{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:03:23Z","timestamp":1785420203468,"version":"3.56.0"},"reference-count":17,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T00:00:00Z","timestamp":1781308800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100007109","name":"University of Ferrara","doi-asserted-by":"crossref","award":["FAR2025"],"award-info":[{"award-number":["FAR2025"]}],"id":[{"id":"10.13039\/501100007109","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100007109","name":"University of Ferrara","doi-asserted-by":"crossref","award":["FAR2026"],"award-info":[{"award-number":["FAR2026"]}],"id":[{"id":"10.13039\/501100007109","id-type":"DOI","asserted-by":"crossref"}]},{"award":["FAR2025"],"award-info":[{"award-number":["FAR2025"]}],"id":[{"id":"https:\/\/ror.org\/041zkgm14","id-type":"ROR","asserted-by":"publisher"}]},{"award":["FAR2026"],"award-info":[{"award-number":["FAR2026"]}],"id":[{"id":"https:\/\/ror.org\/041zkgm14","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: Chung\u2013Jansen syndrome (CHUJANS) is a rare autosomal dominant genetic condition caused by pathogenic variants in the PHIP gene, which encodes a protein involved in neurodevelopmental processes and IGF-1 signalling. The phenotype is characterised by variable degrees of intellectual disability, early-onset obesity or overweight, distinctive facial dysmorphisms, and behavioural disturbances. We here present a case of Chung\u2013Jansen syndrome with a detailed endocrine work-up, highlighting the metabolic component of this syndrome. Case Presentation: We describe the case of a 21-year-old woman referred to our centre for evaluation of oligomenorrhea in the context of severe obesity (BMI 50.4 kg\/m2), short stature (151 cm, &lt;3rd percentile), and moderate-to-severe intellectual disability (full-scale IQ 38). Physical examination revealed dysmorphic features, including a round face, upslanting palpebral fissures, prominent zygomatic bones, anteverted nares, a prominent chin, and bilateral brachydactyly type E1. Laboratory investigations documented subclinical primary hypothyroidism of autoimmune origin, impaired glucose tolerance with associated hyperinsulinism, and polyendocrine metabolic ovarian syndrome (PMOS, previously known as PCOS). Exome analysis by next-generation sequencing (NGS) identified a heterozygous c.328C&gt;T [p.(Arg110Cys)] variant in the PHIP gene, already reported in literature and classified as likely pathogenic (ACMG class 4). Segregation analysis in the mother (father was not available for the test) did not reveal the variant, suggesting a de novo origin in the patient. Concurrently, the same analysis revealed a variant of uncertain significance in the ANKRD17 gene, while array-CGH detected a maternally inherited microdeletion of uncertain significance on chromosome X (Xp11.23). Conclusions: This case confirms the association between the PHIP p.(Arg110Cys) variant and the phenotype of Chung\u2013Jansen syndrome, providing a detailed characterisation of the endocrine and psychiatric comorbidities. Indeed, our report expands the knowledge on the endocrine phenotype providing further suggestion for personalised patient management. It underscores the importance of NGS in the diagnostic workup of syndromic obesity with intellectual disability, especially in the presence of negative family history and prior inconclusive genetic testing. This case suggests the inclusion of comprehensive endocrine evaluations in future studies on patients with Chung\u2013Jansen syndrome, in order to support endocrine work-up and facilitate early identification and appropriate management of potentially treatable alterations.<\/jats:p>","DOI":"10.3390\/jcm15124609","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T08:57:58Z","timestamp":1781513878000},"page":"4609","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Chung\u2013Jansen Syndrome in a Young Woman with a PHIP Variant: Severe Obesity, Intellectual Disability, and Endocrine Abnormalities"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6021-421X","authenticated-orcid":false,"given":"Francesco","family":"Donno","sequence":"first","affiliation":[{"name":"Section of Endocrinology, Geriatrics and Internal Medicine, Department of Medical Sciences, University of Ferrara, 44124 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-6353-0625","authenticated-orcid":false,"given":"Federica","family":"Bianco","sequence":"additional","affiliation":[{"name":"Section of Endocrinology, Geriatrics and Internal Medicine, Department of Medical Sciences, University of Ferrara, 44124 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Schinin\u00e0","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Department of Medical Science and Department of Mother and Child, Ferrara University and Ferrara University Hospital, 44124 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3099-0100","authenticated-orcid":false,"given":"Rita","family":"Selvatici","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Department of Medical Science and Department of Mother and Child, Ferrara University and Ferrara University Hospital, 44124 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppina","family":"Stoico","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Department of Medical Science and Department of Mother and Child, Ferrara University and Ferrara University Hospital, 44124 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8385-9870","authenticated-orcid":false,"given":"Alessandra","family":"Ferlini","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Department of Medical Science and Department of Mother and Child, Ferrara University and Ferrara University Hospital, 44124 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4010-2154","authenticated-orcid":false,"given":"Alberto","family":"Gobbo","sequence":"additional","affiliation":[{"name":"Section of Endocrinology, Geriatrics and Internal Medicine, Department of Medical Sciences, University of Ferrara, 44124 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8408-7796","authenticated-orcid":false,"given":"Maria Chiara","family":"Zatelli","sequence":"additional","affiliation":[{"name":"Section of Endocrinology, Geriatrics and Internal Medicine, Department of Medical Sciences, University of Ferrara, 44124 Ferrara, Italy"},{"name":"Endocrine Unit, University Hospital S. Anna, 44124 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0336-7097","authenticated-orcid":false,"given":"Stefania","family":"Bigoni","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit, Department of Medical Science and Department of Mother and Child, Ferrara University and Ferrara University Hospital, 44124 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7911-9770","authenticated-orcid":false,"given":"Maria Rosaria","family":"Ambrosio","sequence":"additional","affiliation":[{"name":"Section of Endocrinology, Geriatrics and Internal Medicine, Department of Medical Sciences, University of Ferrara, 44124 Ferrara, Italy"},{"name":"Endocrine Unit, University Hospital S. Anna, 44124 Ferrara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"a001172","DOI":"10.1101\/mcs.a001172","article-title":"De novo PHIP-predicted deleterious variants are associated with developmental delay, intellectual disability, obesity, and dysmorphic features","volume":"2","author":"Webster","year":"2016","journal-title":"Cold Spring Harb. Mol. Case Stud."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1038\/s41431-017-0039-5","article-title":"A genotype-first approach identifies an intellectual disability-overweight syndrome caused by PHIP haploinsufficiency","volume":"26","author":"Jansen","year":"2018","journal-title":"Eur. J. Hum. 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