualification":"Value and class","class":"1-9 / 100 000","value":3.96,"area":"Finland","status":"Validated","source":"16892327[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2016-06-01","source":null,"terms":[{"hpo":"HP:0003272","label":"Abnormality of the hip bone","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000316","label":"Hypertelorism","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0000347","label":"Micrognathia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002089","label":"Pulmonary hypoplasia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0004322","label":"Short stature","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003202","label":"Skeletal muscle atrophy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003103","label":"Abnormal cortical bone morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000772","label":"Abnormal rib morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009811","label":"Abnormality of the elbow","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009775","label":"Amniotic constriction ring","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001376","label":"Limitation of joint mobility","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001561","label":"Polyhydramnios","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000358","label":"Posteriorly rotated ears","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002757","label":"Recurrent fractures","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000470","label":"Short neck","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003100","label":"Slender long bone","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000465","label":"Webbed neck","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003312","label":"Abnormal form of the vertebral bodies","frequency":"Occasional (29-5%)","criteria":null}]}}