Background
Craniosynostosis consists of premature fusion of 1 or more cranial sutures, often resulting in an abnormal head shape. It may result from a primary defect of ossification (primary craniosynostosis) or, more commonly, from a failure of brain growth (secondary craniosynostosis). Simple craniosynostosis is a term used when only 1 suture fuses prematurely. Complex or compound craniosynostosis is used to describe premature fusion of multiple sutures. When children with craniosynostosis, usually complex, also display other body deformities, this is termed syndromic craniosynostosis.
Also see eMedicine's Neurosurgery article on Craniosynostosis.
Pathophysiology
Normal skull development
Ossification of the cranial vault starts in the central region of each cranial bone and extends outward toward the cranial sutures.
Diagram of a neonate's skull demonstrating the location of the sutures. - The coronal suture separates the 2 frontal bones from the parietal bones.
- The metopic suture separates the frontal bones.
- The sagittal suture separates the 2 parietal bones.
- The lambdoid suture separates the occipital bone from the 2 parietal bones.
- The primary factor that keeps sutures open is ongoing brain growth.
- Normal skull growth occurs perpendicular to each suture.
Primary craniosynostosis [1]
When 1 or more sutures fuse prematurely, skull growth can be restricted perpendicular to the suture. If multiple sutures fuse while the brain is still increasing in size, intracranial pressure can increase.
- Scaphocephaly - Early fusion of the sagittal suture
- Anterior plagiocephaly - Early fusion of 1 coronal suture
- Brachycephaly - Early bilateral coronal suture fusion
- Posterior plagiocephaly - Early closure of 1 lambdoid suture
Secondary craniosynostosis [1]
More frequent than the primary type, secondary craniosynostosis can result from early fusion of sutures due to primary failure of brain growth. Since brain growth drives the bony plates apart at the sutures, a primary lack of brain growth allows premature fusion of all the sutures.
Skull deformities associated with single suture synostosis.
CT image demonstrating features of secondary craniosynostosis with cerebral atrophy. Cerebral atrophy is not present in primary craniosynostosis. Intracranial pressure is usually normal, and surgery is seldom needed. Typically, failure of brain growth results in microcephaly. Premature suture closure does not compromise brain growth and does not require surgery to open sutures.
Intrauterine space constraints may play a role in the premature fusion of sutures in the fetal skull.[2] This has been demonstrated in coronal craniosynostosis. Other secondary causes of craniosynostosis include systemic disorders that affect bone metabolism such as rickets and hypercalcemia (see Causes).
Epidemiology
Frequency
United States
Incidence of craniosynostosis is 0.04-0.1%. Of affected individuals, 2-8% have primary craniosynostosis. The remaining cases are secondary craniosynostosis, which frequently is accompanied by microcephaly. The frequencies of the various types of craniosynostosis are as follows: sagittal 50-58%, coronal 20-29%, metopic 4-10%, and lambdoid 2-4%.
Mortality/Morbidity
Raised intracranial pressure is rare with fusion of a single suture. It can occur in primary craniosynostosis when multiple sutures fuse.
- Primary craniosynostosis: Although the major morbidity is due to the abnormal shape of the skull, intracranial pressure can be elevated. This occurs with a high frequency in multiple suture synostosis and rarely with single suture synostosis.
- Secondary craniosynostosis: Typically no morbidity is noted, except that related to the underlying disorder. The lack of brain growth often is associated with neurodevelopmental delay.[3, 4]
- Craniosynostosis of 1-2 sutures: Cosmetic defect is the primary morbidity.
Sex
Craniosynostosis is equally distributed in both boys and girls.
Age
- Neonatal period: Craniosynostosis is evident at birth when associated with other craniofacial abnormalities.
- Infancy (0-18 mo): Secondary or primary craniosynostosis becomes evident as the child grows.
Jabs EW. Toward understanding the pathogenesis of craniosynostosis through clinical and molecular correlates. Clin Genet. Feb 1998;53(2):79-86. [Medline].
Higginbottom MC, Jones KL, James HE. Intrauterine constraint and craniosynostosis. Neurosurgery. Jan 1980;6(1):39-44. [Medline].
Sheth RD, Schaefer GB, Keller GM, Hobbs GR, Ortiz O, Bodensteiner JB. Size of the corpus callosum in cerebral palsy. J Neuroimaging. Jul 1996;6(3):180-3. [Medline].
