{"orpha":300284,"name":"Connective tissue disorder due to lysyl hydroxylase-3 deficiency","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["Bone fragility-contractures-arterial rupture-deafness syndrome","Bone fragility-contractures-arterial rupture-hearing loss syndrome","Connective tissue disorder due to LH3 deficiency"],"definition":"Connective tissue disorder due to lysyl hydroxylase-3 deficiency is a rare, genetic disease, caused by lack of lysyl hydrohylase 3 (LH3) activity, characterized by multiple tissue and organ involvement, including skeletal abnormalities (club foot, progressive scoliosis, osteopenia, pathologic fractures), ocular involvement (flat retinae, myopia, cataracts) and hair, nail and skin anomalies (coarse, abnormally distributed hair, skin blistering, reduced palmar creases, hypoplastic nails). Patients also present intrauterine growth retardation, facial dysmorphism (flat facial profile, low-set ears, shallow orbits, short and upturned nose, downturned corners of mouth) and joint flexion contractures. Growth and developmental delay, bilateral sensorineural deafness, friable diaphragm and later-onset spontaneous vascular ruptures are additional reported features.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-300284/","orphanet_url":"https://www.orpha.net/en/disease/detail/300284","names":{"fr":{"name":"Maladie du tissu conjonctif par déficit en lysyl hydroxylase-3","synonyms":["Maladie du tissu conjonctif par déficit en LH3","Syndrome de fragilité osseuse-contractures-rupture artérielle-surdité"],"definition":"Une maladie génétique rare, causée par un déficit de l'activité de la lysyl hydroxylase-3 (LH3). Elle se caractérise par de multiples atteintes tissulaires et d'organe, incluant des anomalies squelettiques (pieds bots, scoliose progressive, ostéopénie, fractures pathologiques), une atteinte oculaire (rétines plates, myopie, cataractes), ainsi que des anomalies cutanées, capillaires et unguéales (cheveux d'aspect grossier, distribués de manière anormale, formation de cloques cutanées, diminution du nombre de sillons palmaires, ongles hypoplasiques). Les patients présentent également un retard de croissance intra-utérin, une dysmorphie faciale (visage plat, oreilles basses implantées, orbites peu profondes, nez court et orienté vers le haut, coins de la bouche orientés vers le bas), et des contractures articulaires de flexion. Les signes additionnels sont un retard de croissance et de développement, une surdité bilatérale neurosensorielle, un diaphragme friable et des ruptures vasculaires spontanées survenant tardivement."},"de":{"name":"Bindegewebskrankheit durch Lysyl-Hydroxylase 3-Mangel","synonyms":["Bindegewebskrankheit durch LH3-Mangel","Knochenfragilität-Kontrakturen-Arterienruptur-Schwerhörigkeit-Syndrom"],"definition":"Eine seltene, genetisch bedingte Erkrankung, die durch einen Mangel an Lysyl-Hydroxylase 3 (LH3)-Aktivität verursacht wird und durch eine Vielzahl von Gewebe- und Organbeteiligungen gekennzeichnet ist. Zu den Kennzeichen der Krankheit zählen Skelettanomalien (Klumpfuß, progressive Skoliose, Osteopenie, pathologische Frakturen), Augenbeteiligung (flache Netzhäute, Myopie, Katarakte) sowie Haar-, Nagel- und Hautanomalien (grobes, abnormal verteiltes Haar, Hautblasenbildung, reduzierte Palmarfalten, hypoplastische Nägel). Die Patienten zeigen außerdem eine intrauterine Wachstumsretardierung, Gesichtsdysmorphien (flaches Gesichtsprofil, tief angesetzte Ohren, flache Augenhöhlen, kurze und nach oben gerichtete Nase, nach unten gerichtete Mundwinkel) und Gelenkbeugekontrakturen. Wachstums- und Entwicklungsverzögerung, beidseitige sensorineurale Taubheit, brüchiges Zwerchfell und später auftretende spontane Gefäßrupturen sind weitere assoziierte Merkmale."