{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T08:07:56Z","timestamp":1789546076648,"version":"build-2803163510"},"reference-count":16,"publisher":"The Endocrine Society","issue":"10","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":13,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"NIHR","doi-asserted-by":"publisher","award":["NIHR3044587"],"award-info":[{"award-number":["NIHR3044587"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,9,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Zhu\u2013Tokita\u2013Takenouchi\u2013Kim (ZTTK) syndrome is a rare multisystem developmental disorder caused by heterozygous pathogenic variants in SON. Short stature is common, but data on endocrine function and response to recombinant human growth hormone (rhGH) are limited. We describe a female child with genetically confirmed ZTTK syndrome presenting with profound proportionate short stature, hypotonia, and developmental delay. Insulin-like growth factor 1 (IGF-1) of 91\u2005ng\/mL (Systeme international [SI]: 11.9\u2005nmol\/L; reference range, 33.6-170.5\u2005ng\/mL [SI: 4.4-22.3\u2005nmol\/L]) was normal, and peak growth hormone (GH) concentration on arginine stimulation testing was 7.2\u2005ng\/mL (SI: 21.6 mIU\/L], above the UK diagnostic cutoff for GH deficiency (&amp;lt;6.7\u2005ng\/mL [SI: &amp;lt;20.1 mIU\/L]). Given severely impaired linear growth and declining height velocity, a monitored trial of rhGH was initiated. Treatment with rhGH (0.035\u2005mg\/kg\/day) resulted in &amp;gt;50% increase in height velocity from baseline (4.3-7.2\u2005cm\/year), suggesting a good response to rhGH, with sustained improvement over 2 years (height standard deviation score \u22124.16 to \u22123.40). Insulin-like growth factor 1, thyroid function, glucose, and glycated hemoglobin A1c remained normal. No adverse effects were observed. This case demonstrates a clinically significant growth response to rhGH in ZTTK syndrome despite absence of biochemical GH deficiency, supporting a supervised 12-month therapeutic trial.<\/jats:p>","DOI":"10.1210\/jcemcr\/luag247","type":"journal-article","created":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T11:19:49Z","timestamp":1786965589000},"source":"Crossref","is-referenced-by-count":0,"title":["Growth outcomes following recombinant human growth hormone therapy in Zhu\u2013Tokita\u2013Takenouchi\u2013Kim syndrome"],"prefix":"10.1210","volume":"4","author":[{"given":"Shien Chen","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Paediatric Endocrinology and Diabetes, Birmingham Children's Hospital , Birmingham B46 NH ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusef","family":"Muflihi","sequence":"additional","affiliation":[{"name":"Department of Paediatric Endocrinology and Diabetes, Birmingham Children's Hospital , Birmingham B46 NH ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1337-7889","authenticated-orcid":false,"given":"Zainaba","family":"Mohammed","sequence":"additional","affiliation":[{"name":"Department of Paediatric Endocrinology and Diabetes, Birmingham Children's Hospital , Birmingham B46 NH ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Kinning","sequence":"additional","affiliation":[{"name":"West Midlands Regional Clinical Genetics Service, Birmingham Women's Hospital , Birmingham B15 2TG ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5743-1077","authenticated-orcid":false,"given":"Renuka P","family":"Dias","sequence":"additional","affiliation":[{"name":"Department of Paediatric Endocrinology and Diabetes, Birmingham Children's Hospital , Birmingham B46 NH ,","place":["UK"]},{"name":"Department of Immunology and Immunotherapy, College of Medicine and Health, University of Birmingham, Birmingham B15 2TT ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"issue":"3","key":"2026091603520417500_luag247-B1","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/s41431-021-00960-4","article-title":"Establishing the phenotypic spectrum of ZTTK syndrome by analysis of 52 individuals with variants in SON","volume":"30","author":"Dingemans","year":"2022","journal-title":"Eur J Hum Genet"},{"issue":"10","key":"2026091603520417500_luag247-B2","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1038\/gim.2014.191","article-title":"Whole-exome sequencing in undiagnosed genetic diseases: interpreting 119 trios","volume":"17","author":"Zhu","year":"2015","journal-title":"Genet Med"},{"key":"2026091603520417500_luag247-B3","author":"ZTTK SON-Shine FOUNDATION"},{"issue":"2","key":"2026091603520417500_luag247-B4","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1159\/000546621","article-title":"A novel SON gene variant associated with rare clinical features in ZTTK syndrome: a case report and literature review","volume":"17","author":"Ates","year":"2026","journal-title":"Mol Syndromol"},{"issue":"2","key":"2026091603520417500_luag247-B5","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.molcel.2011.03.014","article-title":"SON controls cell-cycle progression by coordinated regulation of RNA splicing","volume":"42","author":"Ahn","year":"2011","journal-title":"Mol Cell"},{"key":"2026091603520417500_luag247-B6","volume-title":"GeneReviews","author":"Mori","year":"1993"},{"issue":"3","key":"2026091603520417500_luag247-B7","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1111\/pde.14113","article-title":"Skin and nails abnormalities in a patient with ZTTK syndrome and a de novo mutation in SON","volume":"37","author":"Quintana Castanedo","year":"2020","journal-title":"Pediatr Dermatol"},{"key":"2026091603520417500_luag247-B8","author":"Ha"},{"key":"2026091603520417500_luag247-B9","author":"BSPED Growth Disorders Special Interest Group"},{"key":"2026091603520417500_luag247-B10","author":"National Institute for Health and Care Excellence"},{"issue":"8","key":"2026091603520417500_luag247-B11","doi-asserted-by":"crossref","DOI":"10.1002\/mgg3.2188","article-title":"Expanding the mutational spectrum of ZTTK syndrome: a de novo variant with global developmental delay and malnutrition in a Chinese patient","volume":"11","author":"Tang","year":"2023","journal-title":"Mol Genet Genomic Med"},{"issue":"3","key":"2026091603520417500_luag247-B12","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.ajhg.2016.06.035","article-title":"De novo truncating variants in SON cause intellectual disability, congenital malformations, and failure to thrive","volume":"99","author":"Tokita","year":"2016","journal-title":"Am J Hum Genet"},{"issue":"11","key":"2026091603520417500_luag247-B13","doi-asserted-by":"crossref","first-page":"1416","DOI":"10.1002\/pd.6658","article-title":"Agenesis of corpus callosum, malformations of cortical development, duodenal atresia and fetal growth restriction: prenatal markers for Zhu-Tokita-Takenouchi-Kim syndrome","volume":"44","author":"Carmant","year":"2024","journal-title":"Prenat Diagn"},{"issue":"11","key":"2026091603520417500_luag247-B14","doi-asserted-by":"crossref","DOI":"10.1002\/mgg3.1496","article-title":"A de novo heterozygous variant in the SON gene is associated with Zhu-Tokita-Takenouchi-Kim syndrome","volume":"8","author":"Yang","year":"2020","journal-title":"Mol Genet Genomic Med"},{"issue":"11","key":"2026091603520417500_luag247-B15","doi-asserted-by":"crossref","first-page":"1660","DOI":"10.3174\/ajnr.A7663","article-title":"Distinctive brain malformations in 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