Visual Outcomes in Children with Craniosynostosis: Experience from a National Tertiary Referral Center

Abstract

INTRODUCTION: Craniosynostosis is a rare craniofacial disorder frequently associated with ophthalmologic morbidity. The impact of cranial surgery timing on visual outcomes remains controversial. This study evaluated ophthalmologic outcomes in children with craniosynostosis treated at a national tertiary referral center in Portugal, focusing on the influence of surgical timing and syndromic status on visual function.

METHODS: A retrospective study included all children with genetically or clinically confirmed craniosynostosis assessed by ophthalmology and neurosurgery departments between January 2014 and August 2025. Demographic, genetic, surgical and ophthalmic data were collected. Patients were categorized by surgical timing: early (≤ 6 months) or late surgery (>6 months). Logistic regression models assessed associations between surgical timing, syndromic status and visual outcomes.

RESULTS: Thirty-seven patients were included (76% syndromic). Multiple-suture involvement occurred in 21 (57%), with the coronal suture most frequently affected (41%). Median age at the first neurosurgery was 7.0 months (IQR 4.0-16.5). Genetically confirmed syndromic craniosynostosis was present in 27 patients (73%), most commonly Crouzon (n=9), Muenke (n=5), Apert (n=4) and Pfeiffer (n=3). Nineteen distinct pathogenic variants were identified, predominantly in the FGFR2 gene (n=7) and FGFR3 (n=5), with novel variants in GLI3 and EFNB1.

Late surgery was associated with higher odds of amblyopia (OR=2.75; 95% CI:0.50-14.99; p=0.243). Syndromic craniosynostosis independently conferred a ten-fold increased risk of strabismus (OR=10.23; 95% CI: 1.61-64.8; p=0.014) and a greater risk of amblyopia (OR=3.46; 95% CI: 0.35-34.42; p=0.289). Multiple-suture involvement displayed a trend toward optic atrophy (OR=3.57; p=0.23). At baseline, 38.5% had amblyopia, 66.7% strabismus and 81.1% papilledema. At final follow-up (mean 6.5 years), amblyopia persisted in 28.6%, strabismus in 78.4%, and optic atrophy developed in 21.6%; papilledema resolved in all.

CONCLUSION: This first Portuguese cohort integrating clinical, surgical and genetic data underscores the significant visual morbidity of craniosynostosis. Syndromic status emerged as the main determinant of adverse ophthalmologic outcomes, while earlier cranial surgery showed a potentially protective effect on visual development. The identification of novel pathogenic variants expands the molecular spectrum of craniosynostosis. Early referral, comprehensive genetic evaluation and long-term ophthalmologic surveillance remain crucial to preserve vision in this vulnerable population.