{"orpha":2363,"name":"Lacrimoauriculodentodigital syndrome","type":"Malformation syndrome","group":"Disorder","status":"active","flags":[],"synonyms":["LADD syndrome","LARD syndrome","Lacrimoauriculoradiodental syndrome","Levy-Hollister syndrome"],"definition":"A rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by hypoplasia, aplasia or atresia of the lacrimal system, anomalies of the ears with sensorineural or mixed hearing loss, hypoplasia, aplasia or atresia of the salivary glands, dental anomalies, and digital malformations. Patients present obstruction of the nasal lacrimal ducts that can lead to epiphora, and chronic conjunctivitis due to alacrimia. Aplasia or hypoplasia of the salivary glands lead to dry mouth and early onset of severe dental caries. Dental features include late tooth eruption, small and peg-shaped lateral maxillary incisors and mild enamel dysplasia. The digital features are variable and include fifth finger clinodactyly, duplication of the distal phalanx of the thumb, triphalangeal thumb, and/or syndactyly. Unilateral radial aplasia and radial-ulnar synostosis have also been reported in association.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-2363/","orphanet_url":"https://www.orpha.net/en/disease/detail/2363","names":{"fr":{"name":"Syndrome lacrymo-auriculo-dento-digital","synonyms":["Syndrome LADD","Syndrome LARD","Syndrome de Levy-Hollister","Syndrome lacrymo-auriculo-radio-dental"],"definition":"Anomalies congénitales multiples/syndrome dysmorphique caractérisé par une hypoplasie, une aplasie ou une atrésie de l'appareil lacrymal, des anomalies d'oreilles associées à une surdité neurosensorielle ou mixte, une hypoplasie, une aplasie ou une atrésie des glandes salivaires, des anomalies dentaires et des malformations digitales. Les patients présentent une obstruction du canal lacrymo-nasal pouvant entraîner un épiphora et une conjonctivite chronique due à l'alacrimie. L'aplasie ou l'hypoplasie des glandes salivaires entraîne une sécheresse buccale et l'apparition précoce de caries dentaires sévères. Les anomalies dentaires comprennent un retard d'éruption dentaire, des incisives latérales maxillaires petites et de forme conique et une légère dysplasie de l'émail. Les malformations digitales sont inconstantes et comprennent une clinodactylie du 5<sup>e</sup> doigt, une duplication de la phalange distale du pouce, une triphalangie du pouce et/ou une syndactylie. Une association avec une aplasie radiale unilatérale et une synostose radio-ulnaire a également été rapportée."},"de":{"name":"Lakrimo-aurikulo-dento-digitales Syndrom","synonyms":["LADD-Syndrom","LARD-Syndrom","Lakrimo-aurikulo-radio-dentales Syndrom","Levy-Hollister-Syndrom"],"definition":"Ein genetisch bedingtes multiples Fehlbildungssyndrom, das durch Hypoplasie, Aplasie oder Atresie des Tränenapparats, Anomalien der Ohren mit sensorineuralem oder gemischtem Hörverlust, Hypoplasie, Aplasie oder Atresie der Speicheldrüsen, Zahnanomalien und Fehlbildungen der Finger/Zehen gekennzeichnet ist. Die Patienten weisen eine Obstruktion der Tränenkanäle in der Nase auf, die zu Epiphora und chronischer Bindehautentzündung aufgrund von Alakrimie führen kann. Aplasie oder Hypoplasie der Speicheldrüsen führen zu Mundtrockenheit und frühzeitigem Auftreten von schwerer Zahnkaries. Zu den zahnmedizinischen Merkmalen gehören ein verspäteter Zahndurchbruch, kleine und zapfenförmige seitliche obere Schneidezähne und eine leichte Dysplasie des Zahnschmelzes. Die digitalen Merkmale sind variabel und umfassen Klinodaktylie des fünften Fingers, Duplikation der distalen Phalanx des Daumens, Daumen mit drei Fingern und/oder Syndaktylie. Eine einseitige Radialaplasie und eine Radial-Ulnar-Synostose wurden ebenfalls in Verbindung mit dieser Erkrankung berichtet."},"es":{"name":"Síndrome lácrimo-aurículo-dento-digital","synonyms":["Síndrome LADD","Síndrome LARD","Síndrome de Levy Hollister","Síndrome lácrimo-aurículo-radio-dental"],"definition":"Es un síndrome dismórfico/ con anomalías congénitas múltiples, de origen genético y poco frecuente, caracterizado por hipoplasia, aplasia o atresia del sistema lagrimal, anomalías del oído con pérdida auditiva neurosensorial o mixta, hipoplasia, aplasia o atresia de las glándulas salivales, anomalías dentales y malformaciones de los dedos. Los pacientes presentan obstrucción de los conductos lagrimales nasales que puede provocar epífora, y conjuntivitis crónica por alacrimia. La aplasia o hipoplasia de las glándulas salivales provoca sequedad en la boca y la aparición temprana de caries dentales graves. La afectación dental incluye una erupción dental tardía, incisivos laterales maxilares pequeños y en forma de clavija y displasia leve del esmalte. Las características digitales son variables e incluyen clinodactilia del quinto dedo de la mano, duplicación de la falange distal del pulgar, pulgar trifalángico y/o sindactilia. También se ha descrito la asociación de aplasia radial unilateral y sinostosis radio-cubital."},"it":{"name":"Sindrome lacrimo-auriculo-dento-digitale","synonyms":["Sindrome di Levy-Hollister","Sindrome lacrimo-auriculo-radio-dentale","Sindrome LADD","Sindrome LARD"],"definition":"La sindrome lacrimo-auriculo-dento-digitale (LADD) è una malattia da anomalie congenite multiple, caratterizzata da ipoplasia, aplasia o atresia dell'apparato lacrimale; anomalie dell'orecchio e sordità; ipoplasia, aplasia o atresia delle ghiandole salivari; anomalie dei denti e malformazioni delle dita."