{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T04:06:06Z","timestamp":1776830766930,"version":"3.51.2"},"reference-count":12,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,3,8]],"date-time":"2024-03-08T00:00:00Z","timestamp":1709856000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Germline gain of function variations in the <jats:italic>AKT3<\/jats:italic> gene cause brain overgrowth syndrome with megalencephaly and diffuse bilateral cortical malformations. Here we report a child with megalencephaly, who is a carrier of a novel heterozygous missense variant in the <jats:italic>AKT3<\/jats:italic> gene NM_005465.7:c.964G&gt;T,p.Asp322Tyr. The phenotype of this patient is associated with pituitary deficiencies diagnosed at 2\u2009years of age: growth hormone (GH) deficiency responsible for growth delay and central hypothyroidism. After 6\u2009months of GH treatment, intracranial hypertension was noted, confirmed by the observation of papilledema and increased intracranial pressure, requiring the initiation of acetazolamide treatment and the discontinuation of GH treatment. This is the second reported patient described with megalencephaly and <jats:italic>AKT3<\/jats:italic> gene variant associated with GH deficiency . Other endocrine disorders have also been reported in few cases with hypothyroidism and hypoglycemia. Pituitary deficiency may be a part of the of megalencephaly phenotype secondary to germline variant in the <jats:italic>AKT3<\/jats:italic> gene. Special attention should be paid to growth in these patients and search for endocrine deficiency is necessary in case of growth retardation or hypoglycemia.<\/jats:p>","DOI":"10.1002\/ajmg.a.63585","type":"journal-article","created":{"date-parts":[[2024,3,9]],"date-time":"2024-03-09T04:23:42Z","timestamp":1709958222000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Megalencephaly secondary to a novel germline missense variant <scp>p.Asp322Tyr<\/scp> in <i>AKT3<\/i> associated with growth hormone deficiency and central hypothyroidism: A case report"],"prefix":"10.1002","volume":"194","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6620-6568","authenticated-orcid":false,"given":"E.","family":"Renard","sequence":"first","affiliation":[{"name":"Pediatric Endocrinology Unit, Department of Pediatrics University Hospital of Nancy  Nancy France"},{"name":"INSERM UMR_S 1256, Nutrition, Genetics, and Environmental Risk Exposure (NGERE), Faculty of Medicine of Nancy University of Lorraine  Nancy France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6799-0438","authenticated-orcid":false,"given":"C.","family":"Bonnet","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 1256, Nutrition, Genetics, and Environmental Risk Exposure (NGERE), Faculty of Medicine of Nancy University of Lorraine  Nancy France"},{"name":"Genetics Laboratory University Hospital of Nancy  Nancy France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Di Patrizio","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Unit, Department of Pediatrics University Hospital of Nancy  Nancy France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"E.","family":"Schmitt","sequence":"additional","affiliation":[{"name":"Department of Neuroradiology University Hospital of Nancy  Nancy France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A. C.","family":"Madkaud","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University Hospital of Nancy  Nancy France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C.","family":"Chabot","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology Unit, Department of Pediatrics University Hospital of Nancy  Nancy France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Kuchenbuch","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology University Hospital of Nancy  Nancy France"},{"name":"University of Lorraine  Nancy France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L.","family":"Lambert","sequence":"additional","affiliation":[{"name":"INSERM UMR_S 1256, Nutrition, Genetics, and Environmental Risk Exposure (NGERE), Faculty of Medicine of Nancy University of Lorraine  Nancy France"},{"name":"Department of Clinical Genetics University Hospital of Nancy  Nancy France"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,3,8]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awx203"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/4682876"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182a55f17"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awv045"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.62338"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41439-022-00197-7"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2014.11.018"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2331"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1054\/ghir.2001.0203"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.38099"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbior.2014.04.001"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.63585","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,7]],"date-time":"2024-06-07T15:29:46Z","timestamp":1717774186000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.63585"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,3,8]]},"references-count":12,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["10.1002\/ajmg.a.63585"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.63585","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,3,8]]},"assertion":[{"value":"2023-09-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-02-24","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-03-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e63585"}}