The Spheno-Occipital Synchondrosis Fuses Prematurely in Patients With Crouzon Syndrome and Midface Hypoplasia Compared With Age- and Gender-Matched Controls

Abstract

Premature closure of the spheno-occipital synchondrosis (SOS) has been associated with midface hypoplasia in animal models and patients with specific forms of syndromic craniosynostosis. The present study aimed to characterize SOS fusion in patients with Crouzon syndrome. A case-control study was performed in patients with Crouzon syndrome treated at the Children's Hospital of Philadelphia from 1984 to 2012. The cases included patients with Crouzon syndrome and at least 1 high-quality computed tomography (CT) scan in which SOS patency could be assessed. Age- and gender-matched control CT scans were identified for comparison. The patient age at the CT scan was evaluated as the predictor, with SOS patency identified as the outcome variable. Three independent reviewers with high inter-rater reliability graded the SOS patency as open, partially fused, or completely fused. The Wilcoxon rank sum test was used to compare the Crouzon group and the controls. During the study period, 30 patients were identified with Crouzon syndrome. A total of 24 patients, all with midface hypoplasia and with 112 cranial CT scans, met the inclusion criteria. Accordingly, 112 age- and gender-matched control CT scans were assessed. No patient in the control group had midface hypoplasia. Within the Crouzon group, the average age at complete closure (14.0 ± 3.4 years) evident on the CT scan was significantly younger than that in the control group (16.6 ± 2.2 years; P = .0152). The average age when the scans showed complete patency of the SOS in the Crouzon group (1.3 ± 1.1 years) was significantly younger than that in the control group (3.2 ± 2.3 years; P = .0001). The SOS closes significantly earlier in patients with Crouzon syndrome compared with age- and gender-matched controls. The strong statistical correlation supports premature closure of the SOS as a possible mechanistic contributor to midface hypoplasia.