{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T18:53:14Z","timestamp":1789930394549,"version":"4.0.1"},"reference-count":186,"publisher":"The Endocrine Society","issue":"6","license":[{"start":{"date-parts":[[2019,11,8]],"date-time":"2019-11-08T00:00:00Z","timestamp":1573171200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Context<\/jats:title>\n                    <jats:p>Congenital hypopituitarism (CH) is characterized by the presence of deficiencies in one or more of the 6 anterior pituitary (AP) hormones secreted from the 5 different specialized cell types of the AP. During human embryogenesis, hypothalamo\u2013pituitary (HP) development is controlled by a complex spatio-temporal genetic cascade of transcription factors and signaling molecules within the hypothalamus and Rathke\u2019s pouch, the primordium of the AP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Evidence Acquisition<\/jats:title>\n                    <jats:p>This mini-review discusses the genes and pathways involved in HP development and how mutations of these give rise to CH. This may present in the neonatal period or later on in childhood and may be associated with craniofacial midline structural abnormalities such as cleft lip\/palate, visual impairment due to eye abnormalities such as optic nerve hypoplasia (ONH) and microphthalmia or anophthalmia, or midline forebrain neuroradiological defects including agenesis of the septum pellucidum or corpus callosum or the more severe holoprosencephaly.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Evidence Synthesis<\/jats:title>\n                    <jats:p>Mutations give rise to an array of highly variable disorders ranging in severity. There are many known causative genes in HP developmental pathways that are routinely screened in CH patients; however, over the last 5 years this list has rapidly increased due to the identification of variants in new genes and pathways of interest by next-generation sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The majority of patients with these disorders do not have an identified molecular basis, often making management challenging. This mini-review aims to guide clinicians in making a genetic diagnosis based on patient phenotype, which in turn may impact on clinical management.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1210\/clinem\/dgz184","type":"journal-article","created":{"date-parts":[[2019,11,8]],"date-time":"2019-11-08T12:29:57Z","timestamp":1573216197000},"page":"e2103-e2120","source":"Crossref","is-referenced-by-count":75,"title":["The Molecular Basis of Congenital Hypopituitarism and Related Disorders"],"prefix":"10.1210","volume":"105","author":[{"given":"Louise Cheryl","family":"Gregory","sequence":"first","affiliation":[{"name":"Genetics and Genomic Medicine Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0365-5809","authenticated-orcid":false,"given":"Mehul Tulsidas","family":"Dattani","sequence":"additional","affiliation":[{"name":"Genetics and Genomic Medicine Research and Teaching Department, UCL Great Ormond Street Institute of Child Health, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2019,11,8]]},"reference":[{"issue":"1","key":"2021122105215639600_CIT0001","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1097\/MED.0b013e32834ed639","article-title":"Genetic disorders of the pituitary","volume":"19","author":"Cohen","year":"2012","journal-title":"Curr Opin Endocrinol Diabetes Obes."},{"key":"2021122105215639600_CIT0002","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1159\/000341733","article-title":"Pituitary gland development: an update","volume":"23","author":"Bancalari","year":"2012","journal-title":"Endocr Dev."},{"issue":"7","key":"2021122105215639600_CIT0003","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1210\/er.2009-0008","article-title":"Genetic regulation of pituitary gland development in human and mouse","volume":"30","author":"Kelberman","year":"2009","journal-title":"Endocr Rev."