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PURPOSE:The spheno-occipital synchondrosis (SOS) is an important driver of facial and cranial base growth, and its premature fusion is associated with the development of midface hypoplasia in animal models. The current study aims to characterize the fusion of the SOS in patients with Crouzon, Apert and Pfeiffer syndrome and correlate early fusion with the presence of midface hypoplasia.
METHODS:A retrospective case-control study was performed of all patients with Apert, Crouzon, and Pfeiffer syndrome treated at a large craniofacial center between 1984 and 2012. CT scans performed as part of the normal pre-operative evaluation were analyzed for status of SOS patency. Age/gender matched control CT scans were identified from a population of trauma patients and were also assessed of for status of SOS patency. Patients were excluded whose CT scans were of poor quality and prevented adequate SOS assessment. Axial images of all CT scans were categorized as demonstrating either an open, partially fused, or completely fused SOS, and the patient age at each scan was recorded. Midface hypoplasia as determined by SNA measurement at the time of midface surgery was then correlated to SOS status. McNemar’s test for matched pair correlation and linear regression were used to assess significance of findings.
RESULTS:During the study period, a total of 54 patients with 206 CT scans met the inclusion criteria. 206 age/gender matched control scans were also identified. Average age at CT scan was 6.1 years. Table 1 describes the SOS status of cases and controls. The earliest age of partial and complete fusion was 1.1 and 7.0 years, respectively, among cases and 6.2 and 12.7, respectively, among controls. When comparing matched case-control pairs, there were 65 instances of concordant SOS patency and 74 instances of concordant SOS fusion. In 67 case-control pairs, there was discordance between patency and fusion with the odds of CT demonstrated SOS fusion in case CT scans 66.0 (95%CI 9.2-475.5, p<0.000001) times that of controls. 45 patients had adequate radiographic studies for cephalometric analysis with an average SNA angle of 68 (range: 58-80, p<0.0001) degrees. In the 22 cases with multiple CT scans who initially demonstrated open SOS, average age of first evidence of SOS closure was 3.5 (range: 0.5-6.0) years. In this group, average SNA at time of midface surgery was 67.5 (range: 58-76) degrees. Linear regression analysis demonstrated positive correlation with earlier age of first SOS closure and smaller SNA angles (r=0.48, p=0.028).
CONCLUSION:The SOS closes significantly earlier in patients with syndromic craniosynostosis compared with age-matched controls. Moreover, there was a significant positive correlation between earlier evidence of SOS closure and degree of midface hypoplasia, though definitive causality cannot be concluded by this methodology. This is the first study to demonstrate such a correlation in human subjects, and it may provide insight for another therapeutic target to allow for a more normal growth trajectory in the midface of these patients.

SOS Status by Diagnosis

	No of Patients	Open SOS	Partially Fused SOS	Completely Fused SOS	Total No of CTs
Apert	15	0	19 (50%)	19 (50%)	38
Crouzon	24	38 (34%)	43 (38%)	31 (28%)	112
Pfeiffer	15	27 (48%)	23 (41%)	6 (11%)	56
Total	54	65 (32%)	85 (41%)	56 (27%)	206
Controls	206	132 (64%)	42 (20%)	32 (16%)	206