{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T10:42:00Z","timestamp":1789123320900,"version":"build-2803163510"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"2","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,8,1]]},"abstract":"<jats:sec>\n<jats:title>Context:<\/jats:title>\n<jats:p>Short stature in children is a common reason for referral to pediatric endocrinologists. The underlying cause of short stature remains unclear in many cases and patients often receive unsatisfactory, descriptive diagnoses. While textbooks underline the rarity of genetic causes of growth hormone (GH) insensitivity and the severity of its associated growth failure, increased genetic testing in patients with short stature of unclear origin has revealed gene defects in the GH\/insulin-like growth factor (IGF-I) axis associated with milder phenotypes. As such, heterozygous <jats:italic>IGF1<\/jats:italic> gene defects have been reported as a cause of mild and severe short stature. Here, we aimed to describe the clinical and hormonal profile of children with <jats:italic>IGF1<\/jats:italic> haploinsufficiency and their short-term response to growth hormone treatment (GHT).<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Case descriptions:<\/jats:title>\n<jats:p>We describe five patients presenting with short stature, microcephaly, and in four out of five born small for gestational age diagnosed with <jats:italic>IGF1<\/jats:italic> haploinsufficiency. The phenotype of these patients resembles that of previously described cases with similar gene defects. In our series, segregation of the short stature with the <jats:italic>IGF1<\/jats:italic> deletion is evident from the pedigrees and our data suggests a modest response to GHT.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions:<\/jats:title>\n<jats:p>This study is the first case series of complete heterozygous <jats:italic>IGF1<\/jats:italic> deletions in children. The specific genetic defects provide a clear image of the phenotype of <jats:italic>IGF1<\/jats:italic> haploinsufficiency \u2013 unbiased by heterozygous mutations with possible dominant negative effects on IGF-I function. We increase the evidence for <jats:italic>IGF1<\/jats:italic> haploinsufficiency as a cause of short stature, microcephaly, and SGA.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-20-1463","type":"journal-article","created":{"date-parts":[[2021,6,14]],"date-time":"2021-06-14T16:56:27Z","timestamp":1623689787000},"page":"323-332","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":4,"title":["IGF1 haploinsufficiency in children with short stature: a case series"],"prefix":"10.1093","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8259-3329","authenticated-orcid":true,"given":"Willem","family":"Staels","sequence":"first","affiliation":[{"name":"1Division of Pediatric Endocrinology, Department of Pediatrics, KidZ Health Castle, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium"},{"name":"2Division of Pediatric Endocrinology, Department of Pediatrics, Ghent University Hospital and Ghent University, Ghent, Belgium"},{"name":"3Belgian Society for Pediatric Endocrinology and Diabetology (BESPEED), Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nuriya","family":"Alev","sequence":"additional","affiliation":[{"name":"4Division of Pediatric Endocrinology, Department of Pediatrics, H\u00f4pital Universitaire des Enfants Reine Fabiola, Universit\u00e9 Libre de Bruxelles, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabelle","family":"Maystadt","sequence":"additional","affiliation":[{"name":"5Centre de Genetique Humaine, Institut de Pathologie et de Genetique, Charleroi, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olimpia","family":"Chivu","sequence":"additional","affiliation":[{"name":"3Belgian Society for Pediatric Endocrinology and Diabetology (BESPEED), Brussels, Belgium"},{"name":"6Department of Pediatrics, Clinique CHC MontL\u00e9gia, Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean","family":"De Schepper","sequence":"additional","affiliation":[{"name":"1Division of Pediatric Endocrinology, Department of Pediatrics, KidZ Health Castle, UZ Brussel, Vrije Universiteit Brussel, Brussels, Belgium"},{"name":"3Belgian Society for Pediatric Endocrinology and Diabetology (BESPEED), Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudine","family":"Heinrichs","sequence":"additional","affiliation":[{"name":"3Belgian Society for Pediatric Endocrinology and Diabetology (BESPEED), Brussels, Belgium"},{"name":"5Centre de Genetique Humaine, Institut de Pathologie et de Genetique, Charleroi, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"Beckers","sequence":"additional","affiliation":[{"name":"3Belgian Society for Pediatric Endocrinology and Diabetology (BESPEED), Brussels, Belgium"},{"name":"7Division of Pediatric Endocrinology, Department of Pediatrics, Universit\u00e9 Catholique de Louvain, CHU UCL Namur, Yvoir, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","container-title":["European Journal of Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/eje.bioscientifica.com\/view\/journals\/eje\/185\/2\/EJE-20-1463.xml","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/eje.bioscientifica.com\/downloadpdf\/journals\/eje\/185\/2\/EJE-20-1463.xml","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,2,14]],"date-time":"2023-02-14T16:16:12Z","timestamp":1676391372000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejendo\/article\/185\/2\/323\/6654326"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,1]]},"references-count":0,"journal-issue":{"issue":"2"},"URL":"https:\/\/doi.org\/10.1530\/eje-20-1463","relation":{},"ISSN":["0804-4643","1479-683X"],"issn-type":[{"value":"0804-4643","type":"print"},{"value":"1479-683X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,1]]}}}