{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T14:24:01Z","timestamp":1787927041874,"version":"build-2784847793"},"reference-count":39,"publisher":"The Endocrine Society","license":[{"start":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T00:00:00Z","timestamp":1786406400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100022431","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/X021173\/1"],"award-info":[{"award-number":["MR\/X021173\/1"]}],"id":[{"id":"10.13039\/501100022431","id-type":"DOI","asserted-by":"publisher"}]},{"name":"EpigenRare Medical Research Council Rare Diseases Node","award":["MR\/Y008170\/1"],"award-info":[{"award-number":["MR\/Y008170\/1"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Temple syndrome (TS14) is an imprinting disorder caused by abnormalities at chromosome 14q32.2. Its phenotype overlaps with Silver-Russell and Prader-Willi syndromes, contributing to underrecognition and delayed diagnosis. Its endocrine manifestations remain incompletely characterized.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To report the largest TS14 cohort to date to define the endocrine and clinical phenotype, evaluate management, response to GH therapy, and develop a novel TS14-specific clinical score.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Design<\/jats:title>\n                    <jats:p>Multicenter cohort study.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Setting<\/jats:title>\n                    <jats:p>Specialist centers in United Kingdom and The Netherlands.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Patients<\/jats:title>\n                    <jats:p>Seventy-one individuals with TS14.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Main outcome measure<\/jats:title>\n                    <jats:p>Endocrine and growth-related phenotypes, metabolic complications, and diagnostic performance of a scoring system.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Genetic subtypes included maternal uniparental disomy (52%), hypomethylation (41%), and deletion (6%). Most patients were born small for gestational age (68%); 73% had short stature at age 1 to 3 years, improving to 15% at age 11 to 14 years, with a greater improvement in those treated with GH. Baseline IGF-1 concentrations were \u2265\u22122 SD scores in all patients, whereas GH deficiency was confirmed in 27%. Early feeding difficulties affected 87%, 47% developed obesity, and 20% had hyperphagia. Dyslipidemia was present in 38% and central precocious puberty in 62%. Only 56.5% fulfilled \u22653 criteria of the Netchine-Harbison scoring system. We present a scoring system to identify which patients should be tested for TS14.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The endocrine phenotype of TS14 encompasses growth failure, GH deficiency, precocious puberty and disordered appetite, and requires age-specific management. Response to GH therapy was promising. A TS14-specific scoring system could enable earlier diagnosis and endocrine intervention, potentially improving outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgag327","type":"journal-article","created":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T06:05:06Z","timestamp":1786428306000},"source":"Crossref","is-referenced-by-count":0,"title":["Temple syndrome\u2014an underrecognized multisystem growth disorder: large cohort analysis and proposed scoring system"],"prefix":"10.1210","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7536-1183","authenticated-orcid":false,"given":"Alicia F","family":"Juriaans","sequence":"first","affiliation":[{"name":"Faculty of Medicine, University of Southampton , Southampton SO17 1BJ ,","place":["UK"]},{"name":"Department of Paediatrics, University Hospital Southampton , Southampton SO16 6YD ,","place":["UK"]},{"name":"Department of Paediatrics, Subdivision Paediatric Endocrinology, Erasmus University Medical Center , 3015 GD Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella","family":"Gazdagh","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Southampton , Southampton SO17 1BJ ,","place":["UK"]},{"name":"Wessex Clinical Genetics Service, Princess Anne Hospital, University Hospital Southampton NHS Foundation Trust , Southampton SO16 5YA ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I Karen","family":"Temple","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Southampton , Southampton SO17 1BJ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deborah J G","family":"Mackay","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Southampton , Southampton SO17 1BJ ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerthe F","family":"Kerkhof","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Subdivision Paediatric Endocrinology, Erasmus University Medical Center , 3015 GD Rotterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7560-6320","authenticated-orcid":false,"given":"Justin H","family":"Davies","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Southampton , Southampton SO17 1BJ ,","place":["UK"]},{"name":"Regional Centre for Paediatric Endocrinology, Southampton Children's Hospital , Southampton SO16 6YD ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2026,8,11]]},"reference":[{"issue":"8","key":"2026082809262468500_dgag327-B1","doi-asserted-by":"crossref","first-page":"511","DOI":"10.1136\/jmg.28.8.511","article-title":"Maternal uniparental disomy for chromosome 14","volume":"28","author":"Temple","year":"1991","journal-title":"J Med Genet"},{"issue":"12","key":"2026082809262468500_dgag327-B2","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1038\/gim.2017.53","article-title":"Temple syndrome: comprehensive molecular and clinical findings in 32 Japanese patients","volume":"19","author":"Kagami","year":"2017","journal-title":"Genet Med"},{"issue":"7","key":"2026082809262468500_dgag327-B3","doi-asserted-by":"crossref","first-page":"2436","DOI":"10.1210\/jc.2017-02152","article-title":"Chromosome 14q32.2 imprinted region disruption as an alternative molecular diagnosis of Silver-Russell syndrome","volume":"103","author":"Geoffron","year":"2018","journal-title":"J Clin Endocrinol Metab"},{"issue":"6","key":"2026082809262468500_dgag327-B4","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1111\/cge.13244","article-title":"Molecular and clinical studies in 8 patients with Temple syndrome","volume":"93","author":"Gillessen-Kaesbach","year":"2018","journal-title":"Clin Genet"},{"issue":"1","key":"2026082809262468500_dgag327-B5","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1002\/ajmg.a.38533","article-title":"Temple syndrome as a differential diagnosis to Prader-Willi syndrome: identifying three new patients","volume":"176","author":"Lande","year":"2018","journal-title":"Am J Med Genet A"},{"issue":"21","key":"2026082809262468500_dgag327-B6","doi-asserted-by":"crossref","first-page":"6289","DOI":"10.3390\/jcm11216289","article-title":"Temple syndrome: clinical findings, body composition and cognition in 15 patients","volume":"11","author":"Juriaans","year":"2022","journal-title":"J Clin Med"},{"issue":"3","key":"2026082809262468500_dgag327-B7","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1111\/j.1365-2265.2008.03228.x","article-title":"Randomized controlled GH trial: effects on anthropometry, body composition and body proportions in a large group of children with Prader-Willi syndrome","volume":"69","author":"Festen","year":"2008","journal-title":"Clin Endocrinol (Oxf)"},{"issue":"2","key":"2026082809262468500_dgag327-B8","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1038\/nrendo.2016.138","article-title":"Diagnosis and management of Silver-Russell syndrome: first international consensus statement","volume":"13","author":"Wakeling","year":"2017","journal-title":"Nat Rev Endocrinol"},{"issue":"9","key":"2026082809262468500_dgag327-B9","doi-asserted-by":"crossref","first-page":"e3041","DOI":"10.1210\/clinem\/dgae883","article-title":"Temple syndrome: comprehensive clinical study in genetically confirmed 60 Japanese patients","volume":"110","author":"Ogawa","year":"2025","journal-title":"J Clin Endocrinol Metab"},{"issue":"8","key":"2026082809262468500_dgag327-B10","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1136\/jmedgenet-2014-102396","article-title":"Temple syndrome: improving the recognition of an underdiagnosed chromosome 14 imprinting disorder: an analysis of 51 published cases","volume":"51","author":"Ioannides","year":"2014","journal-title":"J Med Genet"},{"issue":"6","key":"2026082809262468500_dgag327-B11","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1159\/000496700","article-title":"Growth hormone improves short-term growth in patients with temple syndrome","volume":"90","author":"Brightman","year":"2018","journal-title":"Horm Res Paediatr"},{"issue":"5","key":"2026082809262468500_dgag327-B12","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1159\/000530420","article-title":"The effects of 5 years of growth hormone treatment on growth and body composition in patients with temple syndrome","volume":"96","author":"Juriaans","year":"2023","journal-title":"Horm Res