},"nl":{"name":"Lacrimo-auriculo-dento-digitaal syndroom","synonyms":["LADD-syndroom","LARD-syndroom","Lacrimo-auriculo-radio-dentaal syndroom","Levy-Hollistersyndroom"],"definition":"Een zeldzaam, genetisch syndroom met multipele congenitale anomalieën/dysmorfie, gekarakteriseerd door hypoplasie, aplasie of atresie van het traansysteem, anomalieën van de oren met sensorineuraal of gemengd gehoorverlies, hypoplasie, aplasie of atresie van speekselklieren, dentale anomalieën, en digitale malformaties. Patiënten vertonen obstructie van nasale traankanalen, wat kan leiden tot epifora (tranende ogen), en chronische conjunctivitis als gevolg van alacrimie. Aplasie of hypoplasie van speekselklieren leidt tot droge mond en vroege aanvang van ernstige cariës. Dentale kenmerken zijn onder meer late tanderuptie, kleine en kegelvormige laterale maxillaire snijtanden, en milde dysplasie van tandglazuur. De digitale kenmerken zijn variabel, en met onder meer clinodactylie van vijfde vinger, duplicatie van distale falanx van de duim, trifalangeale duim, en/of syndactylie. Associatie van unilaterale aplasie van radius en radiale-ulnaire synostose werd ook reeds gerapporteerd."},"pt":{"name":"Síndrome lacrimo-auriculo-dento-digital","synonyms":["Síndrome LADD","Síndrome LARD","Síndrome Levy-Hollister"]},"pl":{"name":"Zespół łzowo-uszno-zębowo-palcowy","synonyms":["Zespół LADD","Zespół LARD","Zespół Levy'ego i Hollistera","Zespół łzowo-uszno-promieniowo-zębowy"]},"cs":{"name":"Lakrimoaurikulodentodigitální syndrom","synonyms":["LADD syndrom","LARD syndrom","Lakrimoaurikuloradiodentální syndrom","Levyho-Hollisterův syndrom","Levy-Hollisterův syndrom"]},"uk":{"name":"Лакримоаурикулодентодигітальний синдром","synonyms":["Лакримоаурикулорадіодентальний синдром","Синдром LADD","LARD-синдром","Синдром Леві-Голлістера"],"definition":"A rare, genetic, multiple congenital anomalies/dysmorphic syndrome characterized by hypoplasia, aplasia or atresia of the lacrimal system, anomalies of the ears with sensorineural or mixed hearing loss, hypoplasia, aplasia or atresia of the salivary glands, dental anomalies, and digital malformations. Patients present obstruction of the nasal lacrimal ducts that can lead to epiphora, and chronic conjunctivitis due to alacrimia. Aplasia or hypoplasia of the salivary glands lead to dry mouth and early onset of severe dental caries. Dental features include late tooth eruption, small and peg-shaped lateral maxillary incisors and mild enamel dysplasia. The digital features are variable and include fifth finger clinodactyly, duplication of the distal phalanx of the thumb, triphalangeal thumb, and/or syndactyly. Unilateral radial aplasia and radial-ulnar synostosis have also been reported in association."},"zh":{"name":"泪管-耳-齿-指综合征","synonyms":["泪管-耳-齿-指综合征"]},"tr":{"name":"Lacrimoauriculodentodigital sendromu","synonyms":["LADD sendromu","LARD sendromu","Levy-Hollister sendromu","Lakrimoaurikuloradiyodental sendromu"]}},"xrefs":[{"source":"OMIM","code":"149730","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"620192","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"620193","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"Q87.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"LD27.0Y","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"475956869"},{"source":"MONDO","code":"0007872","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C538132","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0265269","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"6848","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10085252","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":93890,"name":"Rare developmental defect during embryogenesis"},"parents":[{"orpha":98609,"name":"EEC syndrome and related disorders","classifications":[147,156,187,189]},{"orpha":183580,"name":"Genetic malformation syndrome with odontal and/or periodontal component","classifications":[156]},{"orpha":330206,"name":"Genetic multiple congenital anomalies/dysmorphic syndrome without intellectual disability","classifications":[156]},{"orpha":435606,"name":"Genetic nose and cavum anomaly","classifications":[156]},{"orpha":139042,"name":"Malformation syndrome with odontal and/or periodontal component","classifications":[147,197]},{"orpha":102285,"name":"Multiple congenital anomalies/dysmorphic syndrome without intellectual disability","classifications":[147]},{"orpha":156246,"name":"Nose and cavum anomaly","classifications":[147,200]},{"orpha":294959,"name":"Syndrome with limb duplication, polydactyly, syndactyly, and/or hyperphalangy","classifications":[147,156,199]}],"children":[],"genes":[{"symbol":"FGF10","name":"fibroblast growth factor 10","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"16630169[PMID]","hgnc":"3666","ensembl":"ENSG00000070193","omim":"602115","loci":["5p12"]},{"symbol":"FGFR2","name":"fibroblast growth factor receptor 2","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"16501574[PMID]","hgnc":"3689","ensembl":"ENSG00000066468","omim":"176943","loci":["10q26.13"]},{"symbol":"FGFR3","name":"fibroblast growth factor receptor 3","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"16501574[PMID]","hgnc":"3690","ensembl":"ENSG00000068078","omim":"134934","loci":["4p16.