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

LEVEL OF EVIDENCE: III.

Results Following Adoption of a Modified Melbourne Technique of Total Scaphocephaly Correction.

The Melbourne technique was described in 2008 as a novel method for complete correction of scaphocephaly. Since 2015, it has become our operation of choice for children with sagittal synostosis who are too old at presentation for minimally invasive techniques. Our modifications were 2-position (initially supine then prone) technique and undertaking a formal fronto-orbital remodeling to correct forehead contour. Retrospective chart review was used to record demographics, blood transfusion frequency and volumes, operating time, length of stay, clinical outcome, and complications. Eleven underwent modified Melbourne procedure between July 2015 and March 2017; 9 of 11 were male. All had a diagnosis of nonsyndromic sagittal synostosis. Mean age at surgery was 29 months. Mean surgical time was 6 hours. All patients required blood transfusion with a mean volume transfused of 29 mL/kg (range 13-83 mL/kg). For those 5 patients where preoperative and postoperative measurements were available, there was an increase in mean cephalic index (CI) from 0.64 to 0.75. All postoperative patients had a CI of over 0.70. Three-dimensional shape analysis indicated head shape change addressing all phenotypic aspects of scaphocephaly. In the 5 patients in which analysis could be undertaken, the mean intracranial volume increased from 1481 cm preoperatively to 1671 cm postoperatively, a mean increase in intracranial volume of 14%. The postoperative intracranial volume was higher than preoperative in all 5 patients. There were 4 minor and no major complications. Modified Melbourne procedure is safe and effective for the treatment of severe scaphocephaly in sagittal synostosis.

Mutations in TCF12, encoding a basic helix-loop-helix partner of TWIST1, are a frequent cause of coronal craniosynostosis.

Craniosynostosis, the premature fusion of the cranial sutures, is a heterogeneous disorder with a prevalence of ∼1 in 2,200 (refs. 1,2). A specific genetic etiology can be identified in ∼21% of cases, including mutations of TWIST1, which encodes a class II basic helix-loop-helix (bHLH) transcription factor, and causes Saethre-Chotzen syndrome, typically associated with coronal synostosis. Using exome sequencing, we identified 38 heterozygous TCF12 mutations in 347 samples from unrelated individuals with craniosynostosis. The mutations predominantly occurred in individuals with coronal synostosis and accounted for 32% and 10% of subjects with bilateral and unilateral pathology, respectively. TCF12 encodes one of three class I E proteins that heterodimerize with class II bHLH proteins such as TWIST1. We show that TCF12 and TWIST1 act synergistically in a transactivation assay and that mice doubly heterozygous for loss-of-function mutations in Tcf12 and Twist1 have severe coronal synostosis. Hence, the dosage of TCF12-TWIST1 heterodimers is critical for normal coronal suture development.

Ocular advancement in monobloc distraction.

BACKGROUND: Monobloc distraction has been demonstrated to be an efficacious, safe, and stable method of providing functional and aesthetic improvement in children with syndromic craniosynostosis. Although the movement of bony structures following monobloc distraction has been quantitatively assessed before, objective analysis of the movement of soft tissues, such as the globe, has not been published previously. The authors present a method that assesses globe movement following monobloc distraction, using computed tomographic scan data. METHODS: The preoperative and postoperative computed tomographic scans of 10 patients with Pfeiffer's and Crouzon's syndromes, undergoing monobloc distraction, were assessed. Scan data were loaded into voxel image-rendering software that produced a three-dimensional reconstruction. Direct measurements between preoperative and postoperative images were taken. RESULTS: An average upper face osseous distraction distance of 12.94 mm, with an average lower face distraction of 14.19 mm, was achieved in all 10 children. The authors measured average globe movements on three planes and calculated an average left eye forward movement of 5.28 mm and average right eye forward movement of 6.33 mm. In all, globe advancement was approximately two fifths of the distance advanced by the surrounding bone. CONCLUSIONS: Forward movement of the globe following monobloc distraction has not previously been described. Although there is no current evidence for optic nerve stretch and compromise in monobloc surgery, the functional implications of these findings should be formally assessed.