},"es":{"name":"Enfermedad del tejido conectivo por deficiencia de lisil hidroxilasa-3","synonyms":["Enfermedad del tejido conectivo por deficiencia de LH3","Síndrome de fragilidad ósea-contracturas-ruptura arterial-hipoacusia","Síndrome de fragilidad ósea-contracturas-ruptura arterial-sordera"],"definition":"La enfermedad del tejido conectivo por deficiencia de lisil hidroxilasa-3 es una enfermedad genética poco frecuente, causada por la falta de actividad de la lisil hidrolasa 3 (LH3), caracterizada por la afectación de múltiples tejidos y órganos, incluidas anomalías esqueléticas (pie zambo, escoliosis progresiva, osteopenia, fracturas patológicas), afectación ocular (retina plana, miopía, cataratas) y anomalías del cabello, las uñas y la piel (pelo grueso y de distribución anómala, formación de ampollas en la piel, disminución de los pliegues palmares, uñas hipoplásicas). Los afectados también presentan retraso del crecimiento intrauterino, dismorfia facial (perfil facial plano, orejas de baja implantación, órbitas poco profundas, nariz corta y hacia arriba, comisuras de la boca inclinadas hacia abajo) y contracturas articulares en flexión. El retraso del desarrollo y del crecimiento, la sordera neurosensorial bilateral, el diafragma friable y las roturas vasculares espontáneas de inicio tardío son características adicionales notificadas."},"it":{"name":"Malattia del tessuto connettivo da deficit di lisil idrossilasi-3","synonyms":["Malattia del tessuto connettivo da deficit di LH3","Sindrome fragilità ossea-contratture-rottura arteriosa-sordità"],"definition":"La malattia del tessuto connettivo da deficit di lisil idrossilasi-3 è una malattia genetica rara, causata da un difetto di lisil idrossilasi-3 (LH3). La malattia interessa diversi tessuti e organi ed è caratterizzata da anomalie scheletriche (piede equino, scoliosi progressiva, osteopenia, fratture patologiche), oculari (retina piana, miopia, cataratta), della cute, dei capelli e delle unghie (capelli grossolani ad anomala distribuzione, vesciche cutanee, ridotta plicatura sul palmo delle mani, unghie ipoplasiche). I pazienti presentano anche ritardo della crescita prenatale, dismorfismi facciali (profilo piatto del viso, orecchie a basso impianto, orbite poco profonde, naso corto con punta rivolta verso l'alto, angoli della bocca rivolti verso il basso) e contratture articolari in flessione. Altri possibili segni clinici sono il ritardo della crescita e dello sviluppo, la sordità neurosensoriale bilaterale, il diaframma friabile e le rotture vascolari spontanee ad esordio più tardivo."},"nl":{"name":"Aandoening van bindweefsel door lysylhydroxylase 3-deficiëntie","synonyms":["Aandoening van bindweefsel door LH3-deficiëntie","Botfragiliteit - contracturen - ruptuur van arterie - doofheid-syndroom","Botfragiliteit - contracturen - ruptuur van arterie - gehoorverlies-syndroom"],"definition":"Bindweefselstoornis door lysylhydroxylase 3-deficiëntie is zeldzame, genetische aandoening die veroorzaakt wordt door een gebrek aan lysylhydroxylase 3 (LH3)-activiteit, en die gekarakteriseerd wordt door betrokkenheid van meerdere weefsels en organen, waaronder afwijkingen van het skelet (klompvoet, progressieve scoliose, osteopenie, pathologische fracturen), betrokkenheid van het oog (plat netvlies, myopie, cataracten) en haar-, nagel- en huidanomalieën (ruw, abnormaal verdeeld haar, blaarvorming op de huid, verminderde handpalmplooien, hypoplastische nagels). Patiënten vertonen ook intra-uteriene groeiretardatie, faciale dysmorfie (plat gelaatsprofiel, laagstaande oren, ondiepe oogkassen, korte en opwaartse neus, neerwaartse mondhoeken) en flexiecontracturen van gewrichten. Bijkomend gerapporteerde kenmerken zijn groei- en ontwikkelingsachterstand, bilaterale sensorineurale doofheid, een broos diafragma, en later aanvangende spontane vasculaire scheuringen."