Premature Fusion of the Spheno-Occipital Synchondrosis (SOS) and Midface Hypoplasia In Syndromic Craniosynostosis

Background: The spheno-occipital synchondrosis (SOS) is a key player in the proper development of the cranial vault. Its premature fusion has been associated with midface hypoplasia in animal models and been suggested as the etiology of syndromic craniosynostosis. The purpose of this study was to compare CT scans of patients with syndromic bicoronal craniosynostosis and midface hypoplasia, nonsyndromic bicoronal craniosynostosis and healthy controls.

Methods: 69 head CT-scans of syndromic craniosynostosis (47 Apert and 22 Muenke syndrome),12 of non-syndromic, and 76 control patients were assessed.  There were 32 male and 15 female Apert’s patients and 11 male and female Muenke’s patients. The non-syndromic group consisted of 4 males and 11 females.  There were 39 males and 37 female controls. SOS fusion on axial images was graded as open, partially closed, or closed by three blinded reviewers. Groups were further assessed according to gender.  Special attention was focused on ages 2 to 14 years as no control patient fused prior to age 2 or had failed to fuse after age 14. The Fisher exact and ANOVA tests was used to compare groups.

Results: All syndromic patients between ages 7 to 14 had some degree of closure of the SOS, compared to none of the non-syndromic synostosis patients (p=0.05).  Patients demonstrated partial fusion as early as age 2 in Apert’s patients in both males and females (at an average age of 7 in both genders).  Full fusion was observed at an average age of 11 in females and 12 in males.  Male Apert’s patients fused completely significantly earlier compared to males in the non-synostosis group (p=0.008) and the control group (p=0.069) although this was not significant. This phenomenon was not observed in Muenke’s patients.

Conclusions: The SOS closes significantly earlier in patients with syndromic craniosynostosis than non-syndromic synostosis. In male Apert’s patients, complete fusion occurred significantly earlier than in non-synostotic and Muenke’s patients.  These findings are consistent with the typically more severe presentation of midface hypolplasia found in Apert’s compared to Muenke’s patients, suggesting a role of premature closure of the SOS and the degree of midface hypoplasia.  Further work is needed to establish causality between premature fusion of the SOS and growth arrest of the midface in syndromic craniofacial patients.