{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T02:51:57Z","timestamp":1791168717897,"version":"4.1.0"},"reference-count":12,"publisher":"The Endocrine Society","issue":"11","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":10,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Luscan\u2013Lumish syndrome is a rare autosomal-dominant disorder caused by pathogenic SET domain-containing protein 2 (SETD2) variants, classically associated with postnatal overgrowth, obesity, developmental delay, seizures, and Chiari I malformation; endocrine manifestations remain poorly characterized. We report a 47-year-old woman with a novel SETD2 frameshift variant (c.4451_4454del, p.Lys1486Argfs*28) presenting with severe obesity (body mass index 62.9\u2005kg\/m2), hypogonadotropic hypogonadism, hyperprolactinemia, and neurodevelopmental manifestations. She underwent rapid weight gain of 60 pounds during adolescence without reported dietary or activity changes, accompanied by hirsutism and secondary amenorrhea. Laboratory evaluation revealed low gonadotropins (luteinizing hormone 0.3\u2005IU\/L; reference 1.9-12.5\u2005IU\/L, follicular; follicle-stimulating hormone 0.5\u2005IU\/L; reference 2.5-10.2\u2005IU\/L, follicular), low estradiol (26.4-48\u2005pg\/mL [96.9-176.2\u2005pmol\/L]; reference 30-400\u2005pg\/mL [110.1-1468.4\u2005pmol\/L]), and hyperprolactinemia (140\u2005ng\/mL [140\u2005\u00b5g\/L]; reference 4-25\u2005ng\/mL [4-25\u2005\u00b5g\/L]). Despite decades of evaluation, a unifying diagnosis was not established until genetic testing identified the pathogenic SETD2 variant. This case expands the endocrine phenotype of Luscan\u2013Lumish syndrome to include hypogonadotropic hypogonadism and hyperprolactinemia associated with a pituitary microadenoma, highlighting the importance of genetic evaluation in patients with rapid-onset severe obesity and multisystem disease.<\/jats:p>","DOI":"10.1210\/jcemcr\/luag248","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T11:56:12Z","timestamp":1790769372000},"source":"Crossref","is-referenced-by-count":0,"title":["Endocrine manifestations of Luscan\u2013Lumish syndrome associated with a novel SETD2 frameshift variant"],"prefix":"10.1210","volume":"4","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7986-971X","authenticated-orcid":false,"given":"Julia","family":"Huang","sequence":"first","affiliation":[{"name":"Division of Endocrinology, Los Angeles General Medical Center and Keck Medicine of USC , Los Angeles, CA 90033 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana","family":"Ashouri","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Los Angeles General Medical Center and Keck Medicine of USC , Los Angeles, CA 90033 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa Lampe","family":"Dominguez","sequence":"additional","affiliation":[{"name":"Division of Endocrinology, Los Angeles General Medical Center and Keck Medicine of USC , Los Angeles, CA 90033 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2026,10,5]]},"reference":[{"issue":"6","key":"2026100422271030900_luag248-B1","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.3390\/genes14061179","article-title":"Clinical heterogeneity in patients with SETD2 variants","volume":"14","author":"Parra","year":"2023","journal-title":"Genes (Basel)"},{"key":"2026100422271030900_luag248-B2","volume-title":"GeneReviews\u00ae","author":"Pappas","year":"2022"},{"issue":"4","key":"2026100422271030900_luag248-B3","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1002\/ajmg.c.31746","article-title":"SETD2-related overgrowth syndrome","volume":"181","author":"Marzin","year":"2019","journal-title":"Am J Med Genet C Semin Med Genet"},{"issue":"5","key":"2026100422271030900_luag248-B4","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med"},{"issue":"5","key":"2026100422271030900_luag248-B5","article-title":"SETD2: a role in cancer and beyond","volume":"7","author":"Fahey","year":"2017","journal-title":"Cold Spring Harb Perspect 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Metab"},{"issue":"10","key":"2026100422271030900_luag248-B9","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1016\/S2213-8587(25)00227-X","article-title":"Prolactinomas","volume":"13","author":"Fleseriu","year":"2025","journal-title":"Lancet Diabetes Endocrinol"},{"issue":"22","key":"2026100422271030900_luag248-B10","doi-asserted-by":"crossref","first-page":"3123","DOI":"10.1093\/hmg\/ddad079","article-title":"Epigenotype\u2013phenotype correlations in SETD2 disorders","volume":"32","author":"Lee","year":"2023","journal-title":"Hum Mol Genet"},{"issue":"3","key":"2026100422271030900_luag248-B11","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1210\/clinem\/dgaa893","article-title":"Enhanced growth hormone signaling in Luscan\u2013Lumish syndrome","volume":"106","author":"Suda","year":"2021","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"2026100422271030900_luag248-B12","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1210\/jc.2012-3550","article-title":"Approach to hypogonadotropic hypogonadism","volume":"98","author":"Silveira","year":"2013","journal-title":"J Clin Endocrinol Metab"}],"container-title":["JCEM Case 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