Syndromic craniosynostosis: current concepts in intracranial hypertension, cranial base pathology, and surgical management

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Arch Craniofac Surg. 2026;27(3):113-119

Publication date (electronic) : 2026 June 20

doi : https://doi.org/10.7181/acfs.2026.0080

So Young Lim

Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

Correspondence: So Young Lim Department of Plastic Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, 81 Irwon-ro, Gangnam-gu, Seoul 06351, Korea E-mail: pslisy@naver.com

Received 2026 May 24; Revised 2026 May 24; Accepted 2026 June 8.

Abstract

INTRODUCTION

Craniosynostosis refers to premature fusion of one or more cranial sutures and occurs approximately 1 in 2,000 live births. Syndromic craniosynostosis comprises approximately 15% of all craniosynostosis cases and is commonly associated with fibroblast growth factor receptor (FGFR) mutations [1,2]. Compared with nonsyndromic craniosynostosis, syndromic disease demonstrates more severe craniofacial deformities, multisuture involvement, and higher incidences of neurological complications including elevated intracranial pressure (ICP), hydrocephalus, visual impairment, and developmental delay [3-7].

Representative syndromic craniosynostoses include Crouzon syndrome, Apert syndrome, Pfeiffer syndrome, and Saethre- Chotzen syndrome. Among these disorders, Crouzon syndrome is one of the most frequently encountered forms and is characterized by bicoronal or multisuture synostosis, exorbitism, midface retrusion, maxillary hypoplasia, hypertelorism, and progressive craniofacial dysostosis.

Historically, the pathophysiology of craniosynostosis was interpreted primarily according to the concept that premature suture fusion restricts cranial expansion and reduces intracranial volume (ICV), thereby causing increased ICP [2,8-10]. However, recent radiologic studies have demonstrated that many patients with syndromic craniosynostosis maintain near-normal ICVs through compensatory cranial growth despite severe craniofacial deformity.

Consequently, intracranial hypertension is now recognized as a multifactorial process involving cerebrospinal fluid (CSF) circulation abnormalities, venous hypertension, airway compromise, hydrocephalus, and cranial base pathology [4,6,7,11]. Recent interest has focused on the role of cranial base sutures and synchondroses in syndromic craniosynostosis [1,12-14]. Although major calvarial sutures have traditionally received greater clinical attention, increasing evidence suggests that premature cranial base fusion contributes significantly to recurrent ICP, facial dysmorphology, and progressive disease severity [1,13,14].

The purpose of this review is to summarize current concepts regarding syndromic craniosynostosis with emphasis on intracranial hypertension, cranial base fusion, secondary craniosynostosis, hydrocephalus, neurocognitive dysfunction, and contemporary surgical management.

EMBRYOLOGY AND BIOLOGY OFCRANIAL SUTURES

Cranial sutures are fibrous articulations that permit skull expansion during rapid brain growth in infancy and childhood. Physiologic maintenance of suture patency requires tightly regulated interactions among osteoblasts, mesenchymal stem cells, growth factors, and extracellular signaling pathways [2]. The six major calvarial sutures consist of the metopic, sagittal, paired coronal, and paired lambdoid sutures. Under normal physiologic conditions, the metopic suture closes during infancy at approximately 7–9 months of age, whereas the sagittal, coronal, and lambdoid sutures generally remain patent until adulthood [1,2]. Disturbance of the balance between suture patency and ossification may result in craniosynostosis. In syndromic disease, FGFR mutations accelerate osteogenic differentiation and promote premature ossification of both major calvarial sutures and cranial base structures [1,2,12,14].

CRANIAL BASE SUTURES AND SYNCHONDROSES

Compared with the major calvarial sutures, cranial base sutures and synchondroses undergo physiologic fusion earlier, often by the end of adolescence. Eight paired cranial base sutures include the frontoethmoidal, frontosphenoidal, sphenoparietal, sphenosquamosal, sphenopetrosal, parietosquamosal, parietomastoid, and occipitomastoid sutures. Major cranial base synchondroses include the sphenoethmoidal, spheno-occipital, petro-occipital, anterior intraoccipital, and posterior intraoccipital synchondroses (Fig. 1).

