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An initial report of four individuals described a syndrome of fetal and infantile lethality with craniosynostosis and skeletal anomalies caused by homozygous pathogenic missense variants in <jats:italic>CYP26B1<\/jats:italic>. In contrast, a 22\u2010year\u2010old female was reported with a homozygous missense pathogenic variant in <jats:italic>CYP26B1<\/jats:italic> with complex multisuture craniosynostosis and intellectual disability, suggesting that in some cases, biallelic pathogenic variants of <jats:italic>CYP26B1<\/jats:italic> may be compatible with life. Here we describe four additional living individuals from two families with compound heterozygous pathogenic missense variants in <jats:italic>CYP26B1<\/jats:italic>. Structural assessment of these additional missense variants places them further from the catalytic site and supports a model consistent with milder nonlethal disease. In addition to previously reported findings of multisuture craniosynostosis, conductive hearing loss, joint contractures, long slender fingers, camptodactly, broad fingertips, and developmental delay\/intellectual disability, skeletal imaging in our cases also revealed gracile long bones, gracile ribs, radioulnar synostosis, and carpal and\/or tarsal fusions. These individuals broaden the phenotypic range of biallelic pathogenic variants in <jats:italic>CYPB26B1<\/jats:italic> and most significantly clarify that mortality can range from perinatal lethality to survival into adulthood.<\/jats:p>","DOI":"10.1002\/ajmg.a.62387","type":"journal-article","created":{"date-parts":[[2021,6,23]],"date-time":"2021-06-23T07:37:22Z","timestamp":1624433842000},"page":"2766-2775","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Nonlethal presentations of <scp>CYP26B1<\/scp>\u2010related skeletal anomalies and multiple synostoses syndrome"],"prefix":"10.1002","volume":"185","author":[{"given":"Katheryn","family":"Grand","sequence":"first","affiliation":[{"name":"Division of Medical Genetics Cedars Sinai Medical Center  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5030-4692","authenticated-orcid":false,"given":"Cara M.","family":"Skraban","sequence":"additional","affiliation":[{"name":"Division of Human Genetics Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"},{"name":"Department of Pediatrics University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jennifer L.","family":"Cohen","sequence":"additional","affiliation":[{"name":"Division of Medical Genetics, Department of Pediatrics Duke University School of Medicine  Durham North Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leah","family":"Dowsett","sequence":"additional","affiliation":[{"name":"Kapi'olani Medical Center  Honolulu Hawai'i USA"},{"name":"Department of Pediatrics University of Hawai'i John A. 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