{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T04:35:35Z","timestamp":1785818135766,"version":"3.56.0"},"reference-count":25,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T00:00:00Z","timestamp":1762819200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Smith\u2010Kingsmore syndrome (SKS) is a rare autosomal dominant condition characterized by neurodevelopmental differences, macrocephaly\/megalencephaly, describable facial features, sleep\u2013wake abnormalities, hyperphagia, and overgrowth. SKS is caused by pathogenic gain\u2010of\u2010function variants in MTOR which lead to hyperactivation of the mTOR pathway. In this review, we discuss the history, epidemiology, molecular basis, clinical features, and management considerations for Smith\u2010Kingsmore syndrome. In addition, we provide insight on early developmental milestones through a report on 14 individuals with a confirmed diagnosis of SKS. Among these individuals, 8\/12 (67%) achieved crawling at an average age of 23\u2009months, 9\/14 (64%) achieved walking with an average age of 32\u2009months, 5\/9 (56%) achieved a pincer grasp at an average age of 23\u2009months, 8\/12 (67%) achieved the ability to use a device or utensil with an average age of 3.4\u2009years, 10\/13 (77%) achieved babbling at an average age of 20\u2009months, 8\/14 (57%) achieved their first word at an average age of 34\u2009months, and 4\/14 (29%) achieved the use of short phrases at an average age of 4.6\u2009years. This review highlights advances in characterizing the natural history of SKS since it was first described 12\u2009years ago and the need for additional research to inform genotype\u2013phenotype correlations and targeted therapies to support individuals with SKS.<\/jats:p>","DOI":"10.1002\/ajmg.a.64307","type":"journal-article","created":{"date-parts":[[2025,11,11]],"date-time":"2025-11-11T11:04:26Z","timestamp":1762859066000},"page":"800-806","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Syndrome of the Month: An Update on Smith\u2010Kingsmore Syndrome: Characterization of Developmental Milestones and a Review of the Literature"],"prefix":"10.1002","volume":"200","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7488-2662","authenticated-orcid":false,"given":"Carolyn R.","family":"Raski","sequence":"first","affiliation":[{"name":"Division of Genetics &amp; Rare Diseases Ann &amp; Robert H. Lurie Children's Hospital of Chicago  Chicago Illinois USA"},{"name":"Department of Pediatrics, Feinberg School of Medicine Northwestern University  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3348-3531","authenticated-orcid":false,"given":"Carlos E.","family":"Prada","sequence":"additional","affiliation":[{"name":"Division of Genetics &amp; Rare Diseases Ann &amp; Robert H. Lurie Children's Hospital of Chicago  Chicago Illinois USA"},{"name":"Department of Pediatrics, Feinberg School of Medicine Northwestern University  Chicago Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,11,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37070"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1009651"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmg.2025.105012"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13931"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-021-01161-6"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.13135"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61007"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1183"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1159\/000515672"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.5734\/JGM.2019.16.1.27"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm.3824"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.xhgg.2024.100333"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaneurol.2016.0363"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000118"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37999"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-015-0240-8"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62350"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-021-01256-0"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41431-019-0418-1"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2017.03.035"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3757"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.4137\/JGE.S12583"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics11071269"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11083"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1177\/0883073818813238"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.64307","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ajmg.a.64307","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.64307","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T09:01:01Z","timestamp":1773046861000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.64307"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,11]]},"references-count":25,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2026,4]]}},"alternative-id":["10.1002\/ajmg.a.64307"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.64307","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,11]]},"assertion":[{"value":"2025-08-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-11-11","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}