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From DNA to Diagnosis: Mapping the Landscape of Craniosynostosis Genetics
Viraj Govani, BA*
Mary Wilding, BS*
Janina Kueper, MD
Luis Espinoza, BA
Tobi Somorin, BS
Ashley Rogers, MD
Jesse Goldstein, MD
University of Pittsburgh School of Medicine
2025-01-09
Presenter: Viraj Govani
Affidavit:
This project is representative of original work from the entire team
Director Name: Jesse Goldstein
Author Category: Medical Student
Presentation Category: Clinical
Abstract Category: Craniomaxillofacial
Introduction:
Craniosynostosis, a congenital condition involving premature cranial suture fusion, causes skull deformities and developmental challenges. This study highlights our institution's experience and the role of genetic evaluation in understanding its etiology and how it affects patient trajectories.
Methods:
We retrospectively reviewed our cohort of patients with craniosynostosis (2003–2023), analyzing demographics, clinical data, genetics, surgeries, and outcomes using descriptive statistics, chi-square, and t-tests (p<0.05).
Results:
Among 719 patients with craniosynostosis, 64.3% were male and 83.0% were Caucasian. Genetic testing was performed on 288 patients, most frequently utilizing microarray (n=153), karyotype (n=63), Fragile X testing (n=46), and FGFR testing (n=22). Likely pathogenic variants were identified computationally in 93 patients, with FGFR2 (n=11), FGFR3 (n=7), GALT (n=4), BRAF (n=4), and TCF12 (n=4) being the most common.
Patients with pathogenic FGFR2 variants were morphologically distinct, significantly more likely to have sagittal (p=0.028) and squamosal (p=0.038) craniosynostosis than those without. Furthermore, patients with pathogenic FGFR3 variants were significantly more likely to require posterior vault expansion (p=0.001) than patients without a pathogenic variant. Compared to patients without significant genetic findings, patients with likely pathogenic FGFR2 and FGFR3 variants had a significantly increased risk of requiring follow-up surgery (p=0.011 and p=0.005 respectively).
Conclusion:
While genetic testing is not always conclusive or immediately clinically actionable, our findings suggest testing can confirm syndromic diagnoses with clinically salient consequences. Future research should further explore specific impacts of the identified genetic variants on patient presentations and surgical outcomes.
