Surgery for Craniosynostosis
- Author: John A Jane, Jr, MD; Chief Editor: Brian H Kopell, MD more...
The term craniosynostosis refers to premature fusion of one or more of the 6 cranial sutures, the midline metopic and sagittal sutures, and each bilateral coronal and lambdoid sutures. It usually manifests as an observable deformity within the first few months of life. Craniosynostosis can be present at birth but can be missed if mild. The premature fusion of sutures can produce intracranial hypertension, which may lead to abnormal neurocognitive development in affected children. The image below depicts unilateral coronal craniosynostosis.
History of the Procedure
Hippocrates (c. 460-370 BCE) described skull and cranial suture morphology in detail. Heroditus (c. 484-425 BCE) described a skull without sutures, composed of unique bone. Galen of Pergamon (130-200 CE) introduced the term oxycephaly and the concept of craniosynostosis. While Vesalius (1514-1564) illustrated the absence of various sutures, the skulls were not depicted in an appropriate shape with regard to the fused suture. Later, in 1830, Wilhelm Otto recognized premature closure as the primary cause of craniosynostosis. Stahl and Hyrtl noted that premature closure of 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. 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. In 1890, Odilon Lannelongue (1840-1911) introduced a linear craniectomy in order to allow for normal brain growth.
Observations from Crouzon and Apert[8, 9] 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. 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. He was the first to attempt major craniofacial surgical procedures. 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.
In 1978 Jane and Park pioneered the pi procedure for correction of sagittal synostosis. The procedure was named for its resemblance to the Greek letter pi. In 1996 Jane described the reverse pi procedure to treat posterior fusion of the sagittal suture, also known as an occipital knob. More recently, Engel used a modified pi procedure based on Jane's for improved cephalic index.
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 scans offered clinicians the opportunity to monitor the effect of craniosynostosis on skull growth. Subsequent technological improvements led to 3-dimensional reconstruction of CT scans, which produced a realistic 3-dimensional visual impression of the skull and improved understanding of the condition.[15, 16, 17, 18, 19]
The 2 ways of describing the types of craniosynostosis are (1) according to the clinical deformity itself and (2) according to 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. The illustrations below demonstrate the main deformities in the most common types of craniosynostosis.
The rules for growth with regard to the fused sutures are indicated by the arrows in the illustrations below. Closure of a single suture does not only cause restriction of growth perpendicular to the fused suture, but it also causes compensatory growth at adjacent sutures. If the adjacent suture is parallel to the fused suture, the compensatory growth occurs equally in both directions. If the suture is perpendicular to the fused suture, the compensatory growth occurs away from the fused suture. Therefore, even single-suture closure affects the growth of the entire skull. It has also been recognized that the skull base suture system, although not amenable to surgery, is important in the development of craniosynostosis. The coronal ring is the most important suture system affecting the base, followed by spheno-occipital synchondrosis.
Trigonocephaly corresponds to metopic synostosis and is derived from the Greek word trigonos, meaning triangular.
Scaphocephaly corresponds to sagittal synostosis and is derived from the Greek words scaphos, meaning boat, and kephali, meaning head.
Plagiocephaly corresponds to unilateral coronal synostosis and is derived from the Greek word plagios, meaning oblique or sloping.
The term posterior plagiocephaly corresponds to lambdoid synostosis.
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. These synostoses are usually encountered in syndromic patients.
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 used to describe a round head shaped like a tower and is derived from the Latin word turris, meaning tall.
Triphyllocephaly is a cloverleaf skull deformity, derived from the Greek word triphyllos, meaning trefoil, with 3 leaves. This is a specific type of multiple-suture synostosis characterized by a head shaped like a cloverleaf, which manifests as a trilobular head with pronounced frontal bossing, temporal bulging, and a flat posterior skull.
German terms appear in the literature. Turmschädel means turricephaly, and kleeblattschädel 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 (SSCs), 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 fusion of the coronal and lambdoid sutures. 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 can include a mixture of otherwise unclassifiable combinations of affected sutures.
