{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T04:00:35Z","timestamp":1790308835195,"version":"4.1.0"},"reference-count":71,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Neuroendocrinology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    To describe clinical presentation and genetic findings in a cohort of infants with congenital hypogonadotropic hypogonadism (CHH) diagnosed before 2\u2009years of age. From a large cohort of patients who underwent next\u2010generation sequencing (NGS) for CHH between 2019 and 2025, we identified all patients tested at \u22642\u2009years of age. Genetic analysis consisted of a targeted CHH gene panel, followed by a CPHD\u2010NGS panel. In one remaining patient with neurodevelopmental defects, whole\u2010exome sequencing was performed. Phenotypic data were collected through the GENHYPOPIT registry. Twelve male infants (1.5% of the total cohort) met the inclusion criteria; one additional patient via familial screening was included, for a total of 13 patients. All had micropenis; four had associated cryptorchidism (bilateral in half of cases). CHH was biologically confirmed during mini\u2010puberty in 10 infants, at a median age of 6.8\u2009weeks. Seven of these 10 infants received gonadotropin therapy, at an average of 4.1\u2009months. MRI revealed bilateral olfactory bulb agenesis in five cases. A pathogenic or likely pathogenic variant was identified in 7 of 12 patients (58%), involving\n                    <jats:italic>TACR3<\/jats:italic>\n                    (\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u20092),\n                    <jats:italic>ANOS1<\/jats:italic>\n                    ,\n                    <jats:italic>FGFR1<\/jats:italic>\n                    (including two novel variants),\n                    <jats:italic>SOX10<\/jats:italic>\n                    ,\n                    <jats:italic>GLI2<\/jats:italic>\n                    (through the CPHD panel), and\n                    <jats:italic>SOX11<\/jats:italic>\n                    (identified by exome sequencing). A genetic cause was identified in 58% of cases, a diagnostic yield higher than reported in pubertal cohorts. Early genetic diagnosis allowed anticipatory monitoring for syndromic manifestations and associated pituitary deficiencies\u2014particularly relevant for\n                    <jats:italic>FGFR1<\/jats:italic>\n                    and\n                    <jats:italic>GLI2<\/jats:italic>\n                    variant carriers at risk of CPHD. Our findings support the inclusion of\n                    <jats:italic>GLI2<\/jats:italic>\n                    and\n                    <jats:italic>SOX11<\/jats:italic>\n                    in targeted HH gene panels.\n                  <\/jats:p>","DOI":"10.1111\/jne.70274","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T03:28:18Z","timestamp":1790306898000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetic landscape of a neonatal hypogonadotropic hypogonadism series: Novel variants and phenotypic spectrum"],"prefix":"10.1111","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5550-9636","authenticated-orcid":false,"given":"Karine","family":"Aouchiche","sequence":"first","affiliation":[{"name":"Assistance Publique\u2010H\u00f4pitaux de Marseille (APHM), Department of Paediatrics, Paediatric Endocrinology Unit CHU Timone Enfants  Marseille France"},{"name":"Multidisciplinary Pediatric Department Aix Marseille Univ, APHM, INSERM, MMG, UMR 1251, La Timone Children's Hospital  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Van Wormhoudt","sequence":"additional","affiliation":[{"name":"Assistance Publique\u2010H\u00f4pitaux de Marseille (APHM), Department of Paediatrics, Paediatric Endocrinology Unit CHU Timone Enfants  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6527-805X","authenticated-orcid":false,"given":"Kevin","family":"Perge","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon (HCL), Pediatric endocrinology Unit, H\u00f4pital Femme M\u00e8re Enfant Universit\u00e9 Claude Bernard Lyon 1  Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Dornberger","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Genetic, and Gynecology University Hospital of Toulouse Children's Hospital  Toulouse France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Colson","sequence":"additional","affiliation":[{"name":"Department of Genetics University Hospital of Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marine","family":"Delagrange","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Endocrinology and Diabetology University Hospital of Bordeaux  Bordeaux