Craniosynostosis

• Brachycephaly is derived from the Greek word brachys meaning short.

• Oxycephaly is derived from the Greek word oxys meaning sharp, high, conical head with sharp bossing in the region of the anterior fontanelle.

• Turricephaly is derived from the Latin word turris meaning tall and round head, like a tower.

In the group of nonsyndromic multiple suture synostoses, a variety of types can be included, not all of which have been clearly defined. The most common is bilateral coronal synostosis, which is characterized by brachycephaly. Oxycephaly is a variation of complex, multiple-suture, nonsyndromic form and usually results from a combination of bilateral coronal, sagittal, and, possibly, lambdoid synostosis, resulting in the characteristic head shape. Cloverleaf skull deformity is a separate entity that is characterized by a typical head shape due to bilateral constrictions at the sylvian fissures. Under the term complex multiple suture synostosis, often referred to as pansynostosis, a variety of deformities are included, involving multiple sutures in patterns not conforming to any of the other types. Complex multiple suture synostosis is a mixture of otherwise unclassifiable combinations of affected sutures.

Craniosynostosis also is seen in the context of a variety of syndromes (more than 70). The most common syndromes encountered in clinical practice are Crouzon, Apert, Saethre-Chotzen, and Pfeiffer. These syndromes are all characterized by bilateral coronal synostosis of varying severity, often combined with some degree of sagittal synostosis. The typically observed brachycephaly is due to a shortened anteroposterior diameter of the skull and corresponding enlargement of the bitemporal and biparietal diameter. Other suture involvement can result in oxycephaly, scaphocephaly, and turricephaly. Combinations of all these deformities can be seen in complex cases.

A flat forehead and characteristically low-set ears commonly are seen. Patients, particularly those with Apert syndrome, tend to develop turricephaly, a feature not commonly seen in other syndromic forms. Other extracranial abnormalities commonly are observed as part of the syndromes. In both Crouzon and Apert syndromes, maxillary hypoplasia is present in varying degrees. Syndactyly of hands and feet (acrocephalosyndactyly) is a prominent feature of Apert syndrome. Bilateral ptosis commonly is seen in the context of Saethre-Chotzen syndrome and usually requires surgical treatment. Down slanting of the palpebral fissures is characteristic of Pfeiffer syndrome. In most forms of coronal synostosis, a variable degree of exophthalmos is present

Frequency: The overall incidence of craniosynostosis is estimated as 1:2,000 live births. Crouzon syndrome has an incidence of 1:60,000 live births, Apert syndrome has an incidence of 1:10,0000 live births. Saethre-Chotzen and Pfeiffer syndromes are much less common.

Etiology: The etiology of craniosynostosis is not clear at present, but genetic defects are becoming increasingly recognized. In 1912, Crouzon was the first to recognize an inheritance pattern in the syndrome that he described first as craniofacial dysostosis. He described a family in which the syndrome had been passed on vertically with a pattern similar to autosomal dominance. For several decades little further progress was made. Renewed interest and considerable advances in techniques employed in genetics in the last few years have contributed considerably in breaking new ground on important genetic aspects of craniosynostosis.

In syndromic forms of craniosynostosis, autosomal dominant inheritance clearly has been identified, though a number of patients have spontaneous new mutations. Familial cases are frequent, constituting from 25-46% of the total number of cases, variable for the different syndromes. A complete penetrance has been observed in all inherited cases. In nonsyndromic forms of craniosynostosis, no inheritance pattern has been identified, though familial occurrence has been observed in 4-10% of the patients, variable for the different types of syndrome. In familial cases, variable vertical and horizontal penetrance has been observed.

A major breakthrough in understanding the genetic background of craniosynostosis has been the identification of genetic defects in several syndromes, including the 3 most common ones (ie, Crouzon, Apert, Pfeiffer). The fact that mutations of the group of genes coding for fibroblast growth factor receptor (FGFR) are present in patients with Apert, Crouzon, and Pfeiffer syndromes is now clearly established. These genes, currently 4 are identified, are coding for receptors on the cell surface, which mediate the effects of fibroblast growth factors (FGF). The effects of FGFs are not fully understood, but they are already clearly implicated in important cellular processes such as cell growth, differentiation, migration, and survival. Although the 4 different genes are located in different chromosomes, the receptor proteins they encode for are very similar structurally.