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal dominant"],"onset":["Antenatal","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":100.0,"area":"Worldwide","status":"Validated","source":"23010692[PMID]_Pr MANOUVRIER-HANU Sylvie[EXPERT]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_23010692[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2021-03-25","source":"32715658[PMID]_28483234[PMID]_28400699[PMID]_28043400[PMID]","terms":[{"hpo":"HP:0000164","label":"Abnormality of the dentition","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0011297","label":"Abnormal digit morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011481","label":"Abnormal lacrimal duct morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011482","label":"Abnormal lacrimal gland morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000377","label":"Abnormal pinna morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0010286","label":"Abnormal salivary gland morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000682","label":"Abnormality of dental enamel","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000478","label":"Abnormality of the eye","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000670","label":"Carious teeth","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009926","label":"Epiphora","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001097","label":"Keratoconjunctivitis sicca","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000217","label":"Xerostomia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001999","label":"Abnormal facial shape","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001172","label":"Abnormal thumb morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001092","label":"Absent lacrimal punctum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009777","label":"Absent thumb","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030084","label":"Clinodactyly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000405","label":"Conductive hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0011496","label":"Corneal neovascularization","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012804","label":"Corneal ulceration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000378","label":"Cupped ear","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012155","label":"Decreased corneal sensation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009942","label":"Duplication of thumb phalanx","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006297","label":"Enamel hypoplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0006101","label":"Finger syndactyly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000668","label":"Hypodontia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007892","label":"Hypoplasia of the lacrimal punctum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002984","label":"Hypoplasia of the radius","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001096","label":"Keratoconjunctivitis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007925","label":"Lacrimal duct aplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007656","label":"Lacrimal gland aplasia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0032107","label":"Limbal stem cell deficiency","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000369","label":"Low-set ears","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000691","label":"Microdontia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000410","label":"Mixed hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000508","label":"Ptosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000495","label":"Recurrent corneal erosions","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000407","label":"Sensorineural hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0009778","label":"Short thumb","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001159","label":"Syndactyly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001770","label":"Toe syndactyly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000458","label":"Anosmia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001369","label":"Arthritis","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000813","label":"Bicornuate uterus","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000193","label":"Bifid uvula","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000453","label":"Choanal atresia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000028","label":"Cryptorchidism","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002015","label":"Dysphagia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000577","label":"Exotropia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000126","label":"Hydronephrosis","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0005349","label":"Hypoplasia of the epiglottis","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0011487","label":"Increased corneal thickness","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000347","label":"Micrognathia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0008551","label":"Microtia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002164","label":"Nail dysplasia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0012108","label":"Open angle glaucoma","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000202","label":"Orofacial cleft","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001643","label":"Patent ductus arteriosus","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000089","label":"Renal hypoplasia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002650","label":"Scoliosis","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000076","label":"Vesicoureteral reflux","frequency":"Very rare (<4-1%)","criteria":null}]}}