AUTHOR INFORMATION	Section 1 of 9
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Author: Raj D Sheth, MD, Professor, Departments of Neurology and Pediatrics, Director of Comprehensive Epilepsy Program, Department of Neurology, University of Wisconsin at Madison Coauthor(s): Bermans J Iskandar, MD, Director, Associate Professor, Departments of Neurological Surgery, Pediatrics, Children's Hospital, University of Wisconsin Hospital and Clinics

Raj D Sheth, MD, is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, American Neurological Association, and Child Neurology Society

Editor(s): James J Riviello, Jr, MD, Professor, Department of Neurology, Director of Epilepsy Program, Division of Epilepsy and Clinical Neurophysiology, Children's Hospital, Harvard University Medical School; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Kenneth J Mack, MD, PhD, Visiting Associate Professor, Department of Neurology, University of Wisconsin at Madison; Associate Professor and Consultant, Department of Neurology, Division of Child and Adolescent Neurology, Mayo Medical School; Selim R Benbadis, MD, Professor of Neurology, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida College of Medicine, Tampa General Hospital; and Nicholas Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants

Disclosure

	INTRODUCTION	Section 2 of 9
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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.

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 (see Image 1).

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

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

Trigonocephaly - Early fusion of the metopic suture (see Image 2).

Secondary craniosynostosis

More frequent than the primary type, secondary craniosynostosis results 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 (see Image 3). Intracranial pressure usually is normal, and surgery seldom is 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 (see Bibliography). This has been demonstrated in coronal craniosynostosis.

Frequency:

• In the US: 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 cosmetic, 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.

• 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.

	CLINICAL	Section 3 of 9
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History:

• Craniosynostosis may be evident at birth or in infancy from craniofacial abnormalities.

• It may become evident later when the child exhibits neurodevelopmental delays.

Physical: Typically, careful examination alone can make the diagnosis.

• Microcephaly usually suggests a secondary craniosynostosis.

• Scaphocephaly

• Premature fusion of the sagittal suture is the most common craniosynostosis, constituting more than half of all cases. It occurs frequently in premature infants.

• The head typically is elongated in the anterior-posterior diameter and shortened in the biparietal diameter. Ridging of the sagittal suture is palpable.

• Anterior plagiocephaly - Premature fusion of 1 coronal suture.

• Brachycephaly

• Premature fusion of both coronal sutures results in increased biparietal diameter. This anomaly is often syndromic. The skull is shorter in the anterior-posterior diameter.

• Because the coronal suture develops in conjunction with the sutures at the base of the skull, unilateral or bilateral mid and upper face hypoplasia may occur. Orbits may be elliptical (ie, Harlequin features), and the supraorbital ridge may not be formed well.

• Consider these features when planning surgery for brachycephaly.

• Posterior plagiocephaly

• The 2 predominant causes of posterior plagiocephaly are craniosynostosis of the lambdoid suture (<2%) or positional molding (vast majority).

• Since the American Academy of Pediatrics recommended that infants sleep on their backs to reduce sudden infant death syndrome (SIDS) incidence, positional molding has been seen with increased frequency.

• Viewed from above, the head shape in positional molding resembles a parallelogram, whereas that in craniosynostosis is trapezoid shaped (see Images 4-5).

• Torticollis frequently is associated with positional molding.

• In positional molding, ear position is more anterior on the side of flattening; in synostosis, ear position is more posterior.

• Frontal bossing is observed ipsilateral to the flattening in positional molding and contralateral in synostosis.

• Trigonocephaly

• Premature fusion of the metopic suture frequently results in pointed forehead (ie, triangular shaped head) (see Images 6-7). The abnormality is usually mild and requires no surgical intervention. Surgery is performed if the abnormality is persistent and severe.

• Oxycephaly (ie, turricephaly) is fusion of all skull sutures and the sutures at the base of the skull.

• Craniosynostosis sometimes is associated with sporadic craniofacial syndromes such as Crouzon, Apert, Chotzen, Pfeiffer, or Carpenter syndromes. In this context, facial features, typically craniofacial abnormalities, suture ridging, and early closure of fontanelles, suggest the diagnosis.

• Kleeblattschädel (ie, cloverleaf skull) results from fusion of all sutures except the metopic and squamosal sutures, giving the head a cloverleaf appearance (see Image 8).

• Intracranial pressure may be elevated in primary multiple suture craniosynostosis, such as cloverleaf skull and the syndromic synostoses. Signs include sun-setting eyes, papilledema, vomiting, and lethargy.

Causes:

• 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 responsible for fibroblast growth factor receptors 2 and 3. A gene locus for single suture craniosynostosis has not been identified.

• Other important factors to consider

• 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.

	DIFFERENTIALS	Section 4 of 9
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Benign Skull Tumors
Hydrocephalus
Mental Retardation
Neural Tube Defects
Syringomyelia
Thyroid Disease
Torticollis

Other Problems to be Considered:

Apert syndrome
Carpenter syndrome
Chotzen syndrome
Crouzon syndrome
Hypercalcemia
Hyperthyroidism
Hypophosphatemia
Kleeblattschädel (cloverleaf skull)
Pfeiffer syndrome
Renal osteodystrophy
Rickets
Vitamin D deficiency