Here, we describe two unrelated families with distinct phenotypes due to novel pathogenic variants in CYP26B1. Compound heterozygous CYP26B1 variants (p.[(Pro118Leu)];[(Arg234Gln)]) in family 1 result in a mild phenotype including a Marfanoid habitus, bony synostosis, learning disability, and abnormal cranial shape without craniosynostosis. This evidence concerns the gene CYP26B1 and craniosynostosis.