},{"issue":"11","key":"2021122105215639600_CIT0004","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1016\/j.earlhumdev.2009.08.057","article-title":"Genetic forms of hypopituitarism and their manifestation in the neonatal period","volume":"85","author":"Alatzoglou","year":"2009","journal-title":"Early Hum Dev."},{"issue":"7","key":"2021122105215639600_CIT0005","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1038\/gim.2017.165","article-title":"Identification of SLC20A1 and SLC15A4 among other genes as potential risk factors for combined pituitary hormone deficiency","volume":"20","author":"Simm","year":"2018","journal-title":"Genet Med."},{"key":"2021122105215639600_CIT0006","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1016\/j.ebiom.2018.09.026","article-title":"Screening a large pediatric cohort with GH deficiency for mutations in genes regulating pituitary development and GH secretion: frequencies, phenotypes and growth outcomes","volume":"36","author":"Blum","year":"2018","journal-title":"Ebiomedicine."},{"issue":"3","key":"2021122105215639600_CIT0007","doi-asserted-by":"crossref","first-page":"376","DOI":"10.1111\/j.1365-2265.2009.03572.x","article-title":"Congenital hypopituitarism: clinical, molecular and neuroradiological correlates","volume":"71","author":"Mehta","year":"2009","journal-title":"Clin Endocrinol (Oxf)."},{"issue":"1-2","key":"2021122105215639600_CIT0008","first-page":"267","article-title":"[Studies on malformation of cranio-encephalic sutures. III. Agenesis of the septum lucidum with malformation of the optic tract]","volume":"77","author":"DE MORSIER","year":"1956","journal-title":"Schweiz Arch Neurol Psychiatr."},{"issue":"1","key":"2021122105215639600_CIT0009","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1001\/archopht.1993.01090010070029","article-title":"Optic nerve hypoplasia. Clinical significance of associated central nervous system abnormalities on magnetic resonance imaging","volume":"111","author":"Brodsky","year":"1993","journal-title":"Arch Ophthalmol."},{"issue":"4","key":"2021122105215639600_CIT0010","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1007\/s11102-007-0055-5","article-title":"Genetics of septo-optic dysplasia","volume":"10","author":"Kelberman","year":"2007","journal-title":"Pituitary."},{"issue":"4","key":"2021122105215639600_CIT0011","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1038\/ejhg.2009.125","article-title":"Septo-optic dysplasia","volume":"18","author":"Webb","year":"2010","journal-title":"Eur J Hum Genet."},{"issue":"8133","key":"2021122105215639600_CIT0012","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/S0140-6736(79)90138-7","article-title":"Septo-optic dysplasia and maternal 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related activator is required for pituitary organogenesis","volume":"15","author":"Dasen","year":"2001","journal-title":"Genes Dev."},{"issue":"5","key":"2021122105215639600_CIT0022","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1002\/humu.9332","article-title":"Alu-element insertion in the homeodomain of HESX1 and aplasia of the anterior pituitary","volume":"25","author":"Sobrier","year":"2005","journal-title":"Hum Mutat."},{"key":"2021122105215639600_CIT0023","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1530\/EJE-07-0156","article-title":"Hypothalamic and pituitary development: novel insights into the aetiology","volume":"157 Suppl 1","author":"Kelberman","year":"2007","journal-title":"Eur J Endocrinol."},{"issue":"1","key":"2021122105215639600_CIT0024","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1210\/jc.2008-1219","article-title":"OTX2 loss of function mutation causes anophthalmia and combined pituitary hormone deficiency with a small anterior and ectopic posterior pituitary","volume":"94","author":"Tajima","year":"2009","journal-title":"J Clin Endocrinol Metab."},{"issue":"21","key":"2021122105215639600_CIT0025","doi-asserted-by":"crossref","first-page":"2646","DOI":"10.1101\/gad.9.21.2646","article-title":"Mouse Otx2 functions in the formation and patterning of rostral head","volume":"9","author":"Matsuo","year":"1995","journal-title":"Genes Dev."