Fig. 1.

Names and abbreviations of eight cranial base sutures and five cranial base synchondroses. Sutures: FrEt, frontoethmoidal; FrSp, frontosphenoidal; SpPa, sphenoparietal; SpSq, sphenosquamosal; SpPe, sphenopetrosal; PaSq, parietosquamosal; PaMa, parietomastoid; OcMa, occipitomastoid. Synchondroses: SpEt, sphenoethmoidal; SpOc, spheno-occipital; PeOc, petro-occipital; AIO, anterior intraoccipital; PIO, posterior intraoccipital.

Vu et al. demonstrated that cranial base sutures and synchondroses follow distinct physiologic closure timelines throughout childhood and adolescence [13,15,16]. Using computed tomography (CT)-based grading analysis, the authors reported that anterior cranial base sutures tend to close earlier than posterior sutures, while synchondroses demonstrate variable closure patterns independent of simple anterior-posterior distribution. These findings provide important baseline physiologic data for understanding premature cranial base fusion in syndromic craniosynostosis and support the concept that abnormal cranial base ossification may contribute to recurrent intracranial hypertension and progressive craniofacial dysmorphology.

Physiologic closure patterns of these structures have been investigated using CT-based grading systems. Posteriorly located cranial base sutures generally close later than anterior sutures, although synchondroses do not always follow the same pattern. Premature cranial base fusion may significantly alter craniofacial morphology and intracranial dynamics [1,13]. Syndromic patients, especially those with FGFR2 mutations, appear to demonstrate accelerated fusion of cranial base sutures compared with nonsyndromic patients and healthy controls.

This accelerated fusion may contribute to maxillary hypoplasia, facial asymmetry, skull base deformity, and recurrent increased ICP. In addition to the major sutures, the cranial base contains multiple minor sutures and synchondroses that contribute to craniofacial growth. These structures are increasingly recognized as important contributors to syndromic craniosynostosis pathophysiology [14,17].

ICV AND ICP

Contemporary understanding

Advanced imaging studies have demonstrated that many syndromic patients maintain relatively normal ICV despite severe cranial deformity. Elevated ICP therefore cannot be explained solely by reduced ICV because many patients maintain relatively normal ICV through compensatory cranial growth [4,6,7,9- 11]. Some patients with severe multisuture fusion demonstrate minimal signs of intracranial hypertension, whereas others with limited suture involvement develop substantial neurological complications [18-21]. The incidence of increased ICP is generally associated with the number of fused sutures. Multisuture craniosynostosis demonstrates increased ICP in more than 50% of patients, whereas single-suture craniosynostosis demonstrates lower rates [8,9]. Nevertheless, the relationship is not absolute, suggesting the existence of additional pathophysiologic mechanisms.

The patient shown in Fig. 2A and B demonstrated severe intracranial hypertension despite patency of all major cranial sutures, accompanied by marked cranial deformity and severe craniofacial dysmorphology. Conversely, the patient shown in Fig. 2C and D exhibited relatively mild craniofacial deformity and no definite evidence of elevated ICP despite the presence of pan-craniosynostosis. These contrasting cases suggest that increased ICP and craniofacial severity in syndromic craniosynostosis cannot be explained solely by the number or extent of fused calvarial sutures, and that additional factors such as cranial base pathology, CSF dynamics, venous hypertension, and airway compromise may substantially influence disease progression [20-22].

Fig. 2.

(A, B) A patient demonstrating severe intracranial hypertension despite patency of all major cranial sutures, accompanied by marked cranial deformity and severe craniofacial dysmorphology. Conversely, the patient shown in (C, D) exhibited relatively mild craniofacial deformity and no definite evidence of elevated intracranial pressure despite the presence of pan-craniosynostosis.