France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Leroy","sequence":"additional","affiliation":[{"name":"Department of Pediatric Endocrinology, Diabetology Metabolism University Hospital of Lille  Lille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Ledmazel","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Annecy Genevois Hospital  Epagny Metz\u2010Tessy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7618-8965","authenticated-orcid":false,"given":"Vanessa","family":"Menut","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Endocrinology and Diabetology University Hospital of Nantes  Nantes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica Benarrous","family":"Jaillet","sequence":"additional","affiliation":[{"name":"Hospices Civils de Lyon (HCL), Pediatric Genetic Unit, H\u00f4pital Femme M\u00e8re Enfant Universit\u00e9 Claude Bernard Lyon 1  Lyon France France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Djamel","family":"Bendifallah","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Alpes Leman Hospital Center  Contamine\u2010sur\u2010Arve France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamad Hage","family":"Chehade","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Boulogne sur Mer Hospital Center  Boulogne sur Mer France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christelle","family":"Dib","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Elbeuf\u2010Louviers\u2010Val de Reuil Intercommunal Hospital Center  Normandy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3740-6173","authenticated-orcid":false,"given":"Anne","family":"Barlier","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology GEnOP\u00e9 Aix Marseille Univ, APHM, INSERM, MMG, UMR 1251, La Timone University Hospital  Marseille France"},{"name":"Department of Endocrinology Aix Marseille Univ, APHM, INSERM, MMG, MarMaRa Institute, UMR 1251, La Conception University Hospital  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8482-6691","authenticated-orcid":false,"given":"Thierry","family":"Brue","sequence":"additional","affiliation":[{"name":"Department of Endocrinology Aix Marseille Univ, APHM, INSERM, MMG, MarMaRa Institute, UMR 1251, La Conception University Hospital  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5174-7049","authenticated-orcid":false,"given":"Rachel","family":"Reynaud","sequence":"additional","affiliation":[{"name":"Assistance Publique\u2010H\u00f4pitaux de Marseille (APHM), Department of Paediatrics, Paediatric Endocrinology Unit CHU Timone Enfants  Marseille France"},{"name":"Multidisciplinary Pediatric Department Aix Marseille Univ, APHM, INSERM, MMG, UMR 1251, La Timone Children's Hospital  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6365-1538","authenticated-orcid":false,"given":"Alexandru","family":"Saveanu","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular Biology GEnOP\u00e9 Aix Marseille Univ, APHM, INSERM, MMG, UMR 1251, La Timone University Hospital  Marseille France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"issue":"4","key":"e_1_2_12_2_1","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1038\/s41431-022-01261-0","article-title":"Panel testing for the molecular genetic diagnosis of congenital hypogonadotropic hypogonadism\u2014a clinical perspective","volume":"31","author":"Al Sayed Y","year":"2023","journal-title":"Eur J Hum Genet Avr"},{"key":"e_1_2_12_3_1","doi-asserted-by":"crossref","first-page":"S33","DOI":"10.1016\/S0003-4266(10)70005-6","article-title":"Hypogonadisme 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consequences, and potential for therapeutic replacement","volume":"45","author":"Rohayem J","year":"2024","journal-title":"Endocr Rev"},{"issue":"2","key":"e_1_2_12_7_1","first-page":"188","article-title":"Congenital hypogonadotropic hypogonadism: implications of absent mini\u2010puberty","volume":"41","author":"Dwyer AA","year":"2016","journal-title":"Minerva Endocrinol"},{"issue":"4","key":"e_1_2_12_8_1","doi-asserted-by":"crossref","first-page":"e921","DOI":"10.1210\/clinem\/dgae874","article-title":"Gonadotropin therapy for mini\u2010puberty induction in male infants with hypogonadotropic hypogonadism","volume":"110","author":"Rhys\u2010Evans S","year":"2025","journal-title":"J Clin Endocrinol Metab"},{"issue":"4","key":"e_1_2_12_9_1","doi-asserted-by":"crossref","DOI":"10.1530\/EC-22-0252","article-title":"Gonadotropin administration to mimic mini\u2010puberty in hypogonadotropic males: pump or injections?","volume":"12","author":"Avril T","year":"2023","journal-title":"Endocr 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