Almost all cases of Apert syndrome are due to 1 of the 2 described mutations of the FGFR2 gene, located on chromosome 7. For Crouzon and Pfeiffer syndromes, the situation is less clear. Additional abnormalities of chromosome 10 have been identified. Currently, 25 mutations have been identified on the FGFR2 gene and implicated in the pathogenesis of Crouzon syndrome. Mutations of both FGFR1 and FGFR2 genes have been described in Pfeiffer syndrome, each corresponding to phenotypes of different clinical severity. No genetic defects have been identified in nonsyndromic forms of craniosynostosis. In the next few years, substantial progress is anticipated in this field, throwing new light on the underlying operative pathophysiological mechanisms in different forms of craniosynostosis. The effector link between the chromosomal defect and the actual premature fusion of the sutures has not been identified so far.

Pathophysiology: Using immunocytochemistry techniques, abnormal osteoblastic activity has been observed in cultures of synostotic bone in which decreased growth rate; decreased alkaline phosphatase production; and increased levels of osteocalcin, platelet-derived growth factor (PDGF), and epidermal growth factor (EGF) have been observed. Histopathological examination of resected sutures has shown new bone formation across the area of the suture in various stages. These stages range from trabecular interdigitation across the fibrous tissue of the suture to frank bony fusion and overproduction, resulting in ridge formation on the site of the affected suture, which is palpable on clinical examination and observed at operation and prominent on the inner table of the skull.

Clinical: Apart from the obvious clinical deformity affecting the face and head, children can have airway problems, especially children with the syndromic form of craniosynostosis. Because of the hypoplastic maxilla, these children have difficulty breathing through their nose and end up breathing through their mouth. At night, these children can have sleep apnea. This affects not only their growth pattern, but also their behavior and speech. Children with raised intracranial pressure (ICP) can complain of chronic headaches, declining school performance, and gradual visual failure. As children grow, abnormal facial appearance has a negative effect on their social integration, with a corresponding effect on personality development.

A small minority of children present late. These children have mild deformity that is unnoticed in the first few months and years of life, and they present aged 4-8 years with symptoms of raised ICP.

One should clearly distinguish children who have a flattened posterior part of the head on one or both sides without having premature fusion of the lambdoid sutures. This condition often is called moulding or positional posterior plagiocephaly and rarely requires surgical treatment. This condition manifests with skull flattening, which usually is not progressive and is considered to be due to the position that the head takes during sleep.

INDICATIONS

No medical treatment for craniosynostosis exists. Indications for surgical treatment in the form of cranial expansion in the first few months of life include progressive facial and cranial deformity, intracranial hypertension, and progressive exophthalmos threatening the eyes.

Later on, children aged 5-10 years may develop recurrent craniostenosis and require repeat operations.

In children with the syndromic form of craniosynostosis, progressive maxillary hypoplasia causes breathing problems and difficulties because of poor dentition apposition. Surgical treatment, in the form of midface advancement, is common in children aged 10-15 years.

RELEVANT ANATOMY AND CONTRAINDICATIONS

Relevant Anatomy: During clinical examination, observing the position of the eyebrows, eyes, nose, cheeks, mandibles, and ears is important. Displacement of one eyebrow downwards may indicate early fusion of the coronal suture on that side. Wide disposition of the eyes, which gives the appearance of a broad root of the nose, may indicate hypertelorism, seen as part of facial clefts. Narrow disposition of the eyes may indicate early fusion of the metopic suture. Proptosis of the eyeballs (exophthalmos) may indicate shallow orbits, which are seen in the presence of bilateral coronal synostosis. Curvature of the nose (facial scoliosis) is seen in unilateral coronal synostosis and syndromes that produce mandibular hypoplasia. Atrophic cheeks are seen in syndromes that cause midface hypoplasia. This often is accompanied with oral malocclusion because the upper jaw is recessed and cannot appose the lower jaw, as in healthy individuals.

Unilateral or bilateral atrophic mandible is seen in the context of various forms of hemifacial microsomia. Anterior and downward displacement of the ears may indicate a skull base deformity, which usually coexists as part of premature suture closure.

Of surgical importance is the configuration of the bony skeleton of the orbits, the anterior fossa floor and the temporal regions. These are the sites where commonly osteotomies are performed during corrective surgery. Useful anatomical information is extracted from 3-Dimensional CT scans on bone windows. The surgeon can appreciate the morphology in the sites of interest, and formulate a plan on how much he needs to advance the supraorbital bar of the frontal bone and correct the orbits. Similarly, on deformities that affect the posterior part of the skull, he can appreciate the relationship of the deformity to the sagittal sinus and the foramen magnum, and formulate a surgical plan accordingly.

