Pathology of Nonsyndromic Craniosynostosis in Children

Pathophysiology

• 1851 – Virchow’s principle of head growth: Current knowledge about head shape is based on Virchow’s monumental paper from 1851. In retrospect, his article he described the various head shapes of microcephalic children. However, his observations still give us insight into growth about the suture.
• Growth perpendicular to suture: The skull appears to grow perpendicular to the suture line. This determination is based on the retrospective evaluation of patients with craniosynostosis and resultant head shape.

Sagittal synostosis

• Scaphocephaly: The lack of growth along the midline suture permits the continued growth of the skull perpendicular to the coronal and lambdoid sutures. This gives the head the long, narrow appearance with the anterior and posterior bossing.

Coronal synostosis

• Anterior plagiocephaly: The lack of growth at one coronal suture directly causes the flat forehead on that side. Thereby, the ipsilateral ear will be “pulled” forward to the closed suture, and the lateral orbit will be “pulled” toward that suture. This gives the harlequin eye appearance on radiographs. However, there is growth at the open sutures, allowing a prominence to develop in all perpendicular directions to these open sutures.

Metopic synostosis

• Trigonocephaly: There is no growth perpendicular to the midline suture, thereby causing the triangular shape to the forehead. Posterior parietal regions are full.

Lambdoidal synostosis

• Posterior plagiocephaly: There is no growth perpendicular to the involved suture. That suture will be flat. Growth around the suture is involved, thereby “pulling” the ipsilateral ear back. There is perpendicular and more apparent growth to the contralateral lambdoid and parietal regions and ipsilateral mastoid region.

Molecular/Genetic Pathology

Sagittal synostosis

• Sporadic: Most cases of nonsyndromic single suture synostosis are sporadic with no previous family history (1).

Coronal synostosis

• FGGR-3 mutations: FGGR-3 mutation is observed in 12% of sporadic cases and up to 73% of familial cases. Many are bicoronal, and most are female (40).

Metopic synostosis

• 25% associated with other anomalies: Metopic synostosis has a high association (28%) with other intra-and extracranial congenital anomalies and syndromes (4, 48).