Craniosynostosis is also seen in the context of various syndromes, over 70 types. The most common syndromes encountered in clinical practice are Crouzon syndrome and Apert syndrome, followed by Saethre-Chotzen syndrome, and Pfeiffer syndrome. These syndromes are all characterized by bilateral coronal synostosis of varying severity, often combined with some degree of sagittal synostosis. The typically observed brachycephaly results in 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 syndromic cases.
A flat forehead and characteristically low-set ears are common. Patients, particularly those with Apert syndrome, tend to develop turricephaly, a feature not commonly seen in persons with other syndromic forms. Other extracranial abnormalities are commonly observed as part of the syndromes. In persons with Crouzon or Apert syndrome, 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.
The overall prevalence of craniosynostosis is estimated as 1 case in 2000 live births. Crouzon syndrome has an prevalence of 1 case in 25,000 live births. Apert syndrome has an prevalence of 1 case in 60,000 live births. Saethre-Chotzen and Pfeiffer syndromes are much less common.
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 and the syndromes were diagnosed purely on clinical examination findings. Renewed interest and considerable advances in the techniques used in studying genetics have contributed significantly 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. Crouzon syndrome is autosomal dominant in approximately 75% of cases, whereas Apert syndrome is sporadic in 95% of cases. Familial cases are frequent, constituting 25-46% of the total number of cases, with variation over 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. In familial cases, variable vertical and horizontal penetrance has been observed. In a recent publication, an argument for unilateral coronal craniosynostosis in Abraham Lincoln’s family is described.
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 syndromes. Most of the syndromic craniosynostosis cases involve the fibroblast growth factor receptor (FGFR) gene FGFR2.[23, 24, 25, 26, 27] The presence of mutations in the group of genes coding for 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 (FGFs). 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 are very similarstructurally.
Crouzon syndrome has been attributed to FGFR2 on 10q25-26. In the case of Crouzon syndrome with acanthosis nigrans, FGFR3 at Ala931Glu has been linked to the syndrome. Currently, 25 mutations have been identified on the FGFR2 gene and implicated in the pathogenesis of Crouzon syndrome.
Almost all cases of Apert syndrome are due to 1 of the 2 described mutations of the FGFR2 gene, located on 10q26. Specifically, Ser252Trp accounts for 66% of Apert syndrome cases and associated with cleft palate and increased visual impairment. The Pro253Arg mutation is responsible for 33% of Apert syndrome cases and is associated with optic disc pallor.
Mutations of both FGFR1 and FGFR2 genes have been described in Pfeiffer syndrome, each corresponding to phenotypes of different clinical severity.[30, 31, 32] Pfeiffer syndrome has been specifically mapped to 8p and 10q.
Muenke syndrome represents a syndrome that was diagnosed on a genetic basis and not purely on clinical examination findings. Families diagnosed as having a variant of Pfeiffer syndrome were evaluated genetically and found to have a common mutation in the FGFR3 gene linked to chromosome 4, based on work performed in the Muenke laboratory. Information on the individuals affected by the mutation and the genetic basis for the syndrome was published in 1997.
Saethre-Chotzen syndrome is due to mutations in the TWIST gene, and these patients have profound developmental delay.
In 2010, a retrospective genetic study of craniosynostosis showed mutations as the cause in 37.5% of bilateral coronal, 17.5% of unilateral coronal, and 11% of multiple-suture synostosis. The mutations were absent in all patients with nonsyndromic metopic, sagittal, and lambdoid craniosynostosis.
Using immunocytochemistry techniques, abnormal osteoblastic activity has been observed in cultures of synostotic bone. Observations include decreased growth rate; decreased alkaline phosphatase production; and increased levels of osteocalcin, platelet-derived growth factor, and epidermal growth factor.
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. The ridges are palpable upon clinical examination and are observed at operation, both externally and on examination of the inner table of the skull.
The overwhelming majority of abnormal head shapes seen in the clinic are of benign origin. Most commonly, positional plagiocephaly can masquerade as craniosynostosis to those with limited experience in diagnosing the condition. Positional plagiocephaly causes the skull to deform into a parallelogram shape with a proportional shift in the ears when viewed from above. The condition can often be corrected by having the caregiver nurse the affected infant on the side opposite the posterior flattening. The caregiver usually states the patient sleeps on a specific side, and the hair may be thinner over the flattened area. The parents or caregiver should be reassured.
