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Exome sequencing of both the children and their mother revealed two novel <jats:italic>PIK3C2A<\/jats:italic> variants in the siblings, c.4381delC (p.Arg1461Glufs*31) and c.1555C\u2009&gt;\u2009T (p.Arg519Ter). PIK3C2A belongs to the Class IIa family of Phosphatidylinositol\u20103\u2010kinases, which create second messenger lipids that regulate a wide range of downstream signaling pathways involved in cell growth, survival and migration. Tiosano et al. (2019) identified the first monogenic disorder associated with biallelic <jats:italic>PIK3C2A<\/jats:italic> loss\u2010of\u2010function variants (oculoskeletodental syndrome). The novel syndrome was characterized by short stature, coarse facial features, ocular and skeletal abnormalities. This report describes two additional siblings affected by the <jats:italic>PIK3C2A<\/jats:italic>\u2010related syndrome, confirms core clinical features, establishes intrafamilial variability and expands the phenotype to include proteinuria.<\/jats:p>","DOI":"10.1002\/ajmg.a.62881","type":"journal-article","created":{"date-parts":[[2022,6,30]],"date-time":"2022-06-30T06:58:38Z","timestamp":1656572318000},"page":"2724-2731","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Expanding the phenotype of <scp><i>PIK3C2A<\/i><\/scp> related syndrome: Report of two siblings with novel features and genotype"],"prefix":"10.1002","volume":"188","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9702-6108","authenticated-orcid":false,"given":"Carolina I.","family":"Galarreta","sequence":"first","affiliation":[{"name":"Medical Genetics and Metabolism Department Valley Children's Hospital  Madera California 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