Mutation c.943G>T (p.Ala315Ser) in FGFR2 Causing a Mild Phenotype of Crouzon Craniofacial Dysostosis in a Three-Generation Family.

Crouzon syndrome craniofacial dysostosis type I [OMIM 123500] is caused by mutations in the gene encoding fibroblast growth factor receptor-2 (FGFR2). An overlapping phenotype with Muenke and Crouzon syndrome with acanthosis nigricans (FGFR3 mutations) is known. The clinical diagnosis can be corroborated by molecular studies in about 80-90% of the cases. No clear genotype/phenotype correlation has been identified yet. Here, we describe a second family with a mild phenotype in which the FGFR2 mutation c.943G>T leading to the amino acid substitution p.Ala315Ser was detected. Five affected family members showed craniofacial dysostosis without overt craniosynostosis. They all had midface hypoplasia. Crouzonoid appearance with mild protrusion of bulbi was only apparent in our index patient as well as obstructive sleep apnea episodes leading to reduced oxygen saturation; therefore, surgical intervention was suggested. One other affected family member additionally had iris coloboma.