Contraindications: In severe cases, other congenital problems, such as heart or lung disorders, may represent contraindication to surgical treatment if the child is not fit to undergo general anesthesia. In the rare occasions in which a blood dyscrasia is present, this will need appropriate preoperative, intraoperative, and postoperative management to avoid excess blood loss. In rare severe cases where multiple other congenital deformities exists, the life expectancy may be poor, and in such cases surgeons may feel that surgical correction of craniosynostosis may not be appropriate.

WORKUP

Lab Studies:

• No particular laboratory tests are specific to craniosynostosis. All patients heading for surgical treatment have their hemoglobin and electrolytes checked to make sure they are within the normal range so they can be submitted to general anesthesia.

• Plain radiographs are easily obtainable and demonstrate osseous anatomy well. Plain radiographs are used extensively in patients with craniosynostosis. They are useful in identifying the prematurely fused sutures; demonstrating the overall morphology of the cranium; identifying the presence of localized problems, eg, constricting bony bands impairing growth; and identifying the presence of generalized problems, eg, the copper-beaten appearance, indicating intracranial hypertension

• Serial radiographs in borderline cases or in patients with suspected recurrent stenosis after surgical treatment are used to assess evolution of the deformity.

• The use of standardized views allows measurement of cephalometric features and serial follow-up. Several indices have been devised and used for comparisons. The most popular index has been the cranial index described by Cronqvist. A considerable body of scientific work exists exploring the value of cephalometric studies on the growth of the head and face in a normal state and in craniosynostosis in which the effect of corrective surgery can be monitored.

• Growth of the cranial vault and maturation of the facial skeleton have been demonstrated to occur at different ages. Also, different types of craniosynostosis have been shown to have differential growth of the skull vault and skull base, caused by differential pathological involvement of the sutures of the anterior and posterior skull base, supporting earlier views that the sutures of the skull base are implicated in the morphogenesis of some types of craniosynostosis.

• In the case of positional posterior plagiocephaly, the plain skull radiographs show normal lambdoid sutures.

• The introduction of CT scan provided a more detailed way of visualizing intracranial pathology. Visualization of detailed anatomy of the calvarium and the brain parenchyma became possible. The fused sutures clearly are identified, the abnormal contour of the skull is better appreciated, and the associated cerebral abnormalities, such as hydrocephalus, are demonstrated  The relationship of soft and hard tissues of the craniofacial skeleton can be studied in detail. The skull base in particular, poorly visualized with plain radiographs, is well imaged with CT scan.

• The principle of cephalometry also has been applied to CT scans. Using various, fixed, bony landmarks, the growth of various parts of the skull, in particular the skull base and orbital complex, have been investigated in the normal state and in craniosynostosis and the effect of corrective surgery quantified. Skull base growth has been demonstrated to be different in the various types of craniosynostosis, depending on the involved prematurely fused suture, morphologically more abnormal for single-suture and nonsyndromic bilateral coronal synostoses than syndromic forms. In syndromic craniosynostosis, the skull has been shown to be wider at the level of the coronal sutures and shorter at the midsagittal plane. The orbits are smaller, wider spaced, and more protruding, a numerical confirmation of the clinical observations of brachycephaly and exophthalmos.

• The effect of corrective surgery has been documented. The morphology of the cranial base has been shown to be normalized following cranial expansion surgery in the single-suture and nonsyndromic bilateral coronal synostoses. Also, in Apert syndrome following successful surgery, persistent brachycephalic features still are demonstrated in the form of wide intercoronal distance and short skull anteroposterior length, while the vault remains tall, even though the shape of the skull has changed. Following surgery, the brain has been shown to be slow to expand; the new space is occupied mostly by cerebrospinal fluid (CSF), and often persistent empty extradural space at the site of frontal advancement exists in the early postoperative period.

• The development of 3DCT added a new dimension to imaging of craniosynostosis. The technique is particularly appropriate for bony structures, and can demonstrate detailed skull anatomy with a perspective view, which is particularly helpful in understanding complex craniofacial deformities. The skull vault and base deformities can be appreciated in the 3-dimensional space ( Features such as shallow anterior fossa, deformed dystopic orbits, abnormal calvarial contour, and asymmetric cranial base can all be visualized realistically. This imaging modality has proven valuable in operative planning and assessment of the results of surgery.

