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Through description of a large cohort, which doubles the number of reported patients, we further delineate the spectrum of YWHAG<\/jats:italic>\u2010related epilepsy.<\/jats:p><\/jats:sec>Methods<\/jats:title>We included in this study 24 patients, 21 new and three previously described, with pathogenic\/likely pathogenic variants in YWHAG<\/jats:italic>. We extended the analysis of clinical, electroencephalographic, brain magnetic resonance imaging, and molecular genetic information to 24 previously published patients.<\/jats:p><\/jats:sec>Results<\/jats:title>The phenotypic spectrum of YWHAG<\/jats:italic>\u2010related disorders ranges from mild developmental delay to developmental and epileptic encephalopathy (DEE). Epilepsy onset is in the first 2\u2009years of life. Seizure freedom can be achieved in half of the patients (13\/24, 54%). Intellectual disability (23\/24, 96%), behavioral disorders (18\/24, 75%), neurological signs (13\/24,\u200954%), and dysmorphisms (6\/24,\u200925%) are common. A genotype\u2013phenotype correlation emerged, as DEE is more represented in patients with missense variants located in the ligand\u2010binding domain than in those with truncating or missense variants in other domains (90% vs. 19%, p<\/jats:italic>\u2009<\u2009.001).<\/jats:p><\/jats:sec>Significance<\/jats:title>This study suggests that pathogenic YWHAG<\/jats:italic> variants cause a wide range of clinical presentations with variable severity, ranging from mild developmental delay to DEE. In this allelic series, a genotype\u2013phenotype correlation begins to emerge, potentially providing prognostic information for clinical management and genetic counseling.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.17939","type":"journal-article","created":{"date-parts":[[2024,3,16]],"date-time":"2024-03-16T14:29:56Z","timestamp":1710599396000},"page":"1439-1450","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Clinical and molecular characterization of patients with YWHAG<\/i><\/scp>\u2010related epilepsy"],"prefix":"10.1111","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8549-4158","authenticated-orcid":false,"given":"Valentina","family":"Cetica","sequence":"first","affiliation":[{"name":"Neuroscience Department Meyer Children\u2019s Hospital IRCCS Florence 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