},{"issue":"4","key":"2021122105215639600_CIT0026","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1093\/hmg\/ddu506","article-title":"Deletion of OTX2 in neural ectoderm delays anterior pituitary development","volume":"24","author":"Mortensen","year":"2015","journal-title":"Hum Mol Genet."},{"issue":"3","key":"2021122105215639600_CIT0027","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1530\/EJE-12-0333","article-title":"A novel OTX2 mutation in a patient with combined pituitary hormone deficiency, pituitary malformation, and an underdeveloped left optic nerve","volume":"167","author":"Gorbenko Del Blanco","year":"2012","journal-title":"Eur J Endocrinol."},{"issue":"6","key":"2021122105215639600_CIT0028","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1086\/430721","article-title":"Heterozygous mutations of OTX2 cause severe ocular malformations","volume":"76","author":"Ragge","year":"2005","journal-title":"Am J Hum Genet."},{"issue":"11","key":"2021122105215639600_CIT0029","doi-asserted-by":"crossref","first-page":"E278","DOI":"10.1002\/humu.20869","article-title":"Novel heterozygous OTX2 mutations and whole gene deletions in anophthalmia, microphthalmia and coloboma","volume":"29","author":"Wyatt","year":"2008","journal-title":"Hum Mutat."},{"issue":"6633","key":"2021122105215639600_CIT0030","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1038\/42475","article-title":"The Rx homeobox gene is essential for vertebrate eye 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Genet."},{"issue":"1","key":"2021122105215639600_CIT0034","doi-asserted-by":"crossref","first-page":"9064","DOI":"10.1038\/s41598-017-09276-0","article-title":"Unraveling the genetic cause of a consanguineous family with unilateral coloboma and retinoschisis: expanding the phenotypic variability of RAX mutations","volume":"7","author":"Huang","year":"2017","journal-title":"Sci Rep."},{"issue":"7","key":"2021122105215639600_CIT0035","doi-asserted-by":"crossref","first-page":"2925","DOI":"10.1210\/jc.2018-02316","article-title":"Truncating RAX mutations: anophthalmia, hypopituitarism, diabetes insipidus, and cleft palate in mice and men","volume":"104","author":"Brachet","year":"2019","journal-title":"J Clin Endocrinol Metab."},{"issue":"9","key":"2021122105215639600_CIT0036","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1093\/hmg\/ddl064","article-title":"Mutations in SOX2 cause anophthalmia-esophageal-genital (AEG) syndrome","volume":"15","author":"Williamson","year":"2006","journal-title":"Hum Mol Genet."},{"issue":"4","key":"2021122105215639600_CIT0037","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1038\/ng1120","article-title":"Mutations in SOX2 cause anophthalmia","volume":"33","author":"Fantes","year":"2003","journal-title":"Nat Genet."},{"issue":"9","key":"2021122105215639600_CIT0038","first-page":"2442","article-title":"Mutations within Sox2\/SOX2 are associated with abnormalities in the hypothalamo-pituitary-gonadal axis in mice and humans","volume":"116","author":"Kelberman","year":"2006","journal-title":"J Clin Invest."},{"issue":"21","key":"2021122105215639600_CIT0039","doi-asserted-by":"crossref","first-page":"2794","DOI":"10.1002\/ajmg.a.32384","article-title":"Familial recurrence of SOX2 anophthalmia syndrome: phenotypically normal mother with two affected daughters","volume":"146A","author":"Schneider","year":"2008","journal-title":"Am J Med Genet A."},{"issue":"10","key":"2021122105215639600_CIT0040","doi-asserted-by":"crossref","first-page":"3635","DOI":"10.1172\/JCI64311","article-title":"SOX2 regulates the hypothalamic-pituitary axis at multiple levels","volume":"122","author":"Jayakody","year":"2012","journal-title":"J Clin Invest."