{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:54:07Z","timestamp":1760576047295,"version":"build-2065373602"},"reference-count":11,"publisher":"Ordem dos Medicos","license":[{"start":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:00:00Z","timestamp":1760486400000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Med Port"],"abstract":"<jats:p>Complex diseases arise from the interplay of genetic and environmental factors. We present a case where complex diseases seem to coexist. A 12-month-old girl was referred for short stature and hypotonia. Initial evaluation revealed central hypothyroidism, growth hormone deficiency and a small pituitary gland with ectopic neurohypophysis. Replacement therapy improved growth, but developmental delay and strabismus ensued. At age 10, she experienced a first seizure treated with levetiracetam. At age 12, she presented diabetic ketoacidosis and functional insulin therapy was started; positive autoantibodies confirmed autoimmune etiology. Initial genetic testing performed by microarray analysis retrieved normal results, but exome sequencing revealed a heterozygous pathogenic variant in KANSL1 gene, allowing for the diagnosis of Koolen-de Vries syndrome. In this patient, Koolen-de Vries syndrome presented initially as hypopituitarism and only later epilepsy. Afterwards, type 1 diabetes mellitus ensued, highlighting the complexity of intertwined conditions.<\/jats:p>","DOI":"10.20344\/amp.22709","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T15:53:32Z","timestamp":1760543612000},"source":"Crossref","is-referenced-by-count":0,"title":["A Complex Case of Koolen-De Vries Syndrome Associated with Hypopituitarism and Type 1 Diabetes Mellitus"],"prefix":"10.20344","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3415-6487","authenticated-orcid":false,"given":"Mafalda","family":"F\u00e9lix Cabral","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5181-3595","authenticated-orcid":false,"given":"Francisco","family":"Branco Caetano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1430-1122","authenticated-orcid":false,"given":"Carla","family":"Concei\u00e7\u00e3o","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6876-1688","authenticated-orcid":false,"given":"Diana","family":"Oliveira Antunes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1216-9279","authenticated-orcid":false,"given":"Lurdes","family":"Lopes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"8464","published-online":{"date-parts":[[2025,10,15]]},"reference":[{"key":"10725","doi-asserted-by":"crossref","unstructured":"Koolen DA, Vissers LE, Pfundt R, de Leeuw N, Knight SJ, Regan R, et al. A new chromosome 17q21.31 microdeletion syndrome associated with a common inversion polymorphism. Nat Genet. 2006;38:999-1001.","DOI":"10.1038\/ng1853"},{"key":"10726","doi-asserted-by":"crossref","unstructured":"Colin F, Burger P, Mazzucotelli T, Strehle A, Kummeling J, Collot N, et al. GenIDA, a participatory patient registry for genetic forms of intellectual disability provides detailed caregiver-reported information on 237 individuals with Koolen-de Vries syndrome. Genet Med Open. 2023;1:100817.","DOI":"10.1016\/j.gimo.2023.100817"},{"key":"10727","unstructured":"Koolen DA, Morgan A, de Vries BBA. Koolen-de Vries syndrome. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A. GeneReviews. Seattle: University of Washington; 2023."},{"key":"10728","doi-asserted-by":"crossref","unstructured":"Koolen DA, Pfundt R, Linda K, Beunders G, Veenstra-Knol HE, Conta JH, et al. The Koolen-de Vries syndrome: a phenotypic comparison of patients with a 17q21.31 microdeletion versus a KANSL1 sequence variant. Eur J Hum Genet. 2016;24:652-9.","DOI":"10.1038\/ejhg.2015.178"},{"key":"10729","doi-asserted-by":"crossref","unstructured":"Myers KA, Mandelstam SA, Ramantani G, Rushing EJ, de Vries BB, Koolen DA. The epileptology of Koolen-de Vries syndrome: electro-clinico-radiologic findings in 31 patients. Epilepsia. 2017;58:1085-94.","DOI":"10.1111\/epi.13746"},{"key":"10730","doi-asserted-by":"crossref","unstructured":"Karamik G, Tuysuz B, Isik E, Yilmaz A, Alanay Y, Sunamak EC, et al. The clinical phenotype of Koolen-de Vries syndrome in Turkish patients and literature review. Am J Med Genet A. 2023;191:1814-25.","DOI":"10.1002\/ajmg.a.63207"},{"key":"10731","doi-asserted-by":"crossref","unstructured":"El Chehadeh-Djebbar S, Callier P, Masurel-Paulet A, Bensignor C, M\u00e9jean N, Payet M, et al. 17q21.31 microdeletion in a patient with pituitary stalk interruption syndrome. Eur J Med Genet. 2011;54:369-73.","DOI":"10.1016\/j.ejmg.2011.03.001"},{"key":"10732","doi-asserted-by":"crossref","unstructured":"Ahmadov GA, Govender D, Atkinson MA, Sultanova RA, Eubova AA, Wasserfall CH, et al. Epidemiology of childhood-onset type 1 diabetes in Azerbaijan: Incidence, clinical features, biochemistry, and HLA-DRB1 status. Diabetes Res Clin Pract. 2018;144:252-9.","DOI":"10.1016\/j.diabres.2018.09.009"},{"key":"10733","doi-asserted-by":"crossref","unstructured":"Fejzo MS, Chen HW, Anderson L, McDermott MS, Karlan B, Konecny GE, et al. Analysis in epithelial ovarian cancer identifies KANSL1 as a biomarker and target gene for immune response and HDAC inhibition. Gynecol Oncol. 2021;160:539-46.","DOI":"10.1016\/j.ygyno.2020.11.008"},{"key":"10734","doi-asserted-by":"crossref","unstructured":"Lobo Y, Wheller L. Vitiligo in a 9-year-old girl with Koolen-de Vries syndrome. Dermatol Online J. 2021;27:13030\/qt05c1k2tc.","DOI":"10.5070\/D3274053171"},{"key":"10735","doi-asserted-by":"crossref","unstructured":"Maley AM, Spraker MK, de Vries BB, Koolen DA. Vitiligo in the Koolen-de Vries or 17q21.31 microdeletion syndrome. Clin Dysmorphol. 2015;24:86-7.","DOI":"10.1097\/MCD.0000000000000073"}],"container-title":["Acta M\u00e9dica Portuguesa"],"original-title":[],"link":[{"URL":"https:\/\/actamedicaportuguesa.com\/revista\/index.php\/amp\/article\/download\/22709\/15784","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/actamedicaportuguesa.com\/revista\/index.php\/amp\/article\/download\/22709\/15784","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T15:53:36Z","timestamp":1760543616000},"score":1,"resource":{"primary":{"URL":"https:\/\/actamedicaportuguesa.com\/revista\/index.php\/amp\/article\/view\/22709"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,15]]},"references-count":11,"URL":"https:\/\/doi.org\/10.20344\/amp.22709","relation":{},"ISSN":["1646-0758","0870-399X"],"issn-type":[{"value":"1646-0758","type":"electronic"},{"value":"0870-399X","type":"print"}],"subject":[],"published":{"date-parts":[[2025,10,15]]}}}