{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T12:30:20Z","timestamp":1790857820426,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T00:00:00Z","timestamp":1691625600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Pulmonology"],"published-print":{"date-parts":[[2023,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Fibroblast growth factor 10 (FGF10) is a signaling molecule with a well\u2010established role for lung branching morphogenesis. Rare heterozygous, deleterious variants in the <jats:italic>FGF10<\/jats:italic> gene are known causes of the lacrimo\u2010auriculo\u2010dento\u2010digital (LADD) syndrome and aplasia of lacrimal and salivary glands.\u00a0Previous studies indicate that pathogenic variants in <jats:italic>FGF10<\/jats:italic> can cause childhood Interstitial Lung Disease (chILD) due to severe diffuse developmental disorders of the lung, but detailed reports on clinical presentation and follow\u2010up of affected children are lacking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We describe four children with postnatal onset of chILD and heterozygous variants in <jats:italic>FGF10<\/jats:italic>, each detected by exome or whole genome sequencing.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All children presented with postnatal respiratory failure. Two children died within the first 2 days of life, one patient died at age of 12 years due to right heart failure related to severe pulmonary hypertension (PH) and one patient is alive at age of 6\u00a0years, but still symptomatic. Histopathological analysis of lung biopsies from the two children with early postpartum demise revealed diffuse developmental disorder representing acinar dysplasia and interstitial fibrosis. Sequential biopsies of the child with survival until the age of 12 years revealed alveolar simplification and progressive interstitial fibrosis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>Our report extends the phenotype of <jats:italic>FGF10<\/jats:italic>\u2010related disorders to early onset chILD with progressive interstitial lung fibrosis and PH. Therefore, <jats:italic>FGF10\u2010<\/jats:italic>related disorder should be considered even without previously described syndromic stigmata in children with postnatal respiratory distress, not only when leading to death in the neonatal period but also in case of persistent respiratory complaints and PH.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ppul.26627","type":"journal-article","created":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T12:31:31Z","timestamp":1691670691000},"page":"3095-3105","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Variants in <i>FGF10<\/i> cause early onset of severe childhood interstitial lung disease: A detailed description of four affected children"],"prefix":"10.1002","volume":"58","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2680-3541","authenticated-orcid":false,"given":"Katharina","family":"Sch\u00fctz","sequence":"first","affiliation":[{"name":"Clinic for Pediatric Pneumology, Allergology and Neonatology Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, School of Medicine &amp; University Hospital Bonn University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolaus","family":"Schwerk","sequence":"additional","affiliation":[{"name":"Clinic for Pediatric Pneumology, Allergology and Neonatology Hannover Medical School Hannover Germany"},{"name":"German Center for Lung Research (DZL) Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane Miriam","family":"Renz","sequence":"additional","affiliation":[{"name":"Department of Pediatric Radiology, Hannover Medical School Institute of Diagnostic and Interventional Radiology Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benedicte","family":"Gerard","sequence":"additional","affiliation":[{"name":"Laboratoires de Diagnostic G\u00e9n\u00e9tique, Unit\u00e9 de g\u00e9n\u00e9tique mol\u00e9culaire Nouvel H\u00f4pital Civil Strasbourg Cedex France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elise","family":"Schaefer","sequence":"additional","affiliation":[{"name":"Laboratoires de Diagnostic G\u00e9n\u00e9tique, Unit\u00e9 de g\u00e9n\u00e9tique mol\u00e9culaire Nouvel H\u00f4pital Civil Strasbourg Cedex France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Cristina","family":"Antal","sequence":"additional","affiliation":[{"name":"UF6349 f\u0153topathologie, D\u00e9partement de Pathologie H\u00f4pitaux Universitaires Strasbourg France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia","family":"Peters","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, School of Medicine &amp; University Hospital Bonn University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0113-912X","authenticated-orcid":false,"given":"Matthias","family":"Griese","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pneumology, German Center for Lung Research (DZL), Dr von Hauner Children's Hospital Ludwig\u2010Maximilians\u2010University  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina K.","family":"Rapp","sequence":"additional","affiliation":[{"name":"Department of Pediatric Pneumology, German Center for Lung Research (DZL), Dr von Hauner Children's Hospital Ludwig\u2010Maximilians\u2010University  Munich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hartmut","family":"Engels","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, School of Medicine &amp; University Hospital Bonn University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsten","family":"Cremer","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics, School of Medicine &amp; University Hospital Bonn University of Bonn Bonn Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke Katharina","family":"Bergmann","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunnar","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Auber","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5002-409X","authenticated-orcid":false,"given":"Jan C.","family":"Kamp","sequence":"additional","affiliation":[{"name":"German Center for Lung Research (DZL) Munich Germany"},{"name":"Department of Respiratory Medicine Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Laenger","sequence":"additional","affiliation":[{"name":"Hannover Medical School Institute of Pathology Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3680-7450","authenticated-orcid":false,"given":"Sandra","family":"von Hardenberg","sequence":"additional","affiliation":[{"name":"Department of Human Genetics Hannover Medical School Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,8,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.7717\/peerj.14003"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/538379"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cytogfr.2015.10.001"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3721"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/dvdy.24234"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1757"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2006.00597.x"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/mgg3.1412"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1242\/dev.124.23.4867"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.aay4353"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.2147\/COPD.S297777"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2011-100166"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-021-00902-0"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2018.12.010"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.22844"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40348-016-0045-7"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1183\/16000617.0251-2021"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2018.00545"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/5096"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-020-00222-7"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1164\/rccm.201903-0495TR"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-021-00902-0"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2022.109398"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.12.20.3156"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.5188"},{"issue":"23","key":"e_1_2_10_28_1","first-page":"4139","article-title":"Evidence for the involvement of fibroblast growth factor 10 in lipofibroblast formation during embryonic lung development","volume":"142","author":"Al Alam D","year":"2015","journal-title":"Development"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01504-2019"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01965-2018"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2012-101152"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/thorax-2022-219434"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1513\/AnnalsATS.202202-142OC"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep43469"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2020.620667"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1165\/rcmb.2020-0476TR"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1183\/13993003.01512-2022"}],"container-title":["Pediatric Pulmonology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ppul.26627","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,27]],"date-time":"2025-02-27T00:50:24Z","timestamp":1740617424000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ppul.26627"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,10]]},"references-count":36,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2023,11]]}},"alternative-id":["10.1002\/ppul.26627"],"URL":"https:\/\/doi.org\/10.1002\/ppul.26627","archive":["Portico"],"relation":{},"ISSN":["8755-6863","1099-0496"],"issn-type":[{"value":"8755-6863","type":"print"},{"value":"1099-0496","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,10]]},"assertion":[{"value":"2023-05-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-24","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-08-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}