},{"issue":"7","key":"2021122105215639600_CIT0041","doi-asserted-by":"crossref","first-page":"753","DOI":"10.1038\/ejhg.2011.11","article-title":"Isolated hypogonadotropic hypogonadism with SOX2 mutation and anophthalmia\/microphthalmia in offspring","volume":"19","author":"Stark","year":"2011","journal-title":"Eur J Hum Genet."},{"issue":"8","key":"2021122105215639600_CIT0042","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1507\/endocrj.EJ17-0078","article-title":"SOX2 nonsense mutation in a patient clinically diagnosed with non-syndromic hypogonadotropic hypogonadism","volume":"64","author":"Shima","year":"2017","journal-title":"Endocr J."},{"issue":"12","key":"2021122105215639600_CIT0043","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1002\/humu.21606","article-title":"SOX2 haploinsufficiency is associated with slow progressing hypothalamo-pituitary tumours","volume":"32","author":"Alatzoglou","year":"2011","journal-title":"Hum Mutat."},{"issue":"4","key":"2021122105215639600_CIT0044","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.stem.2013.07.004","article-title":"Sox2(+) stem\/progenitor cells in the adult mouse pituitary support organ homeostasis and have tumor-inducing potential","volume":"13","author":"Andoniadou","year":"2013","journal-title":"Cell Stem Cell."},{"issue":"13","key":"2021122105215639600_CIT0045","first-page":"2376","article-title":"SOX2 is sequentially required for progenitor proliferation and lineage specification in the developing pituitary","volume":"143","author":"Goldsmith","year":"2016","journal-title":"Development."},{"issue":"6","key":"2021122105215639600_CIT0046","doi-asserted-by":"crossref","first-page":"1450","DOI":"10.1086\/344661","article-title":"Transcription factor SOX3 is involved in X-linked mental retardation with growth hormone deficiency","volume":"71","author":"Laumonnier","year":"2002","journal-title":"Am J Hum Genet."},{"issue":"5","key":"2021122105215639600_CIT0047","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1086\/430134","article-title":"Over- and underdosage of SOX3 is associated with infundibular hypoplasia and hypopituitarism","volume":"76","author":"Woods","year":"2005","journal-title":"Am J Hum Genet."},{"issue":"1","key":"2021122105215639600_CIT0048","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/(SICI)1096-8628(19960712)64:1<35::AID-AJMG5>3.0.CO;2-Q","article-title":"Familial X-linked mental retardation and isolated growth hormone deficiency: clinical and molecular findings","volume":"64","author":"Hamel","year":"1996","journal-title":"Am J Med Genet."},{"issue":"12","key":"2021122105215639600_CIT0049","doi-asserted-by":"crossref","first-page":"E2702","DOI":"10.1210\/jc.2014-1160","article-title":"SOX3 deletion in mouse and human is associated with persistence of the craniopharyngeal canal","volume":"99","author":"Alatzoglou","year":"2014","journal-title":"J Clin Endocrinol Metab."},{"issue":"4","key":"2021122105215639600_CIT0050","doi-asserted-by":"crossref","first-page":"E685","DOI":"10.1210\/jc.2010-1239","article-title":"Increased transactivation associated with SOX3 polyalanine tract deletion in a patient with hypopituitarism","volume":"96","author":"Alatzoglou","year":"2011","journal-title":"J Clin Endocrinol Metab."},{"issue":"3","key":"2021122105215639600_CIT0051","doi-asserted-by":"crossref","first-page":"e1003290","DOI":"10.1371\/journal.pgen.1003290","article-title":"Mechanistic insight into the pathology of polyalanine expansion disorders revealed by a mouse model for X linked hypopituitarism","volume":"9","author":"Hughes","year":"2013","journal-title":"Plos Genet."},{"issue":"3","key":"2021122105215639600_CIT0052","doi-asserted-by":"crossref","first-page":"1062","DOI":"10.1210\/jc.2007-1525","article-title":"Three novel missense mutations within the LHX4 gene are associated with variable pituitary hormone deficiencies","volume":"93","author":"Pfaeffle","year":"2008","journal-title":"J Clin Endocrinol Metab."},{"issue":"7","key":"2021122105215639600_CIT0053","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1055\/s-0029-1225612","article-title":"A novel mutation (V101A) of the LHX4 gene in a Japanese patient with combined pituitary hormone deficiency","volume":"118","author":"Tajima","year":"2010","journal-title":"Exp Clin Endocrinol Diabetes."