{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T09:11:57Z","timestamp":1777972317894,"version":"3.51.4"},"reference-count":15,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T00:00:00Z","timestamp":1777939200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: DDX3X syndrome (MIM#300958) is a neurodevelopmental disorder associated with intellectual disability, language impairment, and a characteristic neurobehavioral phenotype that predominantly affects females. Although dysmorphic features have been reported, a consistent facial phenotype and clear genotype\u2013phenotype correlations have not been established. Methods: We conducted an observational, ambispective, descriptive study including patients aged 0\u201318 years with a molecular diagnosis of DDX3X. Clinical, standardized facial images, neurobehavioral, neuroimaging, and molecular data were collected. Automated facial analysis was performed using Face2Gene after algorithm training. Results: Of 11 identified patients, 9 were included (8 females); 8 variants were de novo and 4 novel. Two variants of uncertain significance underwent in silico analysis. Frequent facial features included thin upper lip (9\/9), tapered chin (8\/9), long uniform eyebrows (8\/9), short neck (8\/9), and long face (6\/9). After training, Face2Gene identified DDX3X syndrome in 92% of cases within the top 5 suggestions, supporting its utility as a diagnostic aid. All females had intellectual disability and language disorder; 66% presented sleep disturbances and aggressive behavior. Neuroimaging revealed ventricular dilatation (5\/9) and corpus callosum hypoplasia (3\/9). Loss-of-function variants were associated with greater clinical severity. Conclusions: This series suggests a recognizable facial phenotype of DDX3X syndrome and supports a possible genotype\u2013phenotype correlation. Further studies are needed to confirm these findings.<\/jats:p>","DOI":"10.3390\/genes17050551","type":"journal-article","created":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T07:57:29Z","timestamp":1777967849000},"page":"551","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["DDX3X Syndrome: Clinical, Neuroimaging, AI-Assisted Facial Profiling and Genotype\u2013Phenotype Correlations"],"prefix":"10.3390","volume":"17","author":[{"given":"Sara Hadj","family":"Sadok","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Hospital Sant Joan de D\u00e9u, 08950 Esplugues de Llobregat, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1427-3707","authenticated-orcid":false,"given":"Alicia Irene","family":"Serra","sequence":"additional","affiliation":[{"name":"Center for Genomic Medicine, Parc Taul\u00ed Hospital Universitari, Institut d\u2019Investigaci\u00f3 i Innovaci\u00f3 Parc Taul\u00ed (I3PT-CERCA), Universitat Aut\u00f2noma de Barcelona, 08193 Sabadell, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1608-841X","authenticated-orcid":false,"given":"Leticia Diana","family":"Pias-Peleteiro","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Hospital Sant Joan de D\u00e9u, 08950 Esplugues de Llobregat, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Diana Salinas","family":"Chaparro","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Hospital Sant Joan de D\u00e9u, 08950 Esplugues de Llobregat, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Clara","family":"Xiol","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Hospital Sant Joan de D\u00e9u, 08950 Esplugues de Llobregat, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0588-9307","authenticated-orcid":false,"given":"Judith","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Hospital Sant Joan de D\u00e9u, 08950 Esplugues de Llobregat, Spain"},{"name":"Institut de Recerca Sant Joan de D\u00e9u, 08950 Esplugues de Llobregat, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras, 28029 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Encarna","family":"Guill\u00e9n-Navarro","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Hospital Sant Joan de D\u00e9u, 08950 Esplugues de Llobregat, Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras, 28029 Madrid, Spain"},{"name":"Departament of Medical Genetics, Hospital Cl\u00ednico Universitario Virgen de la Arrixaca, 30120 El Palmar Murcia, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0960-3153","authenticated-orcid":false,"given":"Antonio F.","family":"Mart\u00ednez-Monseny","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Hospital Sant Joan de D\u00e9u, 08950 Esplugues de Llobregat, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.ajhg.2015.07.004","article-title":"Mutations in DDX3X Are a Common Cause of Unexplained Intellectual Disability with Gender-Specific Effects on Wnt Signaling","volume":"97","author":"Madsen","year":"2015","journal-title":"Am. 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Autism"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/5\/551\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T08:18:50Z","timestamp":1777969130000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/17\/5\/551"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,5]]},"references-count":15,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["genes17050551"],"URL":"https:\/\/doi.org\/10.3390\/genes17050551","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,5]]}}}