Fibroblast growth factor receptor mutational screening in newborns affected by metopic synostosis

A number of craniosynostotic disorders have recently been ascribed to mutat ions in genes coding for the fibroblast growth factor receptors(FGFRs). The common feature of these FGFR-associated conditions is the unilateral or bi lateral premature ossification of the coronal suture. One distinct craniosy nostotic condition is trigonocephaly, which results from the premature fusi on of the metopic suture. Trigonocephaly mostly occurs as isolated cranial defect; however, the premature closure of the metopic suture may represent a feature of more complex craniosynostotic conditions in which a progressiv e involvement of other cranial sutures with age is observed. The possible i nvolvement of mutated FGFRs in trigonocephaly was investigated in nine newb orns affected by isolated premature synostosis of the metopic suture. All e xcept one of these cases carried no mutations in the FGFR1-3 domains indica ted as hot spots for craniosynostosis-associated mutations. A T(978)C trans ition in the FGFR2 exon IIIa was found in a patient who had a phenotype tha t apparently fitted the trigonocephalic condition at birth, but showed addi tional facial anomalies, which worsened progressively with age towards a Cr ouzon-like profile. The present finding points out the importance, from bot h diagnostic and prognostic points of view, of early FGFR mutational screen ing in craniosynostotic conditions, even in forms that apparently do not in volve closure of the coronal suture at birth.