Schaefer GB, Sheth RD, Bodensteiner JB. Cerebral dysgenesis. An overview. Neurol Clin. Nov 1994;12(4):773-88. [Medline].
Losee JE, Mason AC. Deformational plagiocephaly: diagnosis, prevention, and treatment. Clin Plast Surg. Jan 2005;32(1):53-64, viii. [Medline].
Robin NH. Molecular genetic advances in understanding craniosynostosis. Plast Reconstr Surg. Mar 1999;103(3):1060-70. [Medline].
Liu B, Yu HM, Hsu W. Craniosynostosis caused by Axin2 deficiency is mediated through distinct functions of beta-catenin in proliferation and differentiation. Dev Biol. Jan 1 2007;301(1):298-308. [Medline]. [Full Text].
Scott JR, Isom CN, Gruss JS, et al. Symptom outcomes following cranial vault expansion for craniosynostosis in children older than 2 years. Plast Reconstr Surg. Jan 2009;123(1):289-97; discussion 298-9. [Medline].
Shah MN, Kane AA, Peterson JD, Woo AS, Naidoo SD, Smyth MD. Endoscopically assisted versus open repair of sagittal craniosynostosis: the St. Louis Children's Hospital experience. J Neurosurg Pediatr. 2011/08;8(2):165-70.
Jimenez DF, Barone CM. Multiple-suture nonsyndromic craniosynostosis: early and effective management using endoscopic techniques. J Neurosurg Pediatr. Mar 2010;5(3):223-31. [Medline].
Keshavarzi S, Hayden MG, Ben-Haim S, Meltzer HS, Cohen SR, Levy ML. Variations of endoscopic and open repair of metopic craniosynostosis. J Craniofac Surg. Sep 2009;20(5):1439-44. [Medline].
Anderson PJ, Netherway DJ, Abbott A, David DJ. Intracranial volume measurement of metopic craniosynostosis. J Craniofac Surg. Nov 2004;15(6):1014-6; discussion 1017-8. [Medline].
Cunningham ML, Heike CL. Evaluation of the infant with an abnormal skull shape. Curr Opin Pediatr. Dec 2007;19(6):645-51. [Medline].
Dadure C, Sauter M, Bringuier S, Bigorre M, Raux O, Rochette A. Intraoperative tranexamic acid reduces blood transfusion in children undergoing craniosynostosis surgery: a randomized double-blind study. Anesthesiology. Apr 2011;114(4):856-61. [Medline].
Dundulis JA, Becker DB, Govier DP, Marsh JL, Kane AA. Coronal ring involvement in patients treated for unilateral coronal craniosynostosis. Plast Reconstr Surg. Dec 2004;114(7):1695-703. [Medline].
Elmslie FV, Reardon W. Craniofacial developmental abnormalities. Curr Opin Neurol. Apr 1998;11(2):103-8. [Medline].
Fernbach SK. Craniosynostosis 1998: concepts and controversies. Pediatr Radiol. Sep 1998;28(9):722-8. [Medline].
Keshavarzi S, Hayden MG, Ben-Haim S, Meltzer HS, Cohen SR, Levy ML. Variations of endoscopic and open repair of metopic craniosynostosis. J Craniofac Surg. Sep 2009;20(5):1439-44. [Medline].
Liptak GS, Serletti JM. Pediatric approach to craniosynostosis. Pediatr Rev. Oct 1998;19(10):352; quiz 359. [Medline].
Miraoui H, Ringe J, Haupl T, Marie PJ. Increased EFG- and PDGFalpha-receptor signaling by mutant FGF-receptor 2 contributes to osteoblast dysfunction in Apert craniosynostosis. Hum Mol Genet. May 1 2010;19(9):1678-89. [Medline].
Sheth RD, Mullett MD, Bodensteiner JB, Hobbs GR. Longitudinal head growth in developmentally normal preterm infants. Arch Pediatr Adolesc Med. Dec 1995;149(12):1358-61. [Medline].
Stelnicki E, Heger I, Brooks CJ, et al. Endoscopic release of unicoronal craniosynostosis. J Craniofac Surg. Jan 2009;20(1):93-7. [Medline].