Plagiocephaly resulting from a fused suture is a different entity. In addition to 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 and may require a continuous positive airway pressure (CPAP) device. Children with Crouzon syndrome often have visual problems and require early recognition to treat amblyopia and strabismus, particularly before age 2 years. Apert syndrome patients are more severely affected, often with cardiac, genitourinary, and gastrointestinal abnormalities.
Single-suture craniosynostosis (SSC) has classically been regarded as a benign entity in terms of neurologic function. However, in the 1990s, SSC was studied and was found to contribute to increased intracranial pressure (ICP) due to growth of the brain within an inadequate space. Studies have disagreed in the literature on whether SSC patients have delayed neurodevelopment when compared with the normative population and whether increased ICP is a contributing factor. It is recognized that craniosynostosis often begins during gestation, when the brain is most vulnerable. A redirection of both cortical and subcortical structures has been noted on MRI, revealing altered patterns of organization both preoperatively and postoperatively.
Da Costa et al evaluated neurodevelopmental implications in SSC patients who were untreated. Children with SSC displayed lower mean mental and motor scores than normal population averages. A clinically relevant motor delay was noted amongst the infants and none of the patients demonstrated accelerated development. Untreated SSC is associated with an increased incidence of developmental delay during early infancy, with motor skills being the most vulnerable during early development.
While it has been recognized that nonsyndromic SSC patients may succumb to mental and motor delayed development, Korpilahti et al recently showed that patients with SSC and deformational plagiocephaly are also at risk for deficient language acquisition. They found that 49% of SSC patients had normal linguistic development, but 30% had a slight delay and 21% had a severe delay in language. Moreover, there is a 3-times increased prevalence in severe language disorders compared with the general population. , children with deformable posterior plagiocephaly had defective language development, regardless of whether they underwent operative treatment. Approximately half of all SSC patients develop speech, cognitive, or behavioral issues.
Children with elevated ICP may experience chronic headaches, declining school performance, and gradual visual failure. Increased ICP is a risk factor for impaired language development before surgery. As children grow, abnormal facial appearance may have 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 (deformational) 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 or in the uterus. The head takes on a parallelogram shape when viewed from above. The posterior aspect of the head where the child tends to sleep, not surprisingly, often has a decreased amount of hair. Parents are counseled in conservative treatment by nursing the infant on the side that is more pronounced.
Lambdoid synostosis and deformational plagiocephaly can usually be distinguished clinically by viewing children from both a superior and posterior vantage. If infants with lambdoid synostosis are viewed from a posterior vantage, the ear on the flattened side appears inferiorly displaced and there is often a larger, palpable mastoid region. The skull takes the appearance of a trapezoid. If an infant with deformational plagiocephaly is viewed from a superior vantage, the ear (and sometimes the forehead) on the flattened side are anteriorly displaced.
Refer to the illustrations to appreciate the shapes of the various conditions when viewed from above.
No medical treatment exists for craniosynostosis. Indications for surgical treatment in the form of cranial vault reconstruction in the first few months of life include progressive facial and cranial deformity, intracranial hypertension, and progressive exophthalmos with risk to vision. The age at which surgery is performed is somewhat technique dependent, with the minimally invasive techniques benefiting from a younger child with a more malleable skull. In general, children younger than 9-12 months are the best candidates for corrective surgery.
Children aged 5-10 years may develop recurrent craniosynostosis 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.
During the clinical examination, observing the position of the forehead, 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 and in syndromic forms.
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. 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 synostosis, 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) scans. These clearly demonstrate the abnormally fused suture(s) and allow accurate preoperative planning. The surgeon can readily appreciate the morphology of the sites of interest and can formulate a plan, for instance, to determine how far the supraorbital bar must be advanced to correct the orbits. No less important in preoperative planning is the physical examination of the patient.
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, appropriate preoperative, intraoperative, and postoperative management is required 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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