},"pt":{"name":"Doença do tecido conjuntivo por deficiência de lisil 3-hidroxilase","synonyms":["Conectivopatia devido a deficiência LH3","Síndrome de fragilidade óssea-contraturas-ruptura arterial-perda auditiva","Síndrome de fragilidade óssea-contraturas-ruptura arterial-surdez"]},"pl":{"name":"Choroba tkanki łącznej z powodu niedoboru hydroksylazy-3 lizylowej","synonyms":["Choroba tkanki łącznej z powodu niedoboru LH3","Zespół kruchość kości-przykurcze-pęknięcie tętnicy-głuchota"]},"cs":{"name":"Poruchy pojivové tkáně způsobené nedostatkem lysyl-3-hydroxylázy","synonyms":["Syndrom kostní fragilita, kontraktury, arteriální ruptura a hluchota","Porucha pojivové tkáně způsobená nedostatkem LH3"]},"uk":{"name":"Порушення сполучної тканини, зумовлене дефіцитом лізилгідроксилази-3","synonyms":["Синдром ламкості кісток - контрактур - розривів артерій - глухоти","Синдром ламкості кісток - контрактур - розривів артерій - втрати слуху","Порушення сполучної тканини через дефіцит LH3"],"definition":"Connective tissue disorder due to lysyl hydroxylase-3 deficiency is a rare, genetic disease, caused by lack of lysyl hydrohylase 3 (LH3) activity, characterized by multiple tissue and organ involvement, including skeletal abnormalities (club foot, progressive scoliosis, osteopenia, pathologic fractures), ocular involvement (flat retinae, myopia, cataracts) and hair, nail and skin anomalies (coarse, abnormally distributed hair, skin blistering, reduced palmar creases, hypoplastic nails). Patients also present intrauterine growth retardation, facial dysmorphism (flat facial profile, low-set ears, shallow orbits, short and upturned nose, downturned corners of mouth) and joint flexion contractures. Growth and developmental delay, bilateral sensorineural deafness, friable diaphragm and later-onset spontaneous vascular ruptures are additional reported features."},"zh":{"name":"赖氨酰羟化酶-3缺陷所致结缔组织紊乱","synonyms":["脆骨-关节挛缩-动脉破裂-听力损失综合征"],"definition":"赖氨酸羟化酶-3缺乏所致结缔组织病是一种罕见的遗传性疾病，由赖氨酸羟化酶3（LH3）活性缺乏引起，其特征是多个组织和器官受累，包括骨骼异常（曲棍球棒样足、进行性脊柱侧弯、骨质减少、病理性骨折）、眼部受累（视网膜平、近视、白内障）和头发、指甲和皮肤异常（毛发粗糙、分布异常、皮肤起疱、掌纹减少、指甲发育不良）。患者还表现为宫内发育迟缓、面部畸形（面部轮廓扁平、低位耳、浅眼眶、鼻子短而上翘、嘴角下弯）和关节屈曲挛缩。生长发育迟缓、双侧感音神经性耳聋、脆性膈肌和迟发性自发性血管破裂也有报道。"},"tr":{"name":"Lizil hidroksilaz-3 eksikliğine bağlı bağ dokusu bozukluğu","synonyms":["LH3 eksikliğine bağlı bağ dokusu bozukluğu","Kemik kırılganlığı-kontraktürler-arteriyel yırtılma-sağırlık sendromu","Kemik kırılganlığı-kontraktürler-arteriyel yırtılma-işitme kaybı sendromu"]}},"xrefs":[{"source":"OMIM","code":"612394","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"M35.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"4A4Y","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0012892","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4706393","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98023,"name":"Rare systemic or rheumatologic disease"},"parents":[{"orpha":139030,"name":"Rare developmental defect with connective tissue involvement","classifications":[147,156]},{"orpha":619249,"name":"Rare hereditary connective tissue disease","classifications":[156]},{"orpha":90642,"name":"Rare syndromic genetic deafness","classifications":[147,156,200]},{"orpha":182222,"name":"Rare systemic disease","classifications":[196]}],"children":[],"genes":[{"symbol":"PLOD3","name":"procollagen-lysine,2-oxoglutarate 5-dioxygenase 3","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"18834968[PMID]","hgnc":"9083","ensembl":"ENSG00000106397","omim":"603066","loci":["7q22.1"]}],"genes_via_subtypes":[],"inheritance":["Not applicable"],"onset":["Antenatal","Neonatal"],"prevalence":[{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_18834968[PMID]"},{"type":"Cases/families","qualification":"Case(s)","class":null,"value":2.0,"area":"Worldwide","status":"Validated","source":"18834968[PMID]"}],"phenotypes":null}