New insights into the relationship between suture closure and craniofacial dysmorphology in sagittal nonsyndromic craniosynostosis

Abstract

Premature closure of the sagittal suture occurs as an isolated (nonsyndromic) birth defect or as a syndromic anomaly in combination with other congenital dysmorphologies. The genetic causes of sagittal nonsyndromic craniosynostosis (NSC) remain unknown. Although variation of the dysmorphic (scaphocephaly) skull shape of sagittal NSC cases has been acknowledged, this variation has not been quantitatively studied three-dimensionally (3D). We have analyzed the computed tomography skull images of 43 infants (aged 0.9-9 months) with sagittal NSC using anatomical landmarks and semilandmarks to quantify and characterize the within-sample phenotypic variation. Suture closure patterns were defined by dividing the sagittal suture into three sections (anterior, central, posterior) and coding each section as 'closed' or 'fused'. Principal components analysis of the Procrustes shape coordinates representing the skull shape of 43 cases of NSC did not separate individuals by sex, chronological age, or dental stages of the deciduous maxillary first molar. However, analysis of suture closure pattern allowed separation of these data. The central section of the sagittal suture appears to be the first to fuse. Then, at least two different developmental paths towards complete fusion of the sagittal suture exist; either the anterior section or the posterior section is the second to fuse. Results indicate that according to the sequence of sagittal suture closure patterns, different craniofacial complex shapes are observed. The relationship between craniofacial shape and suture closure indicates not only which suture fused prematurely (in our case the sagittal suture), but also the pattern of the suture closure. Whether these patterns indicate differences in etiology cannot be determined with our data and requires analysis of longitudinal data, most appropriately of animal models where prenatal conditions can be monitored.

Figures

Fig. 1

Superior view of a sagittal suture (anterior fontanelle at top) illustrating sagittal suture closure pattern. Anterior section of sagittal suture ‘closed’ (C), central and posterior section ‘fused’ (F). Consequently, the closure pattern of the sagittal suture is CFF. The black arrow indicates appearance of suture sections we coded as ‘closed’.

Fig. 2

Radiograph and 3D CT surface reconstruction of crown stages showing deciduous first molar. Stage A: beginning of mineralization at cusp tips. Stage B: coalescence of cusp tips to form a regularly outlined occlusal surface. Stage C: occlusal surface is complete. Approximal edges of forming crown has reached future contact areas. Stage D: crown (enamel) is complete with full-thickness occlusal dentin present, and roof of the pulp chamber is mature. Beginning of root formation is seen (modified after Liversidge & Molleson, 2004).

Fig. 3

Illustration of the 222 points measured on 3D reconstruction of computed tomography scans of each individual in our sample. Anatomical landmarks (Table 2) are shown in blue, curve semilandmarks are shown in red, and surface semilandmarks are shown in green. Top left: endocranial surface of the cranial base, top right: anterior view, bottom left: lateral view, bottom right: inferior view.

Fig. 4

Placement of the individuals on PC1 and PC2 in the shape space (principal components analysis of the Procrustes shape coordinates using all landmarks and semilandmarks of the 43 infants with sagittal NSC). Male infants are denoted by triangles while circles denote female infants. Ages of individuals are indicated by colour: white = 0–3 months, gray = 3–6 months, black = 6–9 months.

Fig. 5

Mean and 0.95 confidence interval plot of centroid size (CS) grouped by sagittal suture closure pattern (C: closed, F: fused).

Fig. 6

Placement of the individuals on PC1 and PC2 in the shape space defined by the principal components analysis of the Procrustes shape coordinates using all landmarks and semilandmarks of the 43 infants with sagittal NSC. Individuals are coded for suture closure pattern (closed: C, fused: F). Convex hulls (transparent) are drawn for the CFC, CFF, and FFC groups.

Fig. 7

Superimposed warped skulls according to PC1 (left) and PC2 (right). Lateral views of endocranial surface viewed through a mid-sagittal section (top) and superior view of endocranial surface of axial sections (bottom). The blue warped skull corresponds to −0.05PC1 and the red warped skull corresponds to +0.04PC1. The green warped skull corresponds to −0.04PC2 and the orange warped skull corresponds to +0.04PC2. The colours of the warped skulls (i.e. blue, orange, and green) correspond to the colours used in Fig. 6. Arrows show the main shape differences (see text for more details).

Fig. 8

Illustrations of three potential closure pattern sequences of the sagittal suture in sagittal NSC cases as documented in our study. The sagittal suture is divided into three distinct sections: anterior, median, and posterior. Each section is coded as closed (C) or fused (F).