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

Abstract

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.

A case report of a patient with Pfeiffer syndrome, an FGRF 2 mutation (Trp290Cys) and unique ocular anterior segment findings

“…1 Mild variants tend to be familial and carry a relatively good prognosis. 6 More severe presentations of Pfeiffer syndrome have subsequently been described which may include severe craniostenosis, extreme proptosis, upper airway obstruction from cartilaginous sleeve anomalies of the trachea or bilateral choanal atresia, and ankylosis of elbows. 2 These severe forms carry a poor prognosis and tend to be sporadic rather than familial.…”

“…2 Less commonly, anterior segment anomalies have been described in patients with Pfeiffer syndrome, including limbal scleralization, corectopia, iris colobomas. [3][4][5][6] Some of these cases have been linked to mutations in the FGFR2 gene. We describe a patient with Pfeiffer syndrome with a unique constellation of ocular anterior segment anomalies which include microcornea, limbal scleralization, corectopia and glaucoma and a mutation in the FGFR2 gene (Trp290Cys).…”

Craniosynostosis in Alagille syndrome

“…The predominant abnormalities are anterior chamber defects (posterior embryotoxon or Axenfeld anomaly) [Puklin et al, 1981]. Ocular anterior chamber abnormalities have been recently described in craniosynostosis syndromes with a mutation in FGFR2 [Okajima et al, 1999]. Vertebral anomalies are also a common finding in AGS, characteristically butterfly vertebrae [Rosenfield et al, 1980].…”

Ser351Cys mutation in the fibroblast growth factor receptor 2 gene results in severe Pfeiffer syndrome

“…The severity of clinical problems is often difficult to predict. The literature contains 12 described cases with Ser351Cys mutations, all of whom have severe craniosynostosis and other medical problems (Pulleyn et al, 1996;Chun et al, 1998;Gripp et al, 1998;Mathijssen et al, 1998;Okajima et al, 1999). With a few exceptions, the prognosis with cloverleaf skull is poor, regardless of the molecular defect.…”