Morphological integration of the skull in craniofacial anomalies.

OBJECTIVES - To understand how surgical interventions impact the organization and internal integration of the major components of the skull, we address the functional and developmental relationships during perinatal development. METHODS - A number of methods for quantifying modularity and integration of morphological data are available. Here, measures derived from three-dimensional computed tomographic (CT) images are used to investigate the statistical relationships among measures of the cranial vault, face and cranial base. First, we establish the pattern of associations among quantitative measures in a sample of children unaffected by a craniofacial anomaly. We statistically compare these normative patterns of cranial integration to those of a sample of children with a facial anomaly (complete unilateral complete cleft lip and palate), and to children with a neurocranial anomaly (isolated sagittal synostosis). Finally, we test whether surgery affects the strength and pattern of associations among measures within the cranial base in the affected children. RESULTS - Our analyses reveal strong internal integration of the cranial base in unaffected children and in our samples of unoperated cleft lip and palate, and sagittal synostosis. Post-operatively, the magnitude of integration of the cranial base is reduced relative to the pre-operative condition in both samples of children with craniofacial anomalies. CONCLUSION - Our results show how the cranial base adjusts to its broader structural context, and provides added support for the developmental and structural integration of cranial base with both cranial vault and face.

The effect of neurocranial surgery on basicranial morphology in isolated sagittal craniosynostosis.

OBJECTIVE: Isolated sagittal craniosynostosis produces a scaphocephalic neurocranium associated with abnormal basicranial morphology, providing additional evidence of the developmental relationship of the neurocranium and basicranium. Corrective surgical procedures vary, but the immediate impact of the surgical procedure is restricted to the neurocranium. This study addresses the secondary effects of neurocranial surgery on the cranial base. DESIGN: Three-dimensional (3-D) computed tomography (CT) scans were obtained for preoperative (n = 25) and postoperative (n = 12) patients with isolated sagittal synostosis. Landmark data from 14 landmarks on and around the cranial base were collected from 3-D CT reconstructions and analyzed using Euclidean distance matrix analysis. Subsamples of age-matched patients were used to identify basicranial differences in pre- and postoperative patients and to compare postoperative growth patterns identified in longitudinal data with preoperative growth patterns characterized in cross-sectional data. RESULTS: Statistically significant differences (p < or = 0.10) were found in the morphology of the cranial base in preoperative and postoperative patients. The relative positions of the landmarks nasion, right asterion, and left asterion are similar in preoperative and postoperative patients. However, the position of these landmarks relative to the cranial base is different in the two groups, being positioned relatively more anteriorly in postoperative patients. In addition, we found that the cranial base angle, on average, neither increases nor decreases in the first postoperative year. These morphological differences are associated with divergent growth trajectories in the operated and unoperated cranial base. CONCLUSION: Regardless of specific procedure, neurocranial surgery in sagittal synostosis patients affects growth patterns of the cranial base. The lack of change in the postoperative cranial base angle suggests that neurocranial surgery alleviates the occipital rotation and decreased cranial base angle described in the sagittal synostosis basicranium.

The Wsh and Ph mutations affect the c-kit expression profile: c-kit misexpression in embryogenesis impairs melanogenesis in Wsh and Ph mutant mice.

The receptor tyrosine kinases (RTKs) c-kit and platelet-derived growth factor receptor alpha chain (PDG-FRa) are encoded at the white spotting (W) and patch (Ph) loci on mouse chromosome 5. While W mutations affect melanogenesis, gametogenesis, and hematopoiesis, the Ph mutation affects melanogenesis and causes early lethality in homozygotes. W-sash (Wsh) is an expression mutation and blocks c-kit expression in certain cell types and enhances c-kit expression in others, including at sites important for early melanogenesis. We have determined the effect of Ph on c-kit expression during embryogenesis in Ph heterozygotes. Immunohistochemical analysis revealed enhanced c-kit expression in several cell types, including sites important for early melanogenesis. We propose that in both Wsh and Ph mutant mice c-kit misexpression affects early melanogenesis and is responsible for the pigment deficiency. Moreover, we have defined the organization of the RTKs in the W/Ph region on chromosome 5 and characterized the Wsh mutation by using pulsed-field gel electrophoresis. Whereas the order of the RTK genes was determined as Pdgfra-c-kit-flk1, analysis of the Wsh mutation revealed that the c-kit and Pdgfra genes are unlinked in Wsh, presumably because of an inversion of a small segment of chromosome 5. The Ph mutation consists of a deletion including Pdgfra and the 3' deletion endpoint of Ph lies between Pdgfra and c-kit. Therefore, positive 5' upstream elements controlling c-kit expression in mast cells and some other cell types are affected by the Wsh mutation and negative elements are affected by both the Wsh and the Ph mutation.

Results of the Senning operation for transposition of the great arteries with intact ventricular septum in neonates.

In spite of an adequate balloon atrial septostomy, some neonates (less than 28 days of age) with transposition of the great arteries and intact ventricular septum (TGA, IVS) remain hypoxemic and acidotic and require operative treatment. Our entire experience with the Senning operation in neonates with TGA, IVS is reviewed. From March 1978 to March 1983 there were 104 infants who underwent the Senning operation for TGA, IVS. Of these, 19 were neonates (18%). The mean age at operation was 12 days (2 to 24) and mean weight was 3.52 kg (3 to 4.38). Two died early (10%) and one died late (5%). The last 16 are alive and well. Causes of early mortality were sepsis and severe obstruction of the superior vena cava. The cause of late mortality was severe pulmonary venous obstruction. Among the 16 survivors, postoperative courses, both early and late, have been remarkably benign. Ten patients have undergone postoperative cardiac catheterization (mean follow up 17 months). Two (12%) had severe pulmonary venous obstruction (one diagnosed by two-dimensional echocardiography), but both were successfully repaired. Atrial shunt was noted in two patients (12%), one of which underwent elective repair. Five infants have dynamic subvalvular pulmonary stenosis of various gradients (9 to 93 mm Hg). One infant has mild tricuspid regurgitation. There are no cases of superior vena caval obstruction or right ventricular dysfunction. Twenty-four hour electrocardiographic monitoring (mean follow-up 25 months) showed predominant normal sinus rhythm in 15 infants and predominant junctional rhythm in one.(ABSTRACT TRUNCATED AT 250 WORDS)