Paediatr"},{"issue":"8","key":"2026082809262468500_dgag327-B13","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1038\/ejhg.2017.91","article-title":"New insights into the imprinted MEG8-DMR in 14q32 and clinical and molecular description of novel patients with temple syndrome","volume":"25","author":"Beygo","year":"2017","journal-title":"Eur J Hum Genet"},{"issue":"2","key":"2026082809262468500_dgag327-B14","doi-asserted-by":"crossref","first-page":"eaau9425","DOI":"10.1126\/sciadv.aau9425","article-title":"Transcriptional profiling at the DLK1\/MEG3 domain explains clinical overlap between imprinting disorders","volume":"5","author":"Abi Habib","year":"2019","journal-title":"Sci Adv"},{"issue":"8","key":"2026082809262468500_dgag327-B15","doi-asserted-by":"crossref","first-page":"1990","DOI":"10.1002\/ajmg.a.33530","article-title":"Investigation of 90 patients referred for molecular cytogenetic analysis using aCGH uncovers previously unsuspected anomalies of imprinting","volume":"152A","author":"Poole","year":"2010","journal-title":"Am J Med Genet A"},{"key":"2026082809262468500_dgag327-B16","doi-asserted-by":"crossref","first-page":"102201","DOI":"10.1016\/j.fsigen.2019.102201","article-title":"Reverse complement PCR: a novel one-step PCR system for typing highly degraded DNA for human identification","volume":"44","author":"Kieser","year":"2020","journal-title":"Forensic Sci Int Genet"},{"issue":"7","key":"2026082809262468500_dgag327-B17","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1136\/jmedgenet-2014-102979","article-title":"A prospective study validating a clinical scoring system and demonstrating phenotypical-genotypical correlations in Silver-Russell syndrome","volume":"52","author":"Azzi","year":"2015","journal-title":"J Med Genet"},{"issue":"1","key":"2026082809262468500_dgag327-B18","doi-asserted-by":"crossref","first-page":"8086","DOI":"10.1038\/ncomms9086","article-title":"Mutations in NLRP5 are associated with reproductive wastage and multilocus imprinting disorders in humans","volume":"6","author":"Docherty","year":"2015","journal-title":"Nat Commun"},{"issue":"6","key":"2026082809262468500_dgag327-B19","doi-asserted-by":"crossref","first-page":"1896","DOI":"10.1002\/ajmg.a.62717","article-title":"A patient with multilocus imprinting disturbance involving hypomethylation at 11p15 and 14q32, and phenotypic features of Beckwith-Wiedemann and Temple syndromes","volume":"188","author":"Grosvenor","year":"2022","journal-title":"Am J Med Genet A"},{"issue":"6","key":"2026082809262468500_dgag327-B20","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1136\/jmedgenet-2021-107699","article-title":"Whole-genome analysis as a diagnostic tool for patients referred for diagnosis of Silver-Russell syndrome: a real-world study","volume":"59","author":"Alhendi","year":"2022","journal-title":"J Med Genet"},{"issue":"7","key":"2026082809262468500_dgag327-B21","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1038\/oby.2007.216","article-title":"Assessment of hyperphagia in Prader-Willi syndrome","volume":"15","author":"Dykens","year":"2007","journal-title":"Obesity (Silver Spring)"},{"issue":"2","key":"2026082809262468500_dgag327-B22","doi-asserted-by":"crossref","first-page":"251","DOI":"10.2169\/internalmedicine.2743-23","article-title":"A male Japanese patient with Temple syndrome complicated by type 2 diabetes mellitus","volume":"64","author":"Iwanishi","year":"2024","journal-title":"Intern Med"},{"issue":"1","key":"2026082809262468500_dgag327-B23","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1002\/ajmg.10511","article-title":"Maternal isodisomy for 14q21-q24 in a man with diabetes mellitus","volume":"111","author":"Kayashima","year":"2002","journal-title":"Am J Med Genet"},{"issue":"5","key":"2026082809262468500_dgag327-B24","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1034\/j.1399-0004.2000.570514.x","article-title":"A patient with maternal chromosome 14 UPD presenting with a mild phenotype and MODY","volume":"57","author":"Manzoni","year":"2000","journal-title":"Clin Genet"},{"issue":"19","key":"2026082809262468500_dgag327-B25","doi-asserted-by":"crossref","first-page":"2039","DOI":"10.1002\/ajmg.a.31414","article-title":"Is there a higher incidence of maternal uniparental disomy 14 [UPD(14)mat]? Detection of 10 new patients by methylation-specific PCR","volume":"140","author":"Mitter","year":"2006","journal-title":"Am J Med Genet"},{"issue":"1","key":"2026082809262468500_dgag327-B26","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1002\/ajmg.a.37346","article-title":"New patients with Temple syndrome caused by 14q32 deletion: genotype-phenotype correlations and risk