Prenatal ultrasound diagnosis of a case of Pfeiffer syndrome without cloverleaf skull and review of the literature

Pfeiffer syndrome is characterized by bilateral coronal craniosynostosis, midface hypoplasia, beaked nasal tip, broad and medially deviated thumbs and great toes. Originally, it was described in eight persons from three generations in a pedigree consistent with an autosomal dominant transmission. Since then, several reports have documented its high clinical and genetic heterogeneity. The condition is usually detected in the newborn period or later, and very few prenatal ultrasound diagnoses have been reported. We present a case of Pfeiffer syndrome prenatally diagnosed at 20 weeks' gestation, in which the sonographic features of craniosynostosis, hypertelorism associated with an extreme proptosis, and broad thumb led to the diagnosis, confirmed after termination of pregnancy by dysmorphological, pathological and radiological evaluation. DNA analysis of the fibroblast growth factor receptor 2 (FGFR2) showed a missense mutation consisting in a transversion G → C at nucleotide 870. This led to a Trp290Cys amino acidic substitution. We discuss the relevant findings of our and previously published cases. Our report demonstrates that a careful sonographic examination can lead to an early prenatal diagnosis of Pfeiffer syndrome also in cases without cloverleaf skull. Copyright © 2004 John Wiley & Sons, Ltd.