Introduction
The term craniosynostosis refers to the premature fusion of one or multiple cranial sutures. Craniosynostosis is commonly present at birth but is not always noticeable, especially when mild. It certainly manifests as a clinical deformity in the first few months of life. Apart from the obvious cosmetic facial and cranial deformity, early closure of sutures can cause intracranial hypertension and adversely affect development in some patients.
Skull shape in various forms of craniosynostosis. A is sagittal synostosis, B is metopic synostosis, C is unilateral coronal synostosis, and D is bilateral coronal synostosis.
History of the Procedure
Otto recognized the first premature closure of sutures as a discrete clinical entity in 1830 and coined the term craniosynostosis.1 Stahl and Hyrtl noticed that premature closure of the cranial vault sutures leads to an abnormal skull shape. In 1851, Virchow described how skull growth is restricted to a plane perpendicular to the affected, prematurely fused suture and is enhanced in a plane parallel to it.2 For almost a century, this has been the main theory explaining the observed cranial deformities. Virchow was the first person to classify the different types of skull deformity seen in persons with craniosynostosis and introduced the morphological descriptive terms still in use today.
Observations from Crouzon3 and Apert4,5 from 1910 to the 1920s led to the realization that in some cases, cranial and facial deformity was only part of a wider complex of deformities, constituting the respectively named syndromes (Crouzon and Apert syndromes) that included abnormal development of the facial skeleton (Crouzon syndrome) and associated limb deformities (Apert syndrome).
In the 1950s, Moss pointed out that removal of the affected suture does not alter the abnormal skull growth and demonstrated skull base abnormalities in patients with sagittal and bicoronal synostosis.6 He concluded that the main mechanism leading to cranial deformity in most types of craniosynostosis was abnormal growth at the level of the skull base, rather than the actual fused sutures, and that skull growth follows brain development.
His views changed the entire concept of surgical treatment of craniosynostosis, moving it from excision of affected sutures with linear craniectomies to complex cranial expansion procedures, addressing the restriction at the skull base. Tessier pioneered the latter procedures in the early 1960s and is regarded as the father of modern craniofacial surgery.7 He was the first to attempt major surgical procedures on the craniofacial skeleton. Initially, he performed surgical procedures as part of reconstructive surgery after trauma, but later, he attempted surgical procedures on patients with craniosynostosis. Starting with adults and extending his techniques to children, he attempted various procedures, including fronto-orbital and midface advancements, both separately and as monobloc procedures.
The introduction of computed tomography (CT) in the late 1970s offered a new tool for visualizing the anatomical deformities that is more accurate than plain radiographs. The introduction of the CT scan gave rise to a new perspective into skull growth and resulted in the concept of 3-dimensional skull growth and deformity in disease states. Although Virchow initially focused his attention on the skull vault and Moss later focused his attention on the skull base in a mutually exclusive manner, the introduction of CT scans signaled a new era and effected an amalgamation of their views. Serial visualization of the evolving deformity and assessment of the effects of surgery using CT scan images offered clinicians the opportunity to monitor the effect of craniosynostosis on skull growth. Subsequent technological improvements led to 3-dimensional reconstruction of CT scan images, which produced a realistic 3-dimensional visual impression of the skull and improved understanding of the condition.
Problem
Two ways of describing the types of craniosynostosis exist, according to the clinical deformity itself or the affected sutures. Virchow, influenced by then prevailing anthropological concepts, developed the former. The latter was developed by Ingraham and Matson and is based mainly on radiological evidence of fused sutures. To a large extent, correspondence between the 2 nomenclatures exists, better appreciated in single suture forms of craniosynostosis. Image 1 shows in diagrammatic fashion the main deformities in the most common types of craniosynostosis.
Skull shape in various forms of craniosynostosis. A is sagittal synostosis, B is metopic synostosis, C is unilateral coronal synostosis, and D is bilateral coronal synostosis.
Scaphocephaly is derived from the Greek words scaphos, meaning boat, and kephali, meaning head. Scaphocephaly corresponds to sagittal synostosis.
Plagiocephaly is derived from the Greek word plagios, meaning oblique or sloping, and corresponds to unilateral coronal synostosis. The term posterior plagiocephaly corresponds to lambdoid synostosis.
Trigonocephaly is derived from the Greek word trigonos, meaning triangular, and corresponds to metopic synostosis.
The terms brachycephaly, oxycephaly, and turricephaly are used for various forms of synostosis affecting both coronal sutures in the former or in combination with the sagittal and sphenofrontal sutures in the latter forms, usually encountered in syndromic types. Brachycephaly is derived from the Greek word brachys, meaning short.
Oxycephaly is derived from the Greek word oxys, meaning sharp, and is a high, conical head with sharp bossing in the region of the anterior fontanelle.
Turricephaly is derived from the Latin word turris, meaning tall, and is a round head, like a tower.
Cloverleaf skull deformity, triphyllocephaly (derived from the Greek word triphyllos, meaning trefoil, with 3 leaves), is a specific type of multiple suture synostosis characterized by a head shaped like a cloverleaf or trefoil, which is a trilobular head with pronounced constrictions in both sylvian fissures and bulging temporal regions.