• MRI offers improved definition of intracranial soft-tissue structures compared to CT scan. Only recently, attention extended beyond the skull bones towards their contents. A wealth of information gradually is emerging. A high incidence of acquired hindbrain herniation has already been shown to occur in children with syndromic craniosynostosis, particularly children with Crouzon and Apert syndrome. Hindbrain herniation has been seen in as many as 70% of these patients  Hindbrain herniation has been demonstrated to be caused by early closure of the lambdoid sutures. Other abnormalities assessed well by MRI are hydrocephalus and cerebral developmental defects, such as myelination defects and deformities of airway pathways, associated with the maxillary hypoplasia seen in Crouzon and Apert syndromes.

Several variations of this technique have been described, differing mainly on the alternative possibilities of fixation of the lateral ends of the supraorbital bar on the adjacent temporal or zygomatic bones. The 2 most frequently used techniques are the "floating forehead" and the "tongue-in-groove" . The former completely disconnects the supraorbital bar and forehead from the temporal bones, aiming to allow complete freedom of growth of the forehead from the skull base. The latter purposely attaches the supraorbital bars on to the adjacent temporal bones with internal fixation, aiming to maintain synchrony of growth between the realigned forehead and skull base. Although great claims have been made from proponents of both techniques, the clinical results are very comparable.

For different types of craniosynostosis, appropriate modifications on the main technique of frontoorbital advancement are made. In metopic synostosis, the ridge of the prematurely fused suture is excised and the forehead is reconstructed with suitably designed frontal flaps and supraorbital bars. In unilateral coronal synostosis, earlier views favored unilateral frontal advancement. Although only one coronal suture is prematurely fused, in fact the deformity is bilateral because the normal side is attempting to compensate, and bilateral forehead correction usually is necessary.

All variations of frontoorbital advancement usually achieve satisfactory cosmetic results, with good forehead appearance and satisfactory cover of the orbits . A problem often encountered and difficult to correct is persistent narrowing in the temporal regions, observed after any type of frontoorbital advancement. In addition, abnormalities relating to abnormal skull growth, such as turricephaly, brachycephaly, low-set ears, and orbital dystopia, usually persist after successful surgery.

While frontoorbital advancement provides satisfactory correction of exorbitism and cosmetic improvement of forehead appearance, the principle of frontoorbital advancement does not seem to have any scientific basis. Many studies have indicated that this surgical technique is overcorrecting head volume, producing supranormal head volumes. This explains observations of a high incidence of frontal extradural collections at the site of the advancement after a successful surgery. Similarly, following successful correction of unilateral coronal synostosis, the previously compressed brain does not reexpand, and CSF occupies the newly created space instead. In the absence of another better alternative, frontoorbital advancement will continue to prevail, but it appears to have a cosmetic nature in most cases, excluding children with threatening exorbitism.

In a small selected group of patients for whom, despite classic syndromic appearances, the predominant problem found on careful appraisal of radiologic images is constriction of the posterior aspect of the skull. Recent attention to the posterior skull has demonstrated that posterior skull release can produce satisfactory results, often obviating the need for frontal advancement.

Syndromic patients with midface hypoplasia may require midface advancement. Midface advancement can be achieved either by a Le Fort III osteotomy and advancement in 1 operation or by midface distraction. The latter is gaining popularity because, even though it confines the patient to wear an external frame for several weeks, it appears to achieve a better long-lasting result.

Whenever the issue of possible intracranial hypertension arises, ICP monitoring usually is performed over 24 hours using an invasive bolt. Using an invasive bolt requires a small operation. In some units, routine measurement of ICP is performed in all syndromic cases, though this is not a universal policy.

Preoperative details: Children with significant midface deformity should be assessed by an anesthetist well before surgery because intubation may be a problem, and in extreme cases, tracheostomy may be required postoperatively.

Postoperative details: Postoperative imaging is used to demonstrate the new arrangement of the bony architecture of the cranial and facial skeleton. Radiographs obtained early in the postoperative period can be used as reference for further assessment. The rate of reossification can be assessed in the regions were dura was left uncovered by calvarium as a result of the advancement.

Evolution of radiological appearances can be particularly useful if the issue of recurrent deformity arises. While some loss of the advancement is expected in the first few years after operation, other features are seen as well in cases of recurrent craniostenosis, such as localized or generalized copper beating and sclerotic hyperdense bands of bone in the calvarium, representing recurrent synostosis.

