Purpose

There are limited population-based analyses of craniofacial anomalies and no prior studies that focus specifically on craniofacial (CF) anomalies of ophthalmic significance. Determining the association between CF anomalies and ophthalmologic diagnoses such as strabismus and keratoconus is important to inform screening practices in this population. This is the first study to report the population-based incidence of CF anomalies with ophthalmic significance and the demographic, clinical, and ophthalmologic characteristics of affected patients.

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Methods

This multi-center, retrospective, population-based cohort study included all patients <5 years of age identified by the Rochester Epidemiology Project who were assigned an included International Classification of Disease (ICD) code (CF diagnoses with ophthalmic significance) while residing in Olmsted County, Minnesota, from January 1, 1986, through December 31, 2023. Medical records were manually reviewed, and cases were excluded if the captured diagnosis code was not relevant following specialty evaluation. Demographic, clinical, and ophthalmologic data were recorded. Incidence rates for each craniofacial anomaly were calculated (per 100,000 person-years) using age- and sex-specific population figures from Olmsted County. Rates were then age- and sex-adjusted to the U.S. annual census population, and 95% confidence intervals were calculated.

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Results

A total of 83 patients were included; 49 (59.0%) were male and 34 (41.0%) were female (p = 0.12). The overall age- and sex-adjusted incidence of craniofacial anomalies was 16.7 per 100,000 person-years (95% CI, 13.1–20.3). When stratified by sex, the incidence was 14.1 per 100,000 person-years (95% CI, 9.3–18.8) in females and 19.2 per 100,000 person-years (95% CI, 13.9–24.6) in males. Among the 83 included patients, the most frequent final clinical diagnoses were trigonocephaly/metopic synostosis (18 cases) and sagittal synostosis (15 cases). These were followed by Pierre Robin sequence (7 cases) and Crouzon syndrome (5 cases). Other relatively common diagnoses included hypertelorism with syndromic features (4 cases), as well as Klippel-Feil syndrome, coronal synostosis, microcephaly, and micrognathia/retrognathia with syndromic features, each accounting for 3 cases. Diagnoses seen in 2 cases each were hemifacial microsomia, Saethre-Chotzen syndrome, and Sotos syndrome. The remaining diagnoses were each represented by a single case, including achondroplasia, Apert syndrome, CBL-related disorder, Cri du chat syndrome, Gabriele-de Vries syndrome, Grieg cephalopolysyndactyly syndrome, MPPH syndrome, Muenke syndrome, oral-facial-digital syndrome, Pfeiffer syndrome, PTEN hamartoma tumor syndrome, Stickler syndrome, Townes-Brocks syndrome, trisomy 13, unspecified congenital craniosynostosis, and velocardiofacial syndrome. Median age at diagnosis was 6 months (IQR 1-17). Relevant clinical history included multiple gestation in 11 patients (13.3%), a family history of craniofacial disorders in 7 (8.4%), and intrauterine growth restriction in 7 (8.4%). Fifty-four of the 83 patients underwent at least one ophthalmologic exam. Among these, 2 (3.7%) were diagnosed with keratoconus and 17 (31.5%) with strabismus. Twelve cases of strabismus (70.6%) were purely horizontal, 1 (5.9%) was vertical, and 4 (23.5%) had combined horizontal/vertical components. Five (29.4%) of these patients eventually underwent strabismus surgery.

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Conclusion

Craniofacial anomalies are rare conditions but can have significant orbital and ophthalmologic implications. The prevalence of ophthalmologic comorbidities, particularly strabismus, supports consideration of routine early ophthalmic screening in these patients. Population-based incidence data from this study can inform clinical care and guide future research efforts.

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Additional Authors

First name	Last name	Base Hospital / Institution
Kerri	McInnis-Smith	Mayo Clinic
Grayson	Ashby	Mayo Clinic
Bhoomi	Dave	Mayo Clinic
Ross	Dierkhising	Mayo Clinic
Waleed	Gibreel	Mayo Clinic

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