MECHANISMS OF INCREASED ICP

CLINICAL MANIFESTATIONS OF INCREASED ICP

Recent studies demonstrated that syndromic craniosynostosis patients may follow heterogeneous clinical courses despite similar initial cranial deformities. Kim et al. [23] reported three distinct postoperative patterns: patients with stable postoperative courses, patients with recurrent intracranial hypertension requiring revision surgery, and patients with relatively mild craniofacial deformity without definite signs of increased ICP who required only midface corrective procedures. The study further demonstrated that recurrence of increased ICP may occur several years after apparently successful cranial vault remodeling. Recurrent intracranial hypertension was associated with papilledema, ventriculomegaly, subjective symptoms, and especially diffuse beaten-copper appearance on skull radiographs [23]. Elevated ICP may produce irreversible neurological and ophthalmologic complications including optic atrophy, blindness, developmental delay, and neurocognitive impairment.

Clinical symptoms are frequently nonspecific and include headache, vomiting, irritability, altered mentality, and bulging fontanelle [24]. Because these symptoms correlate poorly with measured ICP, reliable surveillance remains challenging. Papilledema remains one of the most clinically useful indicators of increased ICP [3]. Increased ICP causes optic nerve swelling, optic disc elevation, and blurring of optic disc margins. However, papilledema may occur relatively late during disease progression [3]. Visual evoked potentials may facilitate earlier detection of intracranial hypertension before irreversible optic nerve damage occurs [3,11]. Radiologic findings such as the copper-beaten skull appearance may also correlate with recurrent elevated ICP during postoperative follow-up [3,9]. Kim et al. [23] reported that among indirect surveillance methods, diffuse beaten-copper appearance on skull radiographs appeared to be one of the most reliable noninvasive indicators of recurrent increased ICP during long-term follow-up (Fig. 3).

Fig. 3.

Case presentation. (A) Preoperative CT scan demonstrating a diffuse beaten-copper appearance. (B) Five-year postoperative follow-up CT showing favorable progress and (C) recurrent beaten-copper appearance 6 years postoperatively. (D) Disappearance of the beaten-copper appearance 6 years after additional endoscopic third ventriculostomy. CT, computed tomography.

NEUROCOGNITIVE DYSFUNCTION

Neurocognitive dysfunction represents a major long-term concern in syndromic craniosynostosis. Elevated ICP, chronic papilledema, venous hypertension, hydrocephalus, impaired cerebral perfusion, and sleep-disordered breathing may contribute to abnormal neurodevelopment [4,5]. Several studies have suggested associations between craniosynostosis and ADHD (attention- deficit/hyperactivity disorder), learning difficulties, language delay, and executive dysfunction [5]. Importantly, neurodevelopmental outcomes remain highly variable, emphasizing the importance of multidisciplinary developmental monitoring [5].

SECONDARY CRANIOSYNOSTOSIS

Secondary craniosynostosis was identified in approximately one-half of patients with recurrent intracranial hypertension in the postoperative period, emphasizing the progressive nature of syndromic disease and the necessity for long-term multidisciplinary monitoring. Secondary craniosynostosis refers to postoperative fusion of previously patent sutures following cranial vault surgery [11,23]. Secondary craniosynostosis may be categorized as: (1) iatrogenic secondary craniosynostosis and (2) idiopathic secondary craniosynostosis. Iatrogenic secondary synostosis develops in surgically manipulated sutures, whereas idiopathic secondary synostosis develops in previously untreated sutures [25,26]. Postoperative refusion may contribute to recurrent intracranial hypertension and progressive craniofacial deformity, emphasizing the need for long-term postoperative monitoring [11]. Secondary sagittal synostosis appears particularly common (Fig. 4).

Fig. 4.