Recently, the issue of the migration of fixation screws, plates, and wires has gained increasing attention. As the child grows, the skull bones continuously remodel according to natural forces. As a result, the screws used to stabilize the mobilized segment end up buried in the skull or even in the intracranial cavity. Postoperative CT scan is particularly helpful in monitoring that situation. Although the clinical significance is not known, identification and follow-up of the problem provides an opportunity for appropriate action to be taken. The recent development of bioabsorbable plates and screws may well eradicate the problem of migration.

Follow-up care: Typically, each patient has early postoperative plain radiographs, a CT scan in the first few months after operation, and in syndromic cases, MRI scans at yearly intervals to exclude development of hindbrain hernia. In patients with maxillary hypoplasia, yearly plain radiographs may be needed to assess the progress of the deformity when the issue of possible midface advancement is considered.

COMPLICATIONS

Complications after craniofacial surgery are rare. Hypovolemic shock can occur if significant intraoperative blood loss has not been replaced timely. Intraoperative dural tears, which remain unrecognized, can cause postoperative CSF leaks and resultant infection. Epidural or subdural hematoma can occur due to surgical trauma. Almost all patients develop facial swelling postoperatively, more prominent around the eyes, which rarely causes problems. Wound infections generally are rare, even after midface procedures, which, by necessity, involve operating in the oral cavity. The frequency of these complications is less than 10%.

ICP bolt insertion has a recognized small complication rate (2%), including intracranial hemorrhage and infection.

OUTCOME AND PROGNOSIS

Most patients respond very well to surgical treatment of craniosynostosis. The improvement in head shape is appreciated almost immediately after the operation. After the first few weeks, the facial swelling and orbital bruising settles, and most parents are happy with the cosmetic result.

In a small minority of patients, the deformity recurs after a few years and requires reoperation.

Children with syndromic deformities require careful follow-up into adulthood because they may develop recurrent stenosis and/or raised ICP from other causes (eg, hydrocephalus, hindbrain hernia), and they may need surgery on their midface.

Children with syndromic forms of craniosynostosis (Crouzon, Apert) can be affected by a variable degree of developmental delay, which becomes apparent later on in life.

FUTURE AND CONTROVERSIES

With the increasing awareness of pediatricians and family doctors, craniosynostosis usually is diagnosed in the first few months of life. Sagittal synostosis is effectively treated with strip craniectomy when performed in the first 3 months of life. For craniosynostosis affecting the coronal sutures, considerable debate still exists regarding the timing of cranial expansion surgery. Views vary widely, and some physicians prefer to perform surgery soon after birth, while others defer surgery until the child is aged 12 months.

Proponents of early surgery believe that cranial expansion at an early age is taking advantage of the push that the growing brain applies to the skull, while minimizing the risk of mental impairment due to restricted brain growth by relieving intracranial hypertension early. This belief stems from the view that the skull grows in response to the growth of the brain, which is regarded as the main driving force of head growth.

A significant problem associated with early corrective surgery is a higher risk of recurrent deformity. In most series published from centres performing frontal advancement in the first few months of life, a high reoperation rate is reported. This high rate could be explained by the observation that in the first months of life craniosynostosis is still active; therefore, the effect of cranial expansion is less likely to be retained.

This hypothesis is reflected by the observation that frontoorbital advancement performed at such an early age needs to include some overcorrection in order to achieve good late results. Often, several operations are required in the first few years of life to achieve satisfactory results. Although this may be socially acceptable among circles where the quest for perfect shape prevails, these procedures constitute major surgery with a small but appreciable risk of morbidity and mortality.

All the published evidence in favor of early surgery is colored by prejudice and preference of the reporting authors, and no comparative study of early versus late surgery has ever been conducted. Some indirect evidence in favor of early surgery has been reported based on measurements of ICP and intelligence quotient (IQ). These reports are based on retrospective observations, utilize very crude measures of outcome, and have not conclusively analyzed the effect of the different variables involved in psychomotor development; therefore, they cannot be regarded as definitive evidence.

