A Rare Craniosynostosis Phenotype Associated With a Homozygous CYP26B1 Pathogenic Variant in the Absence of Extremity...

CYP26B1, a member of the cytochrome P450 enzyme family, is one of the enzymes responsible for the inactivation of retinoic acid. Pathogenic variants in genes involved in endogenous retinoic acid production and control can result in craniofacial disorders and extremity abnormalities. The patient was referred due to craniosynostosis and dysmorphic appearance at the age of 3 years. Clinical exome sequencing showed a likely pathogenic homozygous missense variant, c.1190G>A (p.Arg397Gln), in exon 5 of the CYP26B1 gene. Nine cases with craniosynostosis, various skeletal deformities, arachnodactyly, and encephalocele have been reported in the literature so far, caused by biallelic pathogenic variants in the CYP26B1. All patients had a fusion of various bones in the upper extremity, in addition to premature closure of the skull sutures. Although our patient had craniosynostosis, there was no additional obvious joint synostosis. Herein, we describe a case of an extremely rare skeletal disorder caused by a pathogenic variant in CYP26B1. We broaden the phenotypic spectrum and underscore that extremity joint fusions are not a universal finding of the disease.