Multiple theories have been proposed for the etiology of primary craniosynostosis, but the most widely accepted is a primary defect in the mesenchymal layer ossification in the cranial bones.
Secondary craniosynostosis typically results from systemic disorders such as the following:
-
Endocrine - Hyperthyroidism, hypophosphatemia, vitamin D deficiency, renal osteodystrophy, hypercalcemia, and rickets
-
Hematologic disorders that cause bone marrow hyperplasia (eg, sickle cell disease, thalassemia)
-
Inadequate brain growth, including microcephaly and its causes and shunted hydrocephalus
The syndromic causes appear to result from genetic mutations in the fibroblast growth factor pathway, particularly genes involving fibroblast growth factor receptors 2 and 3. A gene locus for single suture craniosynostosis has not been identified. [7]
Other important factors to consider include the following:
-
Differentiating plagiocephaly that results from positional molding (which does not require surgery and is seen frequently) from lambdoid suture fusion is extremely important.
-
The presence of multiple suture fusions strongly suggests a craniofacial syndrome, which frequently requires the diagnostic expertise of a pediatric geneticist.
Craniofacial morphogenesis is highly dependent on the patterning information of emigrant cranial neural crest (CNC) cells. CNC cells give rise to a wide variety of tissues and structures, including skull bones. During skull development, cranial sutures serve as growth centers for skeletogenesis that is mediated through intramembranous ossification. This process differs from endochondral ossification in the appendicular and axial skeletons, where prior formation of cartilage templates is required. Axin2 is highly expressed in CNC cells and developing sutures neural crest (nasal and frontal bones) but not mesoderm (parietal bones). Dependent osteogenesis is particularly sensitive to the loss of Axin2. [8]
-
Diagram of a neonate's skull demonstrating the location of the sutures.
-
Frontal view showing a fused and ridged metopic suture on 3-dimensional CT.
-
CT image demonstrating features of secondary craniosynostosis with cerebral atrophy. Cerebral atrophy is not present in primary craniosynostosis.
-
Positional molding. Note the anterior displacement of the right occiput and of the right frontal region on the same side, which differentiate positional molding from posterior plagiocephaly craniosynostosis.
-
Posterior view of 3-dimensional cranial CT demonstrating early fusion of the lambdoid suture.
-
Isolated fusion of the metopic suture. Note that the remaining sutures are open.
-
Trigonocephaly. Note the triangular shape of the head.
-
Infant with primary craniosynostosis. The specific deformity of the skull is Kleeblattschadel or cloverleaf skull.
-
Skull deformities associated with single suture synostosis.
-
Positional plagiocephaly. Note anterior position of the ear on the side with occipital flattening.
-
Sagittal synostosis and the associated scaphocephaly seen on skull radiograph and 3-dimensional craniofacial CT scan.
-
Sagittal synostosis before and after cranial vault surgery and the associate improvement of scaphocephaly.
-
Unilateral coronal deformity with retrusion of the orbit and harlequin eye deformity. Note the ipsilateral deviation of the nasal radix and the contralateral deviation of the nasal tip.
-
Fusion of coronal sutures bilaterally. Note the increase transverse dimension and retrusion of the orbital rim.
-
Intraoperative view of bilateral coronal synostosis. Note the decreased anterior-posterior dimension, increased transverse width and retruded orbital rim.
-
Pre- and postoperative photos of metopic synostosis. Note the prominent forehead keel corrected after surgical repair.
