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Until now, six patients with this condition have been reported in the literature. In addition to skeletal overgrowth, these patients exhibit hyperelastic, translucent, and fragile skin, scoliosis, progressive loss of subcutaneous adipose tissue, skull deformity, infantile myofibromas, neuropsychiatric symptoms, and arachnoid cysts in the posterior fossa and periventricular white matter signal abnormalities on neuroimaging. This constellation of phenotypes clearly distinguishes KOGS from other <jats:italic>PDGFRB<\/jats:italic>\u2010related disorders, including idiopathic basal ganglia calcification, infantile myofibroma, and Penttinen\u2010type premature aging syndrome. From a molecular standpoint, PDGFRB is a dimeric receptor tyrosine kinase that plays critical roles in cell growth and tumorigenesis. The two known types of pathogenic variants (p.(Pro584Arg) and p.(Trp566Arg)) of the <jats:italic>PDGFRB<\/jats:italic> that cause KOGS are exclusively located in the juxtaglomerular domain that regulates autoactivation\/inhibition of PDGFRB. In\u2010vitro evidence suggests that p.(Pro584Arg) represents a gain\u2010of\u2010function pathogenic variant. Inhibition of PDGFRB activity using multi\u2010kinase inhibitors appears to be a potentially promising therapeutic approach. Investigation of the molecular mechanisms underlying the pathogenesis of this disease using induced pluripotent stem cells is under way. Presence of skeletal overgrowth, distinctive facial features, characteristic hyperelastic and fragile skin, and cerebral white matter lesions with neuropsychiatric symptoms should prompt genetic analysis of the <jats:italic>PDGFRB<\/jats:italic>.<\/jats:p>","DOI":"10.1002\/ajmg.c.31755","type":"journal-article","created":{"date-parts":[[2019,11,11]],"date-time":"2019-11-11T18:08:21Z","timestamp":1573495701000},"page":"650-657","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Kosaki overgrowth syndrome: A newly identified entity caused by pathogenic variants in platelet\u2010derived growth factor receptor\u2010beta"],"prefix":"10.1002","volume":"181","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7311-4135","authenticated-orcid":false,"given":"Toshiki","family":"Takenouchi","sequence":"first","affiliation":[{"name":"Department of Pediatrics Keio University School of Medicine  Tokyo 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