The Clinical and Molecular Spectrum of Turkish Patients with Syndromic Craniosynostosis: A Single Center Study

Syndromic craniosynostosis is caused by pathogenic variants in genes regulating suture development. This study aims to investigate clinical and molecular characteristics in syndromic craniosynostosis.

This retrospective descriptive study included 53 patients from 40 families with syndromic craniosynostosis. Molecular testing was performed in 22 families.

The study included Saethre-Chotzen (n=14), Apert (n=12), Crouzon (n=11), Pfeiffer (n=4), Muenke (n=4), and Carpenter (n=1) syndromes, Crouzon syndrome with acanthosis nigricans (n=2), craniosynostosis with dental anomalies (n=2), craniosynostosis type 4 (n=2), and hypochondroplasia with craniosynostosis (n=1). Genetic etiology was identified in 20 families involving six genes: FGFR1 (Pfeiffer), FGFR2 (Apert, Crouzon, Pfeiffer), FGFR3 (Crouzon with acanthosis nigricans, Muenke), TWIST1 (Saethre-Chotzen), ERF (Craniosynostosis type 4), and IL11RA (Craniosynostosis with dental anomaly). Additionally, a FGFR3 variant causing hypochondroplasia was identified in a patient with multisuture synostosis. Familial inheritance was identified in 25%, but not in Apert syndrome. Brachycephaly (28.3%) was the most common cranial abnormality, followed by plagiocephaly (22.6%). Apert syndrome was characterized by frequent cardiac anomalies, cleft palate, developmental delay, and a higher rate of surgical intervention. In contrast, Crouzon, Pfeiffer, Saethre-Chotzen, and Muenke syndromes showed favorable outcomes, although a fatal course was observed in a patient with Crouzon syndrome with acanthosis nigricans. Rare etiologies included ERF-related craniosynostosis with mild craniofacial findings and IL11RA-related craniosynostosis with intrafamilial phenotypic heterogeneity.

This study describes clinical features of well-defined syndromes such as Apert, Crouzon, and Pfeiffer; reports craniosynostosis in hypochondroplasia; and documents rare ERF- and IL11RA-related forms, highlighting the importance of combining clinical and molecular diagnostics.