Does the Mutation Type Affect the Response to Cranial Vault Expansion in Children With Apert Syndrome?

Abstract

Most cases of Apert syndrome are caused by mutations in the FGFR2 gene, either Ser252Trp or Pro253Arg. In these patients, over the last decades, spring-assisted posterior vault expansion (SA-PVE) has been the technique of choice for cranial vault expansion in the Craniofacial Unit of Great Ormond Street Hospital for Children (GOSH), London. The aim of this study was to investigate if there is a difference in preoperative intracranial volume (ICV) in patients with Apert syndrome with Ser252Trp or Pro253Arg mutation and whether these mutations affect the change in ICV achieved by SA-PVE. The GOSH craniofacial SA-PVE database was used to select patients with complete genetic testing and preoperative and postoperative computed tomography scans. ICV was calculated using FSL (FMRIB Analysis Group, Oxford) and adjusted based on Apert-specific growth curves. Sixteen patients were included with 8 having Ser252Trp mutation and 8 having Pro253Arg mutation. The mean preoperative adjusted computed tomography volume for patients in the Ser252Trp group was 1137.7 cm3 and in the Pro253Arg group was 1115.8 cm3 (P=1.00). There was a significant increase in ICV following SA-PVE in all patients (P<0.001) with no difference in mean change in ICV between the groups (P=0.51). Four (50%) patients with Ser252Trp mutation and 3 (37.5%) with Pro253Arg mutations required a second operation after primary SA-PVE. The results demonstrate that regardless of the mutation present, SA-PVE was successful in increasing ICV in patients with Apert syndrome and that a repeat volume expanding procedure was required by a similar number of patients in the 2 groups. Level of Evidence: III.

Discussion of “Does the Mutation Type Affect the Response to Cranial Vault Expansion in Children With Apert Syndrome?”

“…The article written by Goodarz and collaborators entitled “Does the mutation type affect the response to cranial vault expansion in children with Apert syndrome?” sheds important light on a rarely addressed topic in craniofacial surgery 1. A detailed understanding as to whether and to what degree, if any, genetic mutation affects potential outcomes following posterior cranial vault expansion is fundamental to determining appropriate surgical technique, consolidation periods, and achieving improved outcomes.…”

“…One of the main characteristic of Apert syndrome patients highlighted by the authors1 is the cranial base sutures fusion resulting in markedly turricephaly, which tend to worsen over time, creating a stigmata in a significant number of Apert syndrome patients. Studies have shown reduced turricephaly in Apert patients who undergo prophylactic posterior vault expansion with distraction osteogenesis 5,6.…”

“…It is interesting to read that The Great Ormond Street Hospital for Children craniofacial group advocates deferring posterior vault expansion until the patient presents elevated intracranial pressure (ICP). 1 SOBRAPAR Hospital is the primary Apert syndrome center in Brazil and receives referrals from all over the country, including regions with limited financial resources. It is not feasible to routinely monitor the ICP of all of these syndromic patients.…”

Genetic Subtypes of Apert Syndrome Are Associated With Differences in Airway Morphology and Early Upper Airway Obstruction

“…For example, a recent study described similar intracranial volumes and postoperative response to spring-assisted posterior cranial vault expansion for both Apert genetic subtypes, 7 suggesting they may demonstrate similar cranial morphologies. 7 However, others have described the presence of distinct suture fusion patterns in Apert syndrome which impact cranial growth, suggesting phenotypic variability. 8,9 Case studies have quoted higher rates of upper airway obstruction in patients with Ser252Trp mutations; however, these cases have not been pooled or formally analyzed to date.…”

“…Attempts to associate genotype with craniofacial phenotype have yielded conflicting results. For example, a recent study described similar intracranial volumes and postoperative response to spring-assisted posterior cranial vault expansion for both Apert genetic subtypes, 7 suggesting they may demonstrate similar cranial morphologies 7 . However, others have described the presence of distinct suture fusion patterns in Apert syndrome which impact cranial growth, suggesting phenotypic variability 8,9 .…”