Proponents of late surgery believe that delaying surgery until most of the skull growth has been completed reduces the risk for recurrent deformity. This view is supported by an observed lower reoperation rate in children and infants who were initially treated when older than 9 months. Critics of delayed surgical treatment point out that the final results of such policies often are not as attractive cosmetically. In addition, the delay in surgical decompression of the brain may impair the mental and psychological outcome of these children. This may be particularly important because a high proportion of patients with syndromic forms are likely to have intracranial hypertension.

Although significant indirect evidence indicates that late surgery (occurring in children older than 12 mo) in all types of craniosynostosis, even scaphocephaly, is associated with poor psychomotor development, the issue is complicated by many interrelated parameters, and no conclusive evidence has been produced. Conversely, in patients with sagittal synostosis, a 30% incidence of speech and language developmental delay has been observed, which cannot be explained on the basis of sustained intracranial hypertension because the condition is associated with a low incidence of intracranial hypertension and all children are operated on early in life.

In attempts to define the optimum surgical time, a few studies have reported measurements of skull volumes in children with craniosynostosis. Some studies concluded that intracranial volume in children with craniosynostosis is within normal limits and that children with Apert syndrome tend to have higher than normal intracranial volumes.

Two studies attempted to correlate skull volume in craniosynostosis with ICP. No correlation between ICP and intracranial volume has been identified. Intracranial hypertension can exist in the presence of normal head volume. A recent study that analyzed the change of intracranial volume with age showed that patients with craniosynostosis start their life with an intracranial volume smaller than their healthy peers. By the time the infants are aged 6-9 months, their intracranial volume has reached normal levels and continues to grow normally. If any restriction of brain growth by slow skull growth occurs, it is only operative in the first 6 months of life. After the infantis older than 6 months, the effect of craniosynostosis becomes exhausted or burnt out.

The maximum constrictive effect of craniosynostosis appears to occur at birth when the difference in intracranial volume between healthy neonates and neonates with craniosynostosis is maximal. After birth, the constrictive effect gradually declines during the first few months and stops being active in infants aged 6-9 months. Therefore, this would appear to be the optimal time for definitive corrective surgery because any alteration made on the cranial skeleton is likely to remain. Such a policy would not apply to patients with overriding reasons dictating early operation, such as severe intracranial hypertension or exorbitism.

A major factor implicated in the timing of surgery for craniosynostosis is the development of intracranial hypertension. No reliable indirect indicators of intracranial hypertension exist. Papilloedema rarely is seen in children with craniosynostosis, even in the presence of intracranial hypertension. Among patients with verified intracranial hypertension, only a small proportion (16-25%) have papilloedema. On the other hand, late presentation of craniosynostosis can lead to irrecoverable optic atrophy and visual failure due to sustained intracranial hypertension. The presence of copper-beaten skull on the plain skull radiograph does not correlate well with the level of ICP.

No satisfactory noninvasive technique of measuring ICP exists. Previous work carried out demonstrated the relative value of transcranial Doppler. The practicalities of performing such an examination are so complex that they prevent the routine use of Doppler in very young patients.

Recent work has indicated that the tympanic membrane could be used for ICP measurement. The current techniques of measuring ICP are invasive, employing subdural or intracerebral transducers and having a small but appreciable complication rate.

A significant proportion of patients with craniosynostosis, (25-35%) are likely to have intracranial hypertension. The incidence of intracranial hypertension varies among different types of craniosynostosis and is higher in syndromic forms. As many as 60% of patients with Crouzon syndrome and 45% of patients with Apert syndrome have intracranial hypertension. Percentages vary for other forms of craniosynostosis. Of patients with nonsyndromic coronal synostosis, 30% have intracranial hypertension. Of patients with sagittal synostosis, 18% have intracranial hypertension, and of patients with unilateral coronal synostosis, 12% have intracranial hypertension.

ICP has been found at higher rates in children presenting with craniosynostosis when older than 12 months. This may imply a rise of ICP with age in patients with craniosynostosis. Children with late presenting craniosynostosis constitute a rare and poorly studied group in which different considerations may apply with respect to head growth. In addition, intracranial hypertension has been reported to be able to persist despite cranial expansion surgery. This raises the question whether poor psychomotor development and the high incidence of intracranial hypertension seen in patients with syndromic craniosynostosis could be due to a genetically predetermined tendency for adverse brain development.

The cause and mechanism of intracranial hypertension in children with craniosynostosis is not well understood. Intracranial hypertension may be due to other causes and/or unrelated to skull constriction, such as abnormal venous drainage in the skull base causing venous hypertension, hydrocephalus, and obstruction of the upper airways.