{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:00:07Z","timestamp":1760238007790,"version":"build-2065373602"},"reference-count":14,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Technology, Executive Yuan","award":["MOST-111-2811-B-195-001","MOST-110-2314-B-195-010-MY3","MOST-110-2314-B-195-014","MOST-110-2314-B-195-029","MMH-E-111-13","MMH-E-110-16","MMH-E-109-16","MMH-E-108-16"],"award-info":[{"award-number":["MOST-111-2811-B-195-001","MOST-110-2314-B-195-010-MY3","MOST-110-2314-B-195-014","MOST-110-2314-B-195-029","MMH-E-111-13","MMH-E-110-16","MMH-E-109-16","MMH-E-108-16"]}]},{"name":"MacKay Memorial Hospital","award":["MOST-111-2811-B-195-001","MOST-110-2314-B-195-010-MY3","MOST-110-2314-B-195-014","MOST-110-2314-B-195-029","MMH-E-111-13","MMH-E-110-16","MMH-E-109-16","MMH-E-108-16"],"award-info":[{"award-number":["MOST-111-2811-B-195-001","MOST-110-2314-B-195-010-MY3","MOST-110-2314-B-195-014","MOST-110-2314-B-195-029","MMH-E-111-13","MMH-E-110-16","MMH-E-109-16","MMH-E-108-16"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Costello syndrome (CS) is a type of RASopathy caused mainly by de-novo heterozygous pathogenic variants in the HRAS gene located on chromosome 11p15.5. The phenotype of CS is characterized by prenatal overgrowth, postnatal failure to thrive, curly or sparse fine hair, coarse facial features, and multisystem involvement, including cardiovascular, endocrine, and gastroenterological disorders. We present a one-year-old girl with rapid weight loss and severe failure to thrive. She had gastroesophageal reflux at the age of four months with subsequent rapid weight loss. The loss of fat tissue over the whole body, refractory to a hypercaloric diet, mimicked the presentation of progressive lipodystrophy and masked the dysmorphic features of CS. The final diagnosis of CS was made by whole exome sequencing, which demonstrated a hot-spot, heterozygouspathogenic variant in the HRAS gene (c.34G &gt; A, rs104894229). Our patient illustrates that the excessive energy needs in CS patients may lead to severe failure to thrive and cause challenges in diagnosing CS. This case also highlights the importance of recognizing CS in patients with a history of prenatal overgrowth, polyhydramnios presenting with severe failure to thrive refractory to pharmacotherapy and tube feeding.<\/jats:p>","DOI":"10.3390\/children9060905","type":"journal-article","created":{"date-parts":[[2022,6,17]],"date-time":"2022-06-17T01:48:12Z","timestamp":1655430492000},"page":"905","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rapid Weight Loss and Severe Failure to Thrive Mimicking Lipodystrophy Syndrome in a 1-Year-Old Taiwanese Girl with Costello Syndrome"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7530-5499","authenticated-orcid":false,"given":"Yu-Min","family":"Syu","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Far Eastern Memorial Hospital, New Taipei City 22021, Taiwan"},{"name":"Division of Genetics and Metabolism, Department of Pediatrics, MacKay Memorial Hospital, Taipei 10449, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hung-Chang","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Nutrition, Department of Pediatrics, MacKay Children\u2019s Hospital, Taipei 10449, Taiwan"},{"name":"Department of Medicine, MacKay Medical College, New Taipei City 25245, Taiwan"},{"name":"Department of Pediatrics, MacKay Children\u2019s Hospital, Taipei 10449, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jui-Hsing","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Medicine, MacKay Medical College, New Taipei City 25245, Taiwan"},{"name":"Department of Pediatrics, MacKay Children\u2019s Hospital, Taipei 10449, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chung-Lin","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Genetics and Metabolism, Department of Pediatrics, MacKay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Department of Rare Disease Center, MacKay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Institute of Clinical Medicine, National Yang-Ming Chiao Tung University, Taipei 11221, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9776-2092","authenticated-orcid":false,"given":"Chih-Kuang","family":"Chuang","sequence":"additional","affiliation":[{"name":"Division of Genetics and Metabolism, Department of Medical Research, MacKay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"College of Medicine, Fu-Jen Catholic University, Taipei 24205, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huei-Ching","family":"Chiu","sequence":"additional","affiliation":[{"name":"Division of Genetics and Metabolism, Department of Pediatrics, MacKay Memorial Hospital, Taipei 10449, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ya-Hui","family":"Chang","sequence":"additional","affiliation":[{"name":"Division of Genetics and Metabolism, Department of Pediatrics, MacKay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Department of Rare Disease Center, MacKay Memorial Hospital, Taipei 10449, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9619-0990","authenticated-orcid":false,"given":"Hsiang-Yu","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Genetics and Metabolism, Department of Pediatrics, MacKay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Department