German terms occasionally appear in the literature. Turmschãdel means turricephaly, and kleeblattschãdel means cloverleaf skull deformity. Classification into nonsyndromic and syndromic forms is commonly used in clinical practice. Nonsyndromic forms of craniosynostosis include single-suture and multiple-suture synostosis not associated with any other syndromic features. Of the single-suture craniosynostoses, the most common in order of incidence are sagittal, unilateral coronal, and metopic synostosis, constituting, respectively, 35%, 15%, and 5% of all cases of craniosynostosis.
In the group of nonsyndromic multiple-suture synostoses, various 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 the 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 characterized by a typical head shape due to bilateral constrictions at the sylvian fissures. Complex multiple-suture synostosis, often referred to as pansynostosis, includes various deformities 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 is also seen in the context of various syndromes (>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 are common. Patients, particularly those with Apert syndrome, tend to develop turricephaly (see Image 2), a feature not commonly seen in persons with other syndromic forms. Other extracranial abnormalities are commonly observed as part of the syndromes. In those with Crouzon or Apert syndromes, maxillary hypoplasia is present in varying degrees. Syndactyly of hands and feet (acrocephalosyndactyly) is a prominent feature of Apert syndrome. Bilateral ptosis is common 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.
Girl aged 11 months with Apert syndrome, with brachycephaly and turricephaly. The low-set ears and flat eyebrows are indicative of the deformed skull base. The maxillary hypoplasia is seen clearly, even at this age, and will become more obvious later on in life.
Frequency
The overall incidence of craniosynostosis is estimated as 1 case in 2000 live births. Crouzon syndrome has an incidence of 1 case in 60,000 live births. Apert syndrome has an incidence of 1 case in 10,000 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.3 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 the techniques used in studying genetics in the last few years have contributed considerably to advancing knowledge on important genetic aspects of craniosynostosis.
Autosomal dominant inheritance has been clearly identified in syndromic forms of craniosynostosis, although 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. Complete penetrance has been observed in all inherited cases. No inheritance pattern has been identified for nonsyndromic forms of craniosynostosis, although a familial occurrence has been observed in 4-10% of the patients, variable for the different types of syndromes. 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: Crouzon, Apert, and Pfeiffer. The presence of mutations in the group of genes coding for fibroblast growth factor receptor (FGFR) in patients with Apert, Crouzon, and Pfeiffer syndromes is now clearly established. These genes (currently, 4 are identified) code 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 7.8 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, adding to the current knowledge on the underlying operative pathophysiological mechanisms for different forms of craniosynostosis. As yet, the effector link between the chromosomal defect and the actual premature fusion of the sutures has not been identified.
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, and epidermal growth factor have been observed. Histopathological examination of resected sutures has shown various stages of new bone formation across the area of the suture. 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 upon clinical examination and observed at operation and is prominent on the inner table of the skull.
Presentation
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 experience 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 when 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 is often called moulding or positional posterior plagiocephaly and rarely requires surgical treatment. This condition manifests with skull flattening, which is usually not progressive and is considered to be due to the position the head takes during sleep.
Indications
No medical treatment exists for craniosynostosis. 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 may 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
During the 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 is often accompanied by 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 at which osteotomies are commonly performed during corrective surgery. Useful anatomical information is extracted from 3-dimensional CT (3D-CT) scan images of bone windows. The surgeon can appreciate the morphology in the sites of interest and can formulate a plan for how far the supraorbital bar of the frontal bone must be advanced to correct the orbits. Similarly, with deformities that affect the posterior part of the skull, the surgeon can appreciate the relationship of the deformity to the sagittal sinus and the foramen magnum and can 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 requires appropriate preoperative, intraoperative, and postoperative management to avoid excess blood loss. In rare severe cases in which multiple other congenital deformities exist, the life expectancy may be poor, and, in such cases, surgeons may believe that surgical correction of craniosynostosis may not be appropriate.
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Further Reading
Clinical guideline
Prevention and management of positional skull deformities in infants.
American Academy of Pediatrics - Medical Specialty Society. 2003 Jul. 4 pages. NGC:003254
Clinical trials
Endoscopic Treatment for Isolated, Single Suture Craniosynostosis
Osteogenic Profiling of Tissue From Children With Craniosynostosis
Clinical Study of Muenke Syndrome (FGFR3-Related Craniosynostosis)
Tranexamic Acid for Craniofacial Surgery
Related eMedicine topics
Apert Syndrome
Congenital, Synostoses
Craniosynostosis Management
Craniosynostosis (Neurology)
Craniosynostosis (Radiology)
Crouzon Syndrome
Keywords
craniosynostosis, craniostenosis, craniofacial dysostosis, craniofacial defect, craniofacial surgery, cranial sutures, cosmetic facial deformity, cranial deformity, cranial malformation, intracranial hypertension, abnormal skull shape, abnormal head shape, skull growth, Crouzon syndrome, Apert syndrome, Crouzon's syndrome, Apert's syndrome, scaphocephaly, sagittal synostosis, plagiocephaly, unilateral coronal synostosis, posterior plagiocephaly, lambdoid synostosis, trigonocephaly, metopic synostosis, brachycephaly, oxycephaly, turricephaly, cloverleaf skull deformity, triphyllocephaly, pansynostosis, Saethre-Chotzen syndrome, Pfeiffer syndrome, Pfeiffer's syndrome, cranial expansion, mid-face advancement, midface advancement
