Ocular Phenotype Correlations in Patients with TWIST versus FGFR3 Genetic Mutations

Abstract

Introduction: Despite the similar clinical phenotype shared by patients with Saethre–Chotzen and Muenke craniosynostoses, these two syndromes are now genotypically distinct. Patients with Saethre–Chotzen and Muenke craniosynostoses carry mutations in the TWIST and FGFR3 genes, respectively. The purpose of this study was to assess possible ocular phenotypic differences between these two patient groups. Methods: A retrospective chart review was performed for 21 children with known mutations of the TWIST or the FGFR3 genes. Data gathered included patient gender, age, family craniofacial history, craniofacial and ophthalmic surgeries, presence and type of strabismus, ptosis, cycloplegic refraction, visual acuity, presence of amblyopia, nasolacrimal duct obstruction (NLDO), nystagmus, hypertelorism, epicanthal fold anomalies, and any ocular structural abnormalities. Results: Among the 10 patients in the TWIST group, horizontal strabismus was present in 70%, vertical strabismus in 60%, NLDO in 60%, ptosis in 90%, myopia in 30%, hyperopia in 40%, astigmatism in 50%, anisometropia in 30%, nystagmus in 30%, inferior oblique overaction (IOOA) in 40%, and amblyopia in 70%. Among the 11 patients in the FGFR3 group, horizontal strabismus was present in 55%, vertical strabismus in 36%, NLDO in 0%, ptosis in 36%, myopia in 18%, hyperopia in 27%, astigmatism in 9%, anisometropia in 18%, nystagmus in 18%, IOOA in 45%, and amblyopia in 18%. Discussion: Patients with the TWIST gene mutation may have more ophthalmic abnormalities, including more severe strabismus, ptosis, NLDO, astigmatism, double elevator palsy, and amblyopia, compared to patients with the FGFR3 gene mutation. Conclusions: Molecular diagnosis will enable ophthalmologists to better anticipate their patients’ ophthalmic complications, improving both patient counseling and management.