Bicoronal Syndromic Craniosynostosis

Introduction

Syndromic craniosynostosis accounts for 8% to 24% of all patients with craniosynostosis. ^, The cause for syndromic synostosis is frequently genetic and often due to one of six frequently mutated genes: FGFR2, FGFR3, TWIST1, EFNB1, TCF12, and ERF. There are five major clinical syndromes associated with craniosynostosis and these frequently mutated genes; Apert, Crouzon, Muenke, Pfeiffer, and Saethre-Chotzen syndrome, although as we learn more about the genetics of synostosis, more named syndromes are being identified. In addition to the craniosynostosis, these five syndromes often share other common features such as exophthalmos, midface hypoplasia, and abnormal facies and cranial base and/or limb anomalies. Crouzon syndrome is the most common type of syndromic craniosynostosis, affecting approximately 1 in every 25,000 live births and can involve coronal, sagittal, and lambdoid sutures. ^, Arising most commonly from a mutation in the fibroblast growth factor receptor 2 (FGFR-2), individuals affected by Crouzon can have midface hypoplasia and significant turribrachicephaly. ^{, ,} Unlike Apert syndrome, this syndrome does not present with hand or foot anomalies. ^, Apert syndrome is present in approximately 1:100,000 live births, and is commonly associated with mutations in the FGFR-2 gene. ^{, ,} The most common presentation is bicoronal craniosynostosis (BCS) with turribrachycephaly, midface hypoplasia, and syndactyly. ^{, ,} Similar to Crouzon and Apert syndromes, Pfeiffer syndrome is one of the rarer syndromic forms of craniosynostosis, with an estimated incidence of 1 in every 100,000 live births, and can affect multiple sutures, with coronal being the most common. ^{, , , ,} The majority of Pfeiffer cases are also associated with FGFR-2, but about 5% express FGFR-1 instead, demonstrating a less severe phenotype. In general, and dependent on severity, a typical phenotype for this syndrome involves a high forehead, and wide-set proptosis as well as broad thumbs and toes.

Stemming from a different set of mutations, Saethre-Chotzen syndrome is caused by mutations in the TWIST-1 gene in chromosome 7p21.2. ^{, ,} The incidence averages 1 in 25,000 to 50,000 births, and in addition to the synostosis, this condition may include asymmetrical face, a low-lying hairline, droopy eyelids, and occasionally hand and foot anomalies, although not as severe as seen in Apert syndrome. ^, Relating to craniosynostosis, Saethre-Chotzen syndrome specifically affects the coronal suture, either unilaterally or bilaterally. The fifth syndrome, Muenke syndrome, derives its name from the first report of its associated genetic mutation (FGFR-3 pro250Arg chromosome 4p). ^, With an incidence of 1 in 10,000, this syndrome affects the coronal sutures and is characterized by an abnormally shaped head and wide-set eyes like in Pfeiffer syndrome, flatter cheek bones, and sometimes even hearing loss. ^{, ,} Over time, infants born with craniofacial syndromic malformations have presented several treatment challenges. The fundamental goals of surgery are to allow normal brain growth, prevent elevated intracranial pressure (ICP) and mitigate against development delay, and to assure the best morphology of the skull. As many of the syndromic conditions present with turribrachycephaly, a condition which is difficult to treat in a single stage open operation, there has been an evolution over time on how best to treat syndromic cases. Many centers now advocate for an early surgery to help mitigate the turricephaly.

Until recently, two main surgical techniques have been performed to correct bilateral and unilateral coronal syndromic craniosynostosis, which typically involve a fronto-orbital advancement (FOA). This is best done when the bones have substantially formed and gained adequate thickness, often closer to 10 to 12 months of age. Unfortunately, by that time the turricephaly is well established, and therefore quite difficult to treat. As a result, many centers have added an early posterior fossa release, often utilizing distractor techniques, which involves a three surgery treatment paradigm to correct the skull deformity. In this chapter we review the role of early endoscopic suturectomy with helmet therapy as a treatment option for syndromic synostosis, which can prevent the formation of turricephaly and offers the hope of a single operation to treat the condition.

