{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:30:54Z","timestamp":1790195454825,"version":"4.1.0"},"reference-count":24,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T00:00:00Z","timestamp":1619049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>Hypomethylation of H19 and IGF2 can cause Silver\u2013Russell syndrome (SRS), a clinically and genetically heterogeneous condition characterized by intrauterine growth restriction, poor postnatal growth, relative macrocephaly, craniofacial abnormalities, body asymmetry, hypoglycemia and feeding difficulties. Isolated hypomethylation of IGF2 has been reported in single cases of SRS as well. Here, we report on a 19-month-old patient who presented with two episodes of hypoglycemic seizures. No intrauterine growth restriction was observed, the patient did not present with SRS-typical facial features, and postnatal growth in the first months of life was along the lower normal percentiles. Exome sequencing did not reveal any likely pathogenic variants explaining the phenotype; however, hypomethylation studies revealed isolated hypomethylation of IGF2, while the methylation of H19 appeared normal. Hypoglycemia responded well to growth hormone therapy, and the boy showed good catch-up growth. Our case demonstrates that SRS and isolated IGF2 hypomethylation should be considered early in the diagnosis of recurrent hypoglycemia in childhood, especially in combination with small gestational age and poor growth.<\/jats:p>","DOI":"10.3390\/diagnostics11050749","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T13:59:14Z","timestamp":1619099954000},"page":"749","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Isolated Hypomethylation of IGF2 Associated with Severe Hypoglycemia Responsive to Growth Hormone Treatment"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5986-0468","authenticated-orcid":false,"given":"Sarah C.","family":"Gr\u00fcnert","sequence":"first","affiliation":[{"name":"Department of General Paediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Centre\u2014University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Uta","family":"Matysiak","sequence":"additional","affiliation":[{"name":"Department of General Paediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Centre\u2014University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franka","family":"Hodde","sequence":"additional","affiliation":[{"name":"Department of General Paediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Centre\u2014University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunda","family":"Ruzaike","sequence":"additional","affiliation":[{"name":"Department of General Paediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Centre\u2014University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekkehart","family":"Lausch","sequence":"additional","affiliation":[{"name":"Department of General Paediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Centre\u2014University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anke","family":"Schumann","sequence":"additional","affiliation":[{"name":"Department of General Paediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Centre\u2014University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natascha","family":"van der Werf-Grohmann","sequence":"additional","affiliation":[{"name":"Department of General Paediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Centre\u2014University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ute","family":"Spiekerkoetter","sequence":"additional","affiliation":[{"name":"Department of General Paediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Centre\u2014University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1714-6749","authenticated-orcid":false,"given":"Miriam","family":"Schmidts","sequence":"additional","affiliation":[{"name":"Department of General Paediatrics, Adolescent Medicine and Neonatology, Faculty of Medicine, Medical Centre\u2014University of Freiburg, 79106 Freiburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,4,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"604","DOI":"10.1086\/502981","article-title":"Hypomethylation of the H19 gene causes not only Silver-Russell syndrome (SRS) but also isolated asymmetry or an SRS-like phenotype","volume":"78","author":"Bliek","year":"2006","journal-title":"Am. 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