FIRST-TRIMESTER PRENATAL-DIAGNOSIS OF CROUZON SYNDROME

Crouzon syndrome, one of the best known of many craniofacial syndromes , is an autosomal dominant disorder characterized by craniosynostosis, prominent eyes, and midfacial hypoplasia due to abnormal development and premature fusion of the skull. Recently mutations in the fibroblas t growth factor receptor 2 gene (FGFR2) were found to cause Crouzon. W e have identified the recurrent mutation C342Y in two unrelated patien ts with Crouzon syndrome. One patient (A) belongs to a family in which Crouzon could be followed in three generations, while the other patie nt (B) represents a sporadic case. The identification of the disease-c ausing mutation allowed first-trimester prenatal diagnosis as requeste d by both patients in their subsequent pregnancies. A chorionic villus biopsy was performed in the 11th gestational week of patient A's preg nancy. DNA isolated from the biopsy revealed a fetus heterozygous for the C342Y mutation, i.e., having Crouzon syndrome. The pregnancy was t erminated and the molecular diagnosis was confirmed later by analysis of fetal and placental tissue. Patient B had a missed abortion before the scheduled chorionic villus biopsy was performed. Mutation analysis of the aborted fetal tissue did not show the C342Y mutation.