{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T21:09:27Z","timestamp":1781557767058,"version":"3.54.5"},"reference-count":22,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,17]],"date-time":"2024-11-17T00:00:00Z","timestamp":1731801600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health","award":["Ricerca Corrente 2023"],"award-info":[{"award-number":["Ricerca Corrente 2023"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background: Monoallelic damaging variants in PHIP (MIM*612870), encoding the Pleckstrin Homology Domain Interacting Protein, have been associated with a novel neurodevelopmental disorder, also termed Chung\u2013Jansen syndrome (CHUJANS, MIM#617991). Most of the described individuals show developmental delay (DD)\/intellectual disability (ID), obesity\/overweight, and variable congenital anomalies, so the condition can be considered as an ID\u2013overweight syndrome. Case Description: We evaluated a child presenting with DD\/ID and a craniofacial phenotype reminiscent of a Pitt\u2013Hopkins syndrome (PTHS)-like condition. We performed a clinical exome analysis on his biological sample, as well as an in silico prediction of the obtained data. At the same time, we interrogated the DeepGestalt technology powered by Face2Gene (F2G), using a frontal image of the proband, and clinically reviewed the earlier CHUJANS patients. In this child, we found a novel PHIP pathogenetic variant, which we corroborated through a protein modeling approach. The F2G platform supported the initial clinical hypothesis of a PTHS-like condition, while the clinical review highlighted the lack of the main frequent CHUJANS clinical features in this child. Conclusions: The unusual clinical presentation of this novel patient resembles a PTHS-like condition. However, a novel variant in PHIP has been unexpectedly detected, expanding the phenotypic spectrum of CHUJANS. Notably, PTHS (MIM#610954), which is a different ID syndrome caused by heterozygous variants in TCF4 (MIM*610954), is not classically considered in the differential diagnosis of CHUJANS nor has been cited in the previous studies. This could support other complex diagnoses and invite further patients\u2019 descriptions.<\/jats:p>","DOI":"10.3390\/children11111395","type":"journal-article","created":{"date-parts":[[2024,11,18]],"date-time":"2024-11-18T05:36:45Z","timestamp":1731908205000},"page":"1395","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Broadening the PHIP-Associated Neurodevelopmental Phenotype"],"prefix":"10.3390","volume":"11","author":[{"given":"Giulia","family":"Pascolini","sequence":"first","affiliation":[{"name":"Genetic Counselling Unit, Istituto Dermopatico dell\u2019Immacolata, IDI-IRCCS, Via dei Monti di Creta 104, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5622-7843","authenticated-orcid":false,"given":"Giovanni Luca","family":"Scaglione","sequence":"additional","affiliation":[{"name":"Bioinformatic Unit, Istituto Dermopatico dell\u2019Immacolata, IDI-IRCCS, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Balasubramanian","family":"Chandramouli","sequence":"additional","affiliation":[{"name":"Super Computing Applications and Innovation, Department High Performance Computing (HPC), CINECA, 40033 Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3501-6742","authenticated-orcid":false,"given":"Daniele","family":"Castiglia","sequence":"additional","affiliation":[{"name":"Molecular and Cell Biology Laboratory, Istituto Dermopatico dell\u2019Immacolata, IDI-IRCCS, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6106-599X","authenticated-orcid":false,"given":"Giovanni","family":"Di Zenzo","sequence":"additional","affiliation":[{"name":"Molecular and Cell Biology Laboratory, Istituto Dermopatico dell\u2019Immacolata, IDI-IRCCS, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biagio","family":"Didona","sequence":"additional","affiliation":[{"name":"Rare Diseases Center, Istituto Dermopatico dell\u2019Immacolata, IDI-IRCCS, 00167 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,17]]},"reference":[{"key":"ref_1","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. 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