{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T05:16:11Z","timestamp":1737695771829,"version":"3.33.0"},"reference-count":33,"publisher":"Walter de Gruyter GmbH","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_jpem-2024-0494_abs_001\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Moebius syndrome (MS) is a rare congenital non-progressive rhombencephalic disorder mostly characterised by abducens and facial nerve palsy, but with a multifaceted clinical presentation. Isolated or multiple pituitary hormone deficiencies in the setting of MS have been occasionally reported, but the simultaneous involvement of three or more hypothalamic-pituitary axes has never been described. We hereby report the case of a girl with MS that showed a co-occurrence of GH-, TSH- and ACTH-deficiency. In addition, we provide a systematic revision of all the published cases of hypopituitarism among patients with MS.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2024-0494_abs_002\">\n                  <jats:title>Case presentation<\/jats:title>\n                  <jats:p>A 6-year-old patient with a MS was referred to our outpatient clinic for faltering growth. The combination of stature below\u00a0\u22123.0 SDS, impaired height velocity and pathological response to two GH-stimulation tests prompted the diagnosis of GH deficiency and therefore recombinant human GH was undertaken. Brain MRI highlighted a thin infundibular stalk. By the age of 10 years, she started to complain progressive fatigue and the co-occurrence of remarkably decreased fT4 levels in the setting of non-increased TSH led to diagnose central hypothyroidism. Accordingly, she was started on levothyroxine replacement therapy with timely clinical improvement. At the age of 11.3 years, recurrent symptoms consistent with morning hypoglycaemia prompted the prescription of a low-dose ACTH test, that confirmed an ACTH deficiency, in the setting of a multiple pituitary hormonal impairment.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_jpem-2024-0494_abs_003\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Patients with MS are potentially at risk for either isolated or multiple pituitary hormones deficiency. Clinicians should lower the threshold for prescribing a dedicated endocrine assessment.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/jpem-2024-0494","type":"journal-article","created":{"date-parts":[[2025,1,23]],"date-time":"2025-01-23T09:52:56Z","timestamp":1737625976000},"source":"Crossref","is-referenced-by-count":0,"title":["Moebius syndrome and hypopituitarism: a case of multiple pituitary hormone deficiency and revision of the literature"],"prefix":"10.1515","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2196-5106","authenticated-orcid":false,"given":"Silvia","family":"Molinari","sequence":"first","affiliation":[{"name":"Pediatrics , Fondazione IRCCS San Gerardo Dei Tintori , Monza , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Laura","family":"Nicolosi","sequence":"additional","affiliation":[{"name":"Pediatrics , Fondazione IRCCS San Gerardo Dei Tintori , Monza , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"Selicorni","sequence":"additional","affiliation":[{"name":"Pediatrics , ASST Lariana Sant\u2019Anna Hospital , Como , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chiara","family":"Fossati","sequence":"additional","affiliation":[{"name":"Pediatrics , Fondazione IRCCS San Gerardo Dei Tintori , Monza , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martina","family":"Lattuada","sequence":"additional","affiliation":[{"name":"Pediatrics , Fondazione IRCCS San Gerardo Dei Tintori , Monza , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iacopo","family":"Bellani","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery , University of Milano-Bicocca , Milano , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Arcuti","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery , University of Milano-Bicocca , Milano , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riccardo","family":"Carnevale","sequence":"additional","affiliation":[{"name":"School of Medicine and Surgery , University of Milano-Bicocca , Milano , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea","family":"Biondi","sequence":"additional","affiliation":[{"name":"Pediatrics , Fondazione IRCCS San Gerardo Dei Tintori , Monza , Italy"},{"name":"School of Medicine and Surgery , University of Milano-Bicocca , Milano , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adriana","family":"Balduzzi","sequence":"additional","affiliation":[{"name":"Pediatrics , Fondazione IRCCS San Gerardo Dei Tintori , Monza , Italy"},{"name":"School of Medicine and Surgery , University of Milano-Bicocca , Milano , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Cattoni","sequence":"additional","affiliation":[{"name":"Pediatrics , Fondazione IRCCS San Gerardo Dei Tintori , Monza , Italy"},{"name":"School of Medicine and Surgery , University of Milano-Bicocca , Milano , Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2025,1,24]]},"reference":[{"key":"2025012309554389919_j_jpem-2024-0494_ref_001","doi-asserted-by":"crossref","unstructured":"Carta, A, Favilla, S, Calzetti, G, Casalini, MC, Ferrari, PF, Bianchi, B, et al.. The epidemiology of Moebius syndrome in Italy. Orphanet J Rare Dis 2021;16:162. https:\/\/doi.org\/10.1186\/s13023-021-01808-2. [Internet] Available from: https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-021-01808-2.","DOI":"10.1186\/s13023-021-01808-2"},{"key":"2025012309554389919_j_jpem-2024-0494_ref_002","doi-asserted-by":"crossref","unstructured":"Picciolini, O, Porro, M, Cattaneo, E, Castelletti, S, Masera, G, Mosca, F, et al.. Moebius syndrome: clinical features, diagnosis, management and early intervention. Ital J Pediatr 2016;42:56. https:\/\/doi.org\/10.1186\/s13052-016-0256-5. [Internet] Available from: http:\/\/ijponline.biomedcentral.com\/articles\/10.1186\/s13052-016-0256-5.","DOI":"10.1186\/s13052-016-0256-5"},{"key":"2025012309554389919_j_jpem-2024-0494_ref_003","doi-asserted-by":"crossref","unstructured":"Verzijl, HTFM, Van der Zwaag, B, Cruysberg, JRM, Padberg, GW. M\u00f6bius syndrome redefined: a syndrome of rhombencephalic maldevelopment. 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J Endocrinol Metab 2016;4:44\u20138."},{"key":"2025012309554389919_j_jpem-2024-0494_ref_016","doi-asserted-by":"crossref","unstructured":"Chora\u0327zy, M, Le\u015bniewicz, R, Posmyk, R, Halicka, D, Zalewska, A, Wincewicz-Pietrzykowska, A, et al.. The natural history of M\u00f6bius syndrome in a 32-year-old man. Neurol Neurochir Pol 2011;45:74\u20139. https:\/\/doi.org\/10.1016\/s0028-3843(14)60063-3.","DOI":"10.1016\/S0028-3843(14)60063-3"},{"key":"2025012309554389919_j_jpem-2024-0494_ref_017","doi-asserted-by":"crossref","unstructured":"McCabe, MJ, Gaston-Massuet, C, Tziaferi, V, Gregory, LC, Alatzoglou, KS, Signore, M, et al.. Novel FGF8 mutations associated with recessive holoprosencephaly, craniofacial defects, and hypothalamo-pituitary dysfunction. J Clin Endocrinol Metab 2011;96:E1709\u201318. https:\/\/doi.org\/10.1210\/jc.2011-0454. 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Frequency of genetic defects in combined pituitary hormone deficiency: a systematic review and analysis of a multicentre Italian cohort. Clin Endocrinol (Oxf) 2015;83:849\u201360. https:\/\/doi.org\/10.1111\/cen.12849.","DOI":"10.1111\/cen.12849"},{"key":"2025012309554389919_j_jpem-2024-0494_ref_027","doi-asserted-by":"crossref","unstructured":"Crisafulli, G, Aversa, T, Zirilli, G, De Luca, F, Gallizzi, R, Wasniewska, M. Congenital hypopituitarism: how to select the patients for genetic analyses. Ital J Pediatr 2018;44:1\u20134. https:\/\/doi.org\/10.1186\/s13052-018-0484-y.","DOI":"10.1186\/s13052-018-0484-y"},{"key":"2025012309554389919_j_jpem-2024-0494_ref_028","doi-asserted-by":"crossref","unstructured":"Giordano, M. Genetic causes of isolated and combined pituitary hormone deficiency. Best Pract Res Clin Endocrinol Metab 2016;30:679\u201391. [Internet] Available from: https:\/\/doi.org\/10.1016\/j.beem.2016.09.005.","DOI":"10.1016\/j.beem.2016.09.005"},{"key":"2025012309554389919_j_jpem-2024-0494_ref_029","doi-asserted-by":"crossref","unstructured":"Parkin, K, Kapoor, R, Bhat, R, Greenough, A. Genetic causes of hypopituitarism. Arch Med Sci 2020;16:27\u201333. https:\/\/doi.org\/10.5114\/aoms.2020.91285. [Internet] Available from: https:\/\/www.termedia.pl\/doi\/10.5114\/aoms.2020.91285.","DOI":"10.5114\/aoms.2020.91285"},{"key":"2025012309554389919_j_jpem-2024-0494_ref_030","unstructured":"Emmanuel, M, Bokor, BR. Tanner stages. StatPearls 2021. [Internet] Available from: http:\/\/www.ncbi.nlm.nih.gov\/pubmed\/29262142."},{"key":"2025012309554389919_j_jpem-2024-0494_ref_031","unstructured":"Moebius syndrome-axonal neuropathy-hypogonadotropic hypogonadism syndrome, ORPHA:2560 [Internet]. Available from: https:\/\/www.orpha.net\/en\/disease\/detail\/2560."},{"key":"2025012309554389919_j_jpem-2024-0494_ref_032","doi-asserted-by":"crossref","unstructured":"Chew, S, Balasubramanian, R, Chan, WM, Kang, PB, Andrews, C, Webb, BD, et al.. A novel syndrome caused by the E410K amino acid substitution in the neuronal \u03b2-tubulin isotype 3. Brain 2013;136:522\u201335. https:\/\/doi.org\/10.1093\/brain\/aws345.","DOI":"10.1093\/brain\/aws345"},{"key":"2025012309554389919_j_jpem-2024-0494_ref_033","doi-asserted-by":"crossref","unstructured":"Xatzipsalti, M, Voutetakis, A, Stamoyannou, L, Chrousos, G, Kanaka-Gantenbein, C. Congenital hypopituitarism: various genes, various phenotypes. Horm Metab Res 2019;51:81\u201390. https:\/\/doi.org\/10.1055\/a-0822-3637. 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