{"orpha":2680,"name":"Hypomyelination neuropathy-arthrogryposis syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":[],"definition":"Hypomyelination neuropathy-arthrogryposis syndrome is a rare, genetic, limb malformation syndrome characterized by multiple congenital distal joint contractures (incl. talipes equinovarus and both proximal and distal interphalangeal joint contractures of the hands) and very severe motor paralysis at birth (i.e. lack of swallowing, autonomous respiratory function and deep tendon reflexes), leading to death within first 3 months of life. Fetal hypo- or akinesia, late-onset polyhydramnios and dramatically reduced, or absent, motor nerve conduction velocities (<10 m/s) are frequently associated. Nerve ultrastructural morphology shows severe abnormalities of the nodes of Ranvier and myelinated axons.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-2680/","orphanet_url":"https://www.orpha.net/en/disease/detail/2680","names":{"fr":{"name":"Syndrome de neuropathie hypomyélinisante-arthrogrypose","definition":"Syndrome d'origine génétique rare avec anomalie des membres caractérisé par de multiples contractures congénitales des articulations distales (pied bot en varus équin et contractures des articulations interphalangiennes proximales et distales des mains) et une infirmité motrice très sévère à la naissance (absence de déglutition, de fonction respiratoire autonome et de réflexes tendineux profonds), conduisant au décès dans les 3 premiers mois de la vie. L'hypokinésie ou l'akinésie foetale, le polyhydramnios tardif et des vitesses de conduction nerveuse motrice considérablement réduites, voire absentes (<10 m/s) sont fréquemment associés. La morphologie ultrastructurale du nerf montre de graves anomalies des noeuds de Ranvier et des axones myélinisés."},"de":{"name":"Hypomyelinisierung-Neuropathie-Arthrogrypose-Syndrom","synonyms":["Boylan-Dew-Syndrom"],"definition":"Ein seltenes, genetisch bedingtes Gliedmaßenfehlbildungssyndrom, das durch multiple angeborene distale Gelenkkontrakturen (inkl. Klumpfüße und proximale und distale Interphalangealgelenkkontrakturen der Hände) und sehr schwere motorische Lähmungen bei der Geburt (d.h. Fehlen von Schlucken, autonomer Atemfunktion und tiefen Sehnenreflexen) gekennzeichnet ist und zum Tod innerhalb der ersten 3 Lebensmonate führt. Fetale Hypo- oder Akinesie, spät einsetzender Polyhydramnion und dramatisch reduzierte oder fehlende motorische Nervenleitgeschwindigkeiten (<10 m/s) sind häufig assoziiert. Die ultrastrukturelle Morphologie der Nerven zeigt schwere Anomalien der Ranvier-Knoten und der myelinisierten Axone."},"es":{"name":"Síndrome de neuropatía por hipomielinización-artrogriposis","definition":"Es un síndrome malformativo de las extremidades, genético y poco frecuente, caracterizado por múltiples contracturas congénitas de las articulaciones distales (incluyendo talipes equinovarus y contracturas de las articulaciones interfalángicas proximales y distales de las manos) y parálisis motora muy grave al nacimiento (es decir, incapacidad para: tragar, función respiratoria autónoma y reflejos osteotendinosos), que conducen a fallecimiento en los primeros 3 meses de vida. Con frecuencia, se asocian hipo- o acinesia fetal, polihidramnios de inicio tardío y velocidades de conducción nerviosa motora drásticamente reducidas (<10 m/s) o ausentes. La morfología ultraestructural del nervio muestra graves anomalías en los nódulos de Ranvier y axones mielinizados."},"it":{"name":"Sindrome da neuropatia ipomielinizzante e artrogriposi","synonyms":["Sindrome di Boylan-Dew"],"definition":"La sindrome da neuropatia ipomielinizzante e artrogriposi è una malformazione genetica rara degli arti, caratterizzata da contratture multiple congenite delle articolazioni distali (piedi equino-vari e contratture articolari interfalangee prossimali e distali nelle mani) e paralisi motoria molto grave alla nascita (assenza della deglutizione, funzione respiratoria autonoma e riflessi tendinei profondi), che esita nel decesso nei primi tre mesi di vita. Spesso si associa a ipocinesia o acinesia fetale, polidramnios tardivo, e velocità di conduzione dei nervi motori rallentate o assenti (<10 m/s). La morfologia ultrastrutturale dei nervi evidenzia gravi anomalie dei nodi di Ranvier e degli assoni mielinizzati."