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

A number of craniosynostotic disorders have recently been ascribed to mutations in genes coding for the fibroblast growth factor receptors(FGFRs). The common feature of these FGFR-associated conditions is the unilateral or bilateral premature ossification of the coronal suture. One distinct craniosynostotic condition is trigonocephaly, which results from the premature fusion 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 progressive involvement of other cranial sutures with age is observed. The possible involvement of mutated FGFRs in trigonocephaly was investigated in nine newborns affected by isolated premature synostosis of the metopic suture. All except one of these cases carried no mutations in the FGFR1-3 domains indicated as hot spots for craniosynostosis-associated mutations. A T(978)C transition in the FGFR2 exon IIIa was found in a patient who had a phenotype that apparently fitted the trigonocephalic condition at birth, but showed additional facial anomalies, which worsened progressively with age towards a Crouzon-like profile. The present finding points out the importance, from both diagnostic and prognostic points of view, of early FGFR mutational screening in craniosynostotic conditions, even in forms that apparently do not involve closure of the coronal suture at birth.

Methimazole embryopathy: delineation of the phenotype.

We report on a further case of congenital anomalies in a child exposed to methimazole during the first trimester of pregnancy (from first to seventh gestational week), and define a specific malformation pattern related to prenatal methimazole exposure and consisting of choanal and esophageal atresia, scalp defects, minor facial anomalies and psychomotor delay.