Common Presentations of Syndromic Synostosis

BCS, either in isolation or associated with other sutural fusions, is the most common form of syndromic craniosynostosis. ^{, ,} It is characterized by an increased biparietal diameter and significant frontal flattening with retrusion of the supraorbital ridge. This head shape is known as brachycephaly. As a result of the frontal retrusion, there is often compensatory superior growth of the cranium. In those cases where the parietal height is also affected, the most appropriate term to name this pathology is turribrachycephaly. Coronal synostosis can also occur on just one side, and is known as unicoronal synostosis (UCS). This can cause quite an asymmetry in head shape, and typically presents as a flatter forehead and brow on the affected side, as well as nasal root deviation toward the affected side, which can continue down toward the chin point and always causes ear asymmetry with advancement of the ear on the affected side. ^,

Although the coronal sutures are the ones most commonly affected in syndromic synostosis, any of the sutures may be involved, and this can be present either at presentation or evolve over time. Lambdoid synostosis, generally the rarest form of craniosynostosis, can be seen more commonly in syndromes. Sagittal synostosis (SS), the most common suture fused in the single suture synostosis group, is not the most common suture fused in syndromic cases. That said, it can occur and cause the skull to form a narrow shape as the bones elongate in the frontal and occipital regions only. Finally, metopic synostosis can occur and when the fusion does lead to a significant trigonocephaly, surgery may be warranted. For this chapter, we will focus primarily on the endoscopic treatment of bilateral coronal synostosis associated with syndromic synostosis.

Literature Review

In the 1990s Jimenez and Barone introduced the endoscopic strip craniotomy (ESC) using minimal incisions, followed by postoperative orthotic therapy. Multiple studies have now demonstrated this technique to be an effective and safe treatment for craniosynostosis. ^, Indeed, this seems to be well established for many forms of single suture synostosis. ESC is undertaken at a much younger age than the cranial vault reconstruction operations and, thus, the early sutural release may prevent the progression of craniofacial asymmetry. Indeed, studies have revealed this to be true for several types of synostosis. Early ESC and helmet therapy in USC results in comparable brow symmetry and better overall facial symmetry than FOA done in late infancy. It is possible that FOA done at a similar age (younger than 4 months) might yield comparative results, but it is not practical due to the higher operative risk and because cranial bones are fragile and difficult to stabilize in children of this age. ^, Another advantage of ESC is that, by and large, it leaves the remainder of the cranium and the normal sutures untouched and thus maintains normal growth potential over the life of the patient. In UCS, although a single side is affected, the FOA surgery requires a bilateral reconstruction. Advancement of the forehead and bandeau creates bony gaps that rapidly ossify; as such, functional “sutures” never arise. The absence of functional sutures and the inability to predict growth patterns over time may be why a higher rate of recurrent fronto-orbital asymmetry is reported after FOA. Indeed, after the minimally invasive operations, multiple authors have reported “neosuture” formation, essentially a normal suture forming where one had been absent. ^,

ESC seems to have had unanticipated positive consequences. As noted earlier, it can improve facial asymmetry in UCS. It has also been reported that patients managed with ESC have significantly less risk of astigmatism and ocular torticollis than those managed by FOA, as this larger technique improves only the anterior aspect of the orbit having little impact on posterior orbital cavity without any correction of ocular imbalance. ^, It is likely that early release of the coronal suture results in better normalization of orbital shape than occurs with a later FOA. In addition, with the smaller operation, as the orbit expands, the muscle, which has never been detached from the periorbita and bone, might also normalize. For SS, ESC is an effective treatment with comparable head growth and aesthetic outcomes and less perioperative morbidity than calvarial vault reconstruction (CVR).

Although fairly well established as an effective treatment for single suture synostosis, the benefits of ESC for syndromic and multisuture synostosis are just becoming elucidated. Recently, studies regarding BCS showed that endoscopic suturectomy and helmeting can improve turricephaly and correct frontal bossing and brachycephaly. The significant advantage of ESC is likely the age at surgery and the associated prophylactic effect it affords as once secondary conditions such as turricephaly develop, it is challenging to correct. ^, Therefore, early interventions that prevent worsening turricephaly promise good outcomes and experience is now making it clear that this indeed occurs. On craniometric analysis, morphologic improvement appears at least equivalent to the improvement seen with posterior distraction followed by FOA.

The typical paradigm employed by many centers at this point for the treatment of turribrachycephaly secondary to syndromic bilateral coronal synostosis, involves a three-stage surgical repair. First the occipital bones are released, followed by placement of the distractors; second the removal of the distractors 6 to 8 weeks later; and finally, an FOA closer to 10 to 12 months of age. It is possible that it can be two stages, as one comparative study has shown that distraction did not appear to provide any advantages with respect to either accomplished skull enlargement or the ability to eliminate the need for later subsequent procedures. A potential advantage of endoscopic treatment is that it can achieve the desired result in a single operation. That said, any surgeons treating these conditions must understand that suture fusion/refusion is a dynamic process in syndromic patients and never assume the outcome at the onset of treatment. Syndromic patients, like all patients with synostosis, need to be followed closely over time by a multidisciplinary craniofacial clinic. It is likely, and seems to be supported by evolving literature, that there will be a higher rate of reoperation in patient with syndromic craniosynostosis.