Genetic Heterogeneity, Craniofacial Surgical Burden, and Surgical Techniques in Patients With Saethre-Chotzen Syndrome

Abstract

Objective: While genotype correlates with phenotype in patients with many forms of syndromic craniosynostosis, the relationship between molecular diagnosis and craniofacial surgical history in patients with Saethre-Chotzen syndrome (SCS) is more variable. This manuscript characterizes that relationship and evaluates operative trends in these patients over the past 3 decades. Methods: Demographic information, molecular diagnosis, and craniofacial surgical history in patients born with SCS between 1989 and 2023 were compared with appropriate statistics, including t tests and analysis of variance. Results: Thirty-five patients with SCS were included, and there was no difference in total craniofacial procedures among those with TWIST1 substitutions (2.1 ± 1.6), duplications (3.0 ± 4.2), insertions (3.5 ± 0.7), or deletions (2.4 ± 1.9; P = 0.97). Cranial expansion rates were also similar across all genetic diagnoses (P>0.05), and surgical incidence was similar across patients with unicoronal, bicoronal, and multisuture involvement (P > 0.05). Those with an initial fronto-orbital advancement had a lower incidence of secondary cranial vault procedures compared with those with an initial posterior vault distraction osteogenesis (29% versus 71%, P < 0.05), though this did not control for phenotypic severity. On average, total cranial vault surgical burden (1.35 ± 0.67 versus 1.75 ± 0.46) and cranial expansion surgical burden (1.40 ± 0.68 versus 1.88 ± 0.64) between the fronto-orbital advancement–first and posterior vault distraction osteogenesis–first cohorts were similar (P = 0.11, P = 0.17, respectively). Conclusion: While SCS is molecularly and phenotypically heterogeneous, genetic diagnosis does not appear associated with rates of craniofacial surgery. Additional prospective study of correlations between genotype, severity of craniofacial manifestations, and treatment algorithms is warranted; but, in the end, it may be that this highly variable form of syndromic craniosynostosis warrants tailored, expectant management.