Ocular anterior chamber dysgenesis in craniosynostosis syndromes with a fibroblast growth factor receptor 2 mutation.

Fibroblast growth factor receptor (FGFR) mutations have been found in craniosynostosis syndromes with and without limb and/or dermatologic anomalies. Ocular manifestations of FGFR2 syndromes are reported to include shallow orbits, proptosis, strabismus, and hypertelorism, but no ocular anterior chamber, structural abnormalities have been reported until now. We evaluated three unrelated patients with severe Crouzon or Pfeiffer syndrome. Two of them had ocular findings consistent with Peters anomaly, and the third patient had opaque corneae, thickened irides and ciliary bodies, and shallow anterior chambers with occluded angles. Craniosynostosis with and without cloverleaf skull deformity, large anterior fontanelle, hydrocephalus, proptosis, depressed nasal bridge, choanal stenosis/atresia, midface hypoplasia, and elbow contractures were also present. These patients had airway compromise, seizures, and two died by age 15 months. All three cases were found to have the same FGFR2 Ser351Cys (1231C to G) mutation predicted to form an aberrant disulfide bond(s) and affect ligand binding. Seven patients with isolated Peters anomaly, two patients with Peters plus syndrome, and three cases with typical Antley-Bixler syndrome were screened for this mutation, but none was found. These phenotype/genotype data demonstrate that FGFR2 is involved in the development of the anterior chamber of the eye and that the Ser351Cys mutation is associated with a severe phenotype and clinical course. Am. J. Med. Genet. 85:160–170, 1999. © 1999 Wiley-Liss, Inc.