},"nl":{"name":"Hypomyeliniserende neuropathie - artrogrypose-syndroom","definition":"Hypomyeliniserende neuropathie - artrogrypose-syndroom is een zeldzaam, genetisch malformatiesyndroom van de ledematen dat gekarakteriseerd wordt door meervoudige congenitale distale gewrichtscontracturen (inclusief talipes equinovarus en zowel proximale als distale interfalangeale gewrichtscontracturen van de handen) en zeer ernstige motorische paralyse bij de geboorte (i.e. gebrek aan slikvermogen, autonome ademhaling en diepe peesreflexen), en dat leidt tot overlijden binnen de eerste 3 levensmaanden. Foetale hypo- of akinesie, laat aanvangende polyhydramnion en dramatisch verminderde, or afwezige, motorische zenuwgeleidingssnelheden (<10 m/s) zijn frequent geassocieerd. Analyse van de ultrastructurele morfologie van zenuwen toont ernstige afwijkingen van de knopen van Ranvier en gemyeliniseerde axonen."},"pt":{"name":"Síndrome de neuropatia por hipomielinização-artrogripose"},"pl":{"name":"Neuropatia hipomielinizacyjna - artrogrypoza","synonyms":["Zespół Boylana i Dew"],"definition":"*Neuropatia hipomielinizacyjna - artrogrypoza jest rzadkim, genetycznie uwarunkowanym zespołem wad rozwojowych kończyn, w którym występują wrodzone przykurcze wielu stawów dystalnych (w tym stopy końsko-szpotawe oraz przykurcze zarówno proksymalnych, jak i dystalnych stawów międzypaliczkowych rąk) i ciężki niedowład ruchowy przy urodzeniu (tj. brak połykania, autonomicznych funkcji oddechowych i głębokich odruchów ścięgnistych), co prowadzi do śmierci w ciągu pierwszych 3 miesięcy życia. Często obserwuje się hipo- lub akinezję (bezruch) płodu, wielowodzie o późnym początku oraz radykalne zwolnienie lub brak przewodzenia w nerwach ruchowych (inf 10 m/s). W ultrastrukturalnym obrazie nerwów obserwuje się poważne nieprawidłowości w przewężeniach Ranviera i włóknach zmielinizowanych."},"cs":{"name":"Syndrom zahrnující neuropatii s hypomyelinizací a artrogrypózu","synonyms":["Boylanův-Dewův syndrom"]},"uk":{"name":"Синдром гіпомієлінізаційної нейропатії-артрогрипозу","definition":"Hypomyelination neuropathy-arthrogryposis syndrome is a rare, genetic, limb malformation syndrome characterized by multiple congenital distal joint contractures (incl. talipes equinovarus and both proximal and distal interphalangeal joint contractures of the hands) and very severe motor paralysis at birth (i.e. lack of swallowing, autonomous respiratory function and deep tendon reflexes), leading to death within first 3 months of life. Fetal hypo- or akinesia, late-onset polyhydramnios and dramatically reduced, or absent, motor nerve conduction velocities (<10 m/s) are frequently associated. Nerve ultrastructural morphology shows severe abnormalities of the nodes of Ranvier and myelinated axons."},"zh":{"name":"脱髓鞘神经病变-关节挛缩综合征"},"tr":{"name":"Hipomiyelinasyon nöropati-artrogripozis sendromu"}},"xrefs":[{"source":"OMIM","code":"616286","qualifier":"BTNT","icd_relation":null,"validated":false},{"source":"OMIM","code":"616287","qualifier":"BTNT","icd_relation":null,"validated":false},{"source":"OMIM","code":"617468","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"618186","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q68.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0017049","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4707882","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":1037,"name":"Arthrogryposis multiplex congenita","classifications":[147,156]}],"children":[],"genes":[{"symbol":"LGI4","name":"leucine rich repeat LGI family member 4","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) (loss of function) in","status":"Assessed","source":"28318499[PMID]","hgnc":"18712","ensembl":"ENSG00000153902","omim":"608303","loci":["19q13.12"]},{"symbol":"ADCY6","name":"adenylate cyclase 6","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"24319099[PMID]","hgnc":"237","ensembl":"ENSG00000174233","omim":"600294","loci":["12q13.12"]},{"symbol":"CNTNAP1","name":"contactin associated protein 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"24319099[PMID]","hgnc":"8011","ensembl":"ENSG00000108797","omim":"602346","loci":["17q21.2"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Antenatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":9.0,"area":"Worldwide","status":"Validated","source":"24319099[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_24319099[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2016-06-01","source":null,"terms":[{"hpo":"HP:0003457","label":"EMG abnormality","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001376","label":"Limitation of joint mobility","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001315","label":"Reduced tendon reflexes","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002098","label":"Respiratory distress","frequency":"Very frequent (99-80%)","criteria":null}]}}