Prenatal exclusion of Crouzon syndrome by mutation analysis of FGFR2

Crouzon Syndrome is an autosomal dominant syndromic craniosynostosis characterized by premature closure of cranial sutures, exophthalmos, and midface hypoplasia. It is caused by multiple mutations in the fibroblast growth factor receptor 2 (FGFR2). We describe prenatal genetic testing of FGFR2 in a fetus of a mother whose previous child had Crouzon Syndrome due to an apparently de novo mutation, S351C. Sequence electropherograms of the exon 10 of FGFR2 encompassing the codon 351 revealed only the normal sequence, thus predicting a very high likelihood of an unaffected fetus. The study was confirmed by the birth of a normal neonate. We report the use of molecular genetic testing to exclude Crouzon Syndrome due to FGFR2 mutation prenatally. Prenatal diagnostic testing for a known mutation is a reasonable option for couples at risk for having a child with Crouzon Syndrome due to germline mosaicism. Molecular testing is more accurate and reliable than ultrasonography and provides families with reassurance.