of Medicine, MacKay Medical College, New Taipei City 25245, Taiwan"},{"name":"Department of Rare Disease Center, MacKay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Division of Genetics and Metabolism, Department of Medical Research, MacKay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Department of Childhood Care and Education, MacKay Junior College of Medicine, Nursing and Management, Taipei 11260, Taiwan"},{"name":"Department of Medical Research, China Medical University Hospital, China Medical University, Taichung 40402, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuan-Pei","family":"Lin","sequence":"additional","affiliation":[{"name":"Division of Genetics and Metabolism, Department of Pediatrics, MacKay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Department of Medicine, MacKay Medical College, New Taipei City 25245, Taiwan"},{"name":"Department of Rare Disease Center, MacKay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Division of Genetics and Metabolism, Department of Medical Research, MacKay Memorial Hospital, Taipei 10449, Taiwan"},{"name":"Department of Infant and Child Care, National Taipei University of Nursing and Health Sciences, Taipei 11219, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1055\/s-0034-1377028","article-title":"Early postnatal diagnosis of Costello syndrome","volume":"227","author":"Kargl","year":"2014","journal-title":"Klin. Padiatr."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1002\/ajmg.a.61429","article-title":"Cardiac manifestations and gene mutations of patients with RASopathies in Taiwan","volume":"182","author":"Lee","year":"2020","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2692","DOI":"10.1002\/ajmg.a.35534","article-title":"Normative growth charts for individuals with Costello syndrome","volume":"158A","author":"Sammon","year":"2012","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/gim.2015.30","article-title":"Standards and guidelines for the interpretation of sequence variants: A joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology","volume":"17","author":"Richards","year":"2015","journal-title":"Genet Med."},{"key":"ref_5","unstructured":"Adam, M.P., Ardinger, H.H., Pagon, R.A., Wallace, S.E., Bean, L.J.H., Gripp, K.W., and Anemiya, A. (2006). Costello Syndrome. GeneReviews, University of Washington."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1210\/er.2017-00232","article-title":"The RASopathy Family: Consequences of Germline Activation of the RAS\/MAPK Pathway","volume":"39","author":"Tajan","year":"2018","journal-title":"Endocr. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1083","DOI":"10.1002\/ajmg.a.35292","article-title":"Prevalence and clinical features of Costello syndrome and cardio-facio-cutaneous syndrome in Japan: Findings from a nationwide epidemiological survey","volume":"158A","author":"Abe","year":"2012","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1002\/ajmg.a.61270","article-title":"Costello syndrome: Clinical phenotype, genotype, and management guidelines","volume":"179","author":"Gripp","year":"2019","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1007\/s00431-007-0558-0","article-title":"Costello syndrome: Clinical diagnosis in the first year of life","volume":"167","author":"Digilio","year":"2008","journal-title":"Eur. J. Pediatr."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1002\/ajmg.a.33857","article-title":"Clinical, pathological, and molecular analyses of cardiovascular abnormalities in Costello syndrome: A Ras\/MAPK pathway syndrome","volume":"155","author":"Lin","year":"2011","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2797","DOI":"10.1002\/ajmg.a.61812","article-title":"Impact of Costello syndrome on growth patterns","volume":"182","author":"Leoni","year":"2020","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/j.ejmg.2016.10.001","article-title":"Before and after\u2014Nutritional transformation of dysmorphism in a case of Costello syndrome","volume":"59","author":"Chiu","year":"2016","journal-title":"Eur. J. Med. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1016\/j.jpeds.2015.11.076","article-title":"Understanding Growth Failure in Costello Syndrome: Increased Resting Energy Expenditure","volume":"170","author":"Leoni","year":"2016","journal-title":"J. Pediatr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"4500","DOI":"10.1210\/jc.2016-2466","article-title":"The Diagnosis and Management of Lipodystrophy Syndromes: A Multi-Society Practice Guideline","volume":"101","author":"Brown","year":"2016","journal-title":"J. Clin. Endocrinol. Metab."}],"container-title":["Children"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2227-9067\/9\/6\/905\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:33:10Z","timestamp":1760139190000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2227-9067\/9\/6\/905"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,16]]},"references-count":14,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2022,6]]}},"alternative-id":["children9060905"],"URL":"https:\/\/doi.org\/10.3390\/children9060905","relation":{},"ISSN":["2227-9067"],"issn-type":[{"type":"electronic","value":"2227-9067"}],"subject":[],"published":{"date-parts":[[2022,6,16]]}}}