of thyroid cancer","volume":"170A","author":"Severi","year":"2016","journal-title":"Am J Med Genet A"},{"key":"2026082809262468500_dgag327-B27"},{"key":"2026082809262468500_dgag327-B28"},{"key":"2026082809262468500_dgag327-B29","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/bs.adgen.2025.03.001","article-title":"Prader Willi syndrome: advances in genetics","volume":"113","author":"Hingar","year":"2025","journal-title":"Adv Genet"},{"issue":"10","key":"2026082809262468500_dgag327-B30","doi-asserted-by":"crossref","first-page":"683","DOI":"10.1136\/jmedgenet-2019-106561","article-title":"Phenotype of genetically confirmed Silver-Russell syndrome beyond childhood","volume":"57","author":"Lokulo-Sodipe","year":"2020","journal-title":"J Med Genet"},{"issue":"3","key":"2026082809262468500_dgag327-B31","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1210\/endrev\/bnad002","article-title":"International consensus guideline on small for gestational age: etiology and management from infancy to early adulthood","volume":"44","author":"Hokken-Koelega","year":"2023","journal-title":"Endocr Rev"},{"issue":"7","key":"2026082809262468500_dgag327-B32","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1210\/jc.2012-1182","article-title":"Beneficial effects of growth hormone treatment on cognition in children with Prader-Willi syndrome: a randomized controlled trial and longitudinal study","volume":"97","author":"Siemensma","year":"2012","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"2026082809262468500_dgag327-B33","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1530\/EJE-19-0479","article-title":"Cognitive functioning in children with Prader-Willi syndrome during 8 years of growth hormone treatment","volume":"182","author":"Donze","year":"2020","journal-title":"Eur J Endocrinol"},{"issue":"8","key":"2026082809262468500_dgag327-B34","doi-asserted-by":"crossref","first-page":"3041","DOI":"10.1210\/jc.2015-1410","article-title":"IGF-1 levels, complex formation, and IGF bioactivity in growth hormone-treated children with Prader-Willi syndrome","volume":"100","author":"Bakker","year":"2015","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2026082809262468500_dgag327-B35","first-page":"1515","article-title":"Silver-Russell syndrome and free insulin-like growth factor-1 measurements","volume":"8","author":"Oude Engberink","year":"2024","journal-title":"J Endocr Soc"},{"issue":"10","key":"2026082809262468500_dgag327-B36","doi-asserted-by":"crossref","first-page":"4600","DOI":"10.1210\/jc.2009-1831","article-title":"Elevated insulin-like growth factor-I values in children with Prader-Willi syndrome compared with growth hormone (GH) deficiency children over two years of GH treatment","volume":"95","author":"Feigerlova","year":"2010","journal-title":"J Clin Endocrinol Metab"},{"issue":"5","key":"2026082809262468500_dgag327-B37","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.3390\/jcm11051280","article-title":"Free insulin-like growth factor (IGF)-I in children with PWS","volume":"11","author":"Damen","year":"2022","journal-title":"J Clin Med"},{"issue":"11","key":"2026082809262468500_dgag327-B38","doi-asserted-by":"crossref","first-page":"e2001","DOI":"10.1210\/clinem\/dgae074","article-title":"Body composition and metabolism in adults with molecularly confirmed Silver-Russell syndrome","volume":"109","author":"Lokulo-Sodipe","year":"2024","journal-title":"J Clin Endocrinol Metab"},{"issue":"1","key":"2026082809262468500_dgag327-B39","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1186\/s13148-025-02023-7","article-title":"Silver-Russell syndrome secondary to rare (epi)genotypes exhibits phenotypic heterogeneity challenging clinical diagnosis","volume":"17","author":"Kurup","year":"2025","journal-title":"Clin Epigenetics"}],"container-title":["The Journal of Clinical Endocrinology &amp; Metabolism"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgag327\/70606932\/dgag327.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article-pdf\/doi\/10.1210\/clinem\/dgag327\/70606932\/dgag327.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T13:30:48Z","timestamp":1787923848000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jcem\/advance-article\/doi\/10.1210\/clinem\/dgag327\/8758664"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,11]]},"references-count":39,"URL":"https:\/\/doi.org\/10.1210\/clinem\/dgag327","relation":{},"ISSN":["0021-972X","1945-7197"],"issn-type":[{"value":"0021-972X","type":"print"},{"value":"1945-7197","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,11]]},"article-number":"dgag327"}}