{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T22:56:37Z","timestamp":1779231397043,"version":"3.51.4"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2016,1,6]],"date-time":"2016-01-06T00:00:00Z","timestamp":1452038400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:sec><jats:label\/><jats:p>Sotos syndrome is a childhood overgrowth syndrome characterized clinically by a distinctive facial gestalt, advanced bone age, childhood overgrowth, and non\u2010progressive developmental delay; and genetically by haploinsufficiency of the Nuclear receptor binding SET Domain 1 (<jats:italic>NSD1<\/jats:italic>) gene. Generalized lymphedema has not previously been associated with Sotos syndrome. Generalized lymphedema has been associated with mutations in several genes including FLT4. This gene is involved in the regulation of VEGFR3, a key governor of lymphatic\u2010endothelial cell development and function. We report on a 28\u2010year\u2010old Caucasian female with a de novo <jats:italic>NSD1<\/jats:italic> intragenic mutation, c.5841_5848dup: p.Leu1950Serfs*22, who presented with characteristic clinical features of Sotos syndrome. Unusually this case includes atypical features of intrauterine growth retardation and post\u2010pubertal onset of primary lymphedema. To our knowledge, no link between Sotos syndrome and generalized lymphedema has previously been described in the literature. We propose a mechanism by which disruptions in <jats:italic>NSD1<\/jats:italic> gene may lead to generalized lymphedema. Aberrations of the mitogen\u2010activated protein kinase (MAPK)\/extracellular signal\u2010regulated kinase (ERK)\u2010signaling pathway has been identified in both Sotos syndrome and lymphedema. This finding extends the known phenotype of Sotos syndrome through the inclusion of lymphedema. This case also indicates that presence of low birth weight does not exclude the possibility of Sotos syndrome. \u00a9 2016 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37535","type":"journal-article","created":{"date-parts":[[2016,1,7]],"date-time":"2016-01-07T12:24:11Z","timestamp":1452169451000},"page":"1064-1069","source":"Crossref","is-referenced-by-count":8,"title":["Sotos syndrome: An unusual presentation with intrauterine growth restriction, generalized lymphedema, and intention tremor"],"prefix":"10.1002","volume":"170","author":[{"given":"Jessie","family":"McClelland","sequence":"first","affiliation":[{"name":"University of Newcastle Callaghan New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bronwyn","family":"Burgess","sequence":"additional","affiliation":[{"name":"Hunter Genetics Waratah New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patricia","family":"Crock","sequence":"additional","affiliation":[{"name":"University of Newcastle Callaghan New South Wales Australia"},{"name":"Pediatric Endocrinology John Hunter Children's Hospital New Lambton Height New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Himanshu","family":"Goel","sequence":"additional","affiliation":[{"name":"University of Newcastle Callaghan New South Wales Australia"},{"name":"Hunter Genetics Waratah New South Wales Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2016,1,6]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.30492"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.35814"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.31.1.20"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/345647"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1086\/302248"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2009.12.009"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-1119(01)00750-8"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng863"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2008.11.013"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/20.17.4762"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000354097"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.4.285"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1911"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/cdg288"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/35020506"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.40.6.436"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9343(00)00727-0"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM196407162710301"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1086\/432082"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/00019605-200410000-00001"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201686"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201050"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0049229"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.GIM.0000178503.15559.d3"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.sap.0000257149.42922.7e"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.37535","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.37535","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.37535","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,9]],"date-time":"2023-09-09T19:28:13Z","timestamp":1694287693000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.37535"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,1,6]]},"references-count":25,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,4]]}},"alternative-id":["10.1002\/ajmg.a.37535"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.37535","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,1,6]]}}}