Pediatric Craniosynostosis

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 the Medscape Reference Neurosurgery article Surgery for Craniosynostosis.

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 the list below:

• 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

• Trigonocephaly - Early fusion of the metopic suture

  Frontal view showing a fused and ridged metopic suture on 3-dimensional CT.

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.

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).

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%.[3]

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.[4, 5]

• Craniosynostosis of 1-2 sutures: Cosmetic defect is the primary morbidity.

Sex

Craniosynostosis is equally distributed in both boys and girls.

Age

See the list below:

• 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.

Dependent on cause of craniosynostosis  - if secondary then depends on cause of brain injury. 

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

It may be noticed later when the child exhibits neurodevelopmental delays.

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).

    Positional plagiocephaly. Note anterior position of the ear on the side with occipital flattening.

  • 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.[6]

  • Torticollis is frequently associated with positional molding.

  • Viewed from above, the head shape in positional molding resembles a parallelogram, whereas that in lambdoid craniosynostosis is trapezoid shaped.

    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.

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

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

    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.

• Trigonocephaly

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

    Isolated fusion of the metopic suture. Note that the remaining sutures are open.
    Trigonocephaly. Note the triangular shape of the head.
    Pre- and postoperative photos of metopic synostosis. Note the prominent forehead keel corrected after surgical repair.

  • 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.

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

  Infant with primary craniosynostosis. The specific deformity of the skull is Kleeblattschadel or cloverleaf skull.

• 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.

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]

When careful examination of the cranial shape cannot establish the diagnosis, skull radiographs can be obtained.

Perform skull radiography with anterior-posterior, lateral, and Water views. Prematurely fused sutures are easily identified by the absence of sutures and associated ridging of the suture line. Sutures either are not visible or have evidence of sclerosis.

Cranial CT scan with 3-dimensional reconstruction is not required in most infants. It is sometimes performed when surgery is being considered, or when radiograph results are equivocal.[9]

Nuclear medicine isotope studies are of limited value.

Endocrine evaluation: Order thyroid and parathyroid studies when associated features suggest these diagnoses.

In the past 30 years, a better understanding of the pathophysiology and management of craniosynostosis has developed. Currently, surgery is usually for cranial deformity correction for infants with fusion of 1-2 sutures that results in a misshapen head. For infants with microcephaly (ie, secondary craniosynostosis), surgery usually is not required.

• In patients with microcephaly, investigate the cause of microcephaly.

• Measure head circumference longitudinally and monitor development. Ensure normal brain growth in patients with primary craniosynostosis.

• Carefully monitor signs and symptoms of elevated intracranial pressure.

  • Examine the fundi and alert parents to report persistent vomiting or lethargy promptly.

  • Should elevated intracranial pressure be suspected, an emergent neurosurgical consult would be appropriate.

• To preserve visual function in patients with elevated intracranial pressure, an emergent ophthalmological consult would be appropriate.

• Address the appearance of the skull abnormality.

Surgery is typically indicated for increased intracranial pressure or for correction of the cranial deformity.

Surgery is usually performed in the first year of life.

Do not operate in patients without raised intracranial pressure until considering the following:

• If the shape of the head does not improve by age 2 months, then the abnormality is unlikely to resolve with age. Early referral is helpful if children can be considered for minimally invasive surgery. Infants have a large head relative to body size. Deformity appears more prominent in the young infant and may be less obvious with age.

• Handle minor deformities conservatively. As the child grows and more hair appears, the visible abnormality may decrease.

Consideration for synostosis correction is dependent on the age of presentation and on which sutures have fused prematurely.

• Surgery to correct the cranial or craniofacial deformity is performed in infants aged 3-6 months in the author's practice, although a variety of approaches exist among different surgeons.[10]

• Surgery in younger infants may result in a relatively large loss of blood volume. Accordingly, minimally invasive surgical techniques should be considered. One promising area of investigation is the use of intraoperative tranexamic acid (TXA). A randomized double-blind study published in 2011 concluded that patients undergoing surgical correction of craniosynostosis treated with erythropoietin prior to surgery and TXA during the operation sustained lower volumes of blood loss and received less transfused blood at statistically significant rates than did the control patients.[11]

• A prospective review of 89 children younger than 12 months with sagittal craniosynostosis treated with either endoscopically assisted or open repair found reduced operative times, shorter hospital stays, lower rates of blood transfusion, and excellent outcomes for the patients undergoing endoscopically assisted strip craniectomies followed by helmet therapy. Endoscopic procedures are typically reserved for patients younger than 6 months owing to the difficulties associated with the use of such techniques in older patients with thicker bone.[12]

• Endoscopic metopic synostosis repair is less well defined, but some evidence in the literature suggests that minimally invasive endoscopy-assisted techniques and postoperative cranial molding may be used even in the treatment of infants with multiple-suture nonsyndromic craniosynostosis.[13]

• Surgery in infants older than 8 months may be associated with a slowing of skull growth. Thus, the surgical defect may not be covered adequately by bone growth.

Infants with a defined syndrome causing craniosynostosis should be evaluated early for surgery.

• Results are best when surgery is performed in infants younger than 6 months.

• Patients with associated facial deformities may need a staged surgical approach (performed by a team of multidisciplinary specialists).[14, 15, 16]

Positional molding

No surgery is indicated for posterior plagiocephaly secondary to positional molding.

The vast majority of infants improve with repositioning maneuvers and physical therapy for torticollis.

Some clinicians elect to use molding helmets for severe cases.

Cranial dysmorphology

Often patients present at a later age with nonspecific symptoms of increased intracranial pressure.[10]

A pediatric neurologist should evaluate the cause of the craniosynostosis and differentiate secondary from primary craniosynostosis. The head circumference should be plotted carefully and monitored from birth onward.

A geneticist/dysmorphologist should evaluate for associated syndromes.

A plastic surgeon should evaluate the infant when synostosis is associated with facial deformities.

A neurosurgeon should evaluate a patient with primary craniosynostosis or elevated intracranial pressure.

An endocrinologist should evaluate the patient when appropriate.

Following surgery, patients may require some restriction in activity under the direction of the treating neurosurgeon to avoid head injury.

Following surgery, carefully monitor patients to ensure that the suture does not re-fuse. Continue head circumference measurements. Watch for signs of raised intracranial pressure in infants at risk.

In the immediate postoperative period, complications include hemorrhage.

Patients with primary craniosynostosis must be monitored after surgery. The vast majority of patients with primary, single suture synostosis have little or no morbidity following surgery. One systematic review of neurodevelopmental studies found some evidence that children with single suture synostosis are at increased risk for difficulties in cognitive, language, and motor domains during infancy (both pre- and post-surgery) and childhood.[17]

In secondary craniosynostosis, prognosis is dependent upon underlying etiology.

Patients with syndromic craniosynostosis can have a much more complicated clinical course due to the increased severity of the craniosynostosis and associated problems (e.g., hydrocephalus and airway obstruction). They are also at increased risk of intellectual disability, and social and attention problems.[18] A multidisciplinary approach is important in the management of the complex problems of these patients.

If a patient has a mild head shape deformity, inform parents that the deformity will become less prominent with the appearance of abundant hair and physiological molding.