Preoperative (A) and postoperative (B) 3D-CT image of a patient that revealed idiopathic secondary synostosis in the sagittal suture after surgical correction of bicoronal synostosis. 3D-CT, three-dimensional computed tomography.

SURGICAL MANAGEMENT

The primary goals of surgical treatment include prevention of elevated ICP, protection of visual function, optimization of neurodevelopment, correction of cranial deformity, improvement of airway function, and facilitation of psychosocial development. Because syndromic craniosynostosis demonstrates progressive disease behavior, repeated procedures are frequently required [7,11,27,28]. Fronto-orbital advancement remains one of the most widely utilized procedures in syndromic craniosynostosis. Fronto-orbital advancement enlarges the anterior cranial vault, improves orbital protection, and corrects frontal deformity [27,28]. Total cranial vault remodeling provides extensive cranial reshaping and intracranial expansion. In syndromic patients with severe elevated ICP, cranial vault remodeling may be necessary during infancy or early childhood. However, recurrent intracranial hypertension may occur despite apparently adequate cranial expansion.

Endoscopic strip craniectomy combined with postoperative helmet therapy has gained increasing popularity in selected infants diagnosed early [29,30]. Advantages include reduced blood loss, shorter operative time, smaller incisions, and faster recovery [29,30]. Nevertheless, concerns remain regarding incomplete correction, postoperative asymmetry, and early refusion [10]. Distraction osteogenesis allows gradual cranial expansion with less extensive bone manipulation and may be particularly useful in syndromic patients with recurrent intracranial hypertension [7,11,28]. Posterior distraction osteogenesis may be especially effective in syndromic patients without severe orbital compromise. Progressive expansion may improve ICV while reducing operative morbidity. Revision surgery, including repeat cranial vault remodeling, CSF diversion procedures, and midface advancement, may be necessary in selected patients [4,7,11,28,31].

CRANIAL BASE FUSION AS A PROGNOSTIC FACTOR

Recent studies have increasingly emphasized the prognostic significance of cranial base fusion in syndromic craniosynostosis [1,12-14]. Patients with recurrent elevated ICP requiring repeated cranial vault remodeling procedures appear to demonstrate more severe cranial base fusion than patients with stable postoperative courses. Particularly important structures include: (1) frontosphenoidal suture, (2) sphenoparietal suture, (3) sphenosquamosal suture, (4) parietomastoid suture, (5) occipitomastoid suture, and (6) petro-occipital synchondrosis. Persistent cranial base restriction may continue to limit intracranial accommodation even after calvarial expansion surgery. Consequently, careful radiologic evaluation of cranial base sutures during initial assessment may facilitate prediction of disease severity and future surgical requirements [14,32].

FUTURE PERSPECTIVES

Future investigations should focus on longitudinal cranial base fusion analysis, elucidation of the molecular mechanisms underlying premature cranial base ossification, artificial intelligence- assisted CT evaluation, identification of predictive biomarkers for recurrent ICP, optimization of surgical timing, and assessment of long-term neurodevelopmental outcomes. Improved understanding of cranial base pathology may permit more individualized treatment strategies and improved longterm neurological outcomes.

CONCLUSION

Syndromic craniosynostosis represents a progressive and multifactorial disorder characterized by multisuture fusion, recurrent intracranial hypertension, hydrocephalus, cranial base pathology, and neurocognitive dysfunction. Current evidence indicates that elevated ICP cannot be explained solely by reduced ICV. Instead, abnormal CSF circulation, venous hypertension, upper airway obstruction, secondary synostosis, and premature cranial base fusion appear to contribute significantly to disease progression. Recent investigations demonstrated significant associations between premature cranial base fusion and recurrent elevated ICP in Crouzon syndrome. These findings suggest that cranial base pathology may represent both an important prognostic factor and a potential therapeutic target in syndromic craniosynostosis. Comprehensive multidisciplinary management with long-term radiologic, ophthalmologic, neurologic, and developmental surveillance remains essential for optimizing patient outcomes.

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