Prenatal and postmortem characterization of FGFR2-related fetal craniosynostosis: emphasizing rare and atypical anomalies

Abstract

Objective Craniosynostosis (CS) is the second most common craniofacial birth defect after orofacial clefts. Genetic counseling is essential for reproductive planning in affected families.Methods Nine fetal CS cases-six Apert syndrome (AS) and three Pfeiffer syndrome (PS)-with established genetic causes were retrospectively analyzed for clinical, radiological, and molecular features.Results Mean gestational age at first examination was 26.2 weeks. Four AS and two PS cases were diagnosed during the prenatal stage by ultrasonography (USG), whereas two AS and one PS cases were identified during postmortem. Common prenatal findings included polyhydramnios, high flat forehead, and syndactyly. Two of the three cases diagnosed at the postmortem stage had multiple congenital anomalies (MCA), while in the third, CS was suspected due to frontal bossing and proptosis despite the absence of classic signs. All cases carried pathogenic FGFR2 variants.Conclusions Proptosis, frontal bossing, and trigonocephaly are key prenatal indicators of CS, but their absence-especially with systemic anomalies-can challenge diagnosis. In cases with MCA, CS should be suspected even if classic signs are absent, particularly when syndactyly accompanies other complex abnormalities. Postmortem evaluation and molecular genetic testing are essential for definitive diagnosis, especially when clinical features are ambiguous.