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The <jats:italic>SETD2<\/jats:italic> gene encoding a H3K36 trimethyltransferase is implicated in Sotos\u2010like syndrome. This syndrome is characterized by postnatal overgrowth, macrocephaly, obesity, speech delay, and advanced carpal ossification. We report four new patients with constitutional <jats:italic>SETD2<\/jats:italic> mutations and review nine earlier reported patients. Almost all patients presented with macrocephaly associated with advanced stature and obesity in half of the cases. In addition to these principal manifestations, neurodevelopmental disorders are common such as intellectual disability (83%), autism spectrum disorders (89%), and behavioral difficulties (100%) with aggressive outbursts (83%). A variety of features such as joint hypermobility (29%), hirsutism (33%), and naevi (50%) were also reported. Constitutional <jats:italic>SETD2<\/jats:italic> mutations are intragenic loss\u2010of\u2010function variants with truncating (69%) and missense (31%) mutations. Functional studies are necessary to improve understanding of the pathogenicity of some missense <jats:italic>SETD2<\/jats:italic> mutations.<\/jats:p>","DOI":"10.1002\/ajmg.c.31746","type":"journal-article","created":{"date-parts":[[2019,10,23]],"date-time":"2019-10-23T19:28:10Z","timestamp":1571858890000},"page":"509-518","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["<i>SETD2<\/i> related overgrowth syndrome: Presentation of four new patients and review of the literature"],"prefix":"10.1002","volume":"181","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6715-9652","authenticated-orcid":false,"given":"Pauline","family":"Marzin","sequence":"first","affiliation":[{"name":"Department of Medical Genetics INSERM UMR 1163, Paris Descartes\u2010Sorbonne Paris Cit\u00e9 University, IMAGINE Institute, Necker Enfants Malades Hospital  Paris 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