},{"issue":"9","key":"2021122105215639600_CIT0054","doi-asserted-by":"crossref","first-page":"e46008","DOI":"10.1371\/journal.pone.0046008","article-title":"Gradual loss of ACTH due to a novel mutation in LHX4: comprehensive mutation screening in Japanese patients with congenital hypopituitarism","volume":"7","author":"Takagi","year":"2012","journal-title":"Plos One."},{"issue":"6","key":"2021122105215639600_CIT0055","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1111\/cen.12849","article-title":"Frequency of genetic defects in combined pituitary hormone deficiency: a systematic review and analysis of a multicentre Italian cohort","volume":"83","author":"De Rienzo","year":"2015","journal-title":"Clin Endocrinol (Oxf)."},{"issue":"3","key":"2021122105215639600_CIT0056","first-page":"216","article-title":"[Transcription factors of the anterior pituitary and combined hypopituitarism]","volume":"60","author":"Vallette","year":"1999","journal-title":"Ann Endocrinol (Paris)."},{"issue":"5","key":"2021122105215639600_CIT0057","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1086\/323764","article-title":"Syndromic short stature in patients with a germline mutation in the LIM homeobox LHX4","volume":"69","author":"Machinis","year":"2001","journal-title":"Am J Hum Genet."},{"issue":"2","key":"2021122105215639600_CIT0058","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1297\/cpe.22.15","article-title":"Molecular and clinical findings in patients with LHX4 and OTX2 mutations","volume":"22","author":"Tajima","year":"2013","journal-title":"Clin Pediatr Endocrinol."},{"issue":"6","key":"2021122105215639600_CIT0059","doi-asserted-by":"crossref","first-page":"2158","DOI":"10.1210\/jc.2014-4484","article-title":"Novel lethal form of congenital hypopituitarism associated with the first recessive LHX4 mutation","volume":"100","author":"Gregory","year":"2015","journal-title":"J Clin Endocrinol Metab."},{"issue":"1","key":"2021122105215639600_CIT0060","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1210\/jc.2016-3158","article-title":"Contribution of LHX4 mutations to pituitary deficits in a Cohort of 417 unrelated patients","volume":"102","author":"Cohen","year":"2017","journal-title":"J Clin Endocrinol Metab."},{"issue":"2","key":"2021122105215639600_CIT0061","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1038\/76041","article-title":"Mutations in LHX3 result in a new syndrome revealed by combined pituitary hormone deficiency","volume":"25","author":"Netchine","year":"2000","journal-title":"Nat Genet."},{"issue":"3","key":"2021122105215639600_CIT0062","doi-asserted-by":"crossref","first-page":"E503","DOI":"10.1210\/jc.2011-2095","article-title":"Symptomatic heterozygotes and prenatal diagnoses in a nonconsanguineous family with syndromic combined pituitary hormone deficiency resulting from two novel LHX3 mutations","volume":"97","author":"Sobrier","year":"2012","journal-title":"J Clin Endocrinol Metab."},{"issue":"5","key":"2021122105215639600_CIT0063","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1007\/BF03345298","article-title":"Magnetic resonance imaging of the hypothalamus-pituitary unit in childrensuspected of hypopituitarism: who, how and when toinvestigate","volume":"27","author":"Maghnie","year":"2004","journal-title":"J Endocrinol Invest."},{"issue":"5264","key":"2021122105215639600_CIT0064","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1126\/science.272.5264.1004","article-title":"Specification of pituitary cell lineages by the LIM homeobox gene Lhx3","volume":"272","author":"Sheng","year":"1996","journal-title":"Science."},{"issue":"10","key":"2021122105215639600_CIT0065","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1210\/me.2015-1192","article-title":"ISL1 is necessary for maximal thyrotrope response to 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