Novel mutation in the FGFR2 gene at the same codon as the Crouzon syndrome mutations in a severe Pfeiffer syndrome type 2 case

We have studied an infant with cloverleaf skull, proptosis, radioulnar synostosis and broad thumbs and great toes diagnosed as Pfeiffer syndrome type 2. However, there were many overlapping findings with Antley-Bixler syndrome. The patient was found to have a G to T mutation in codon 290 exon 7 of the FGFR2 gene leading to a substitution of a cys for the normal trp at this locus. This is the third mutation characterized at this codon; therefore, this locus appears to be a mutational hotspot in the gene. However, the other known mutations lead to a milder, Crouzon-like phenotype. The introduction of an additional cys into a region characterized by immunoglobulin-type loops maintained by cys S-S crosslinking may provide an explanation for the severity of the clinical findings of this child.