Crouzon syndrome is a rare genetic disorder characterized by the premature fusion of certain sutures of the cranial vault, base, orbital, and maxillary region, leading to craniofacial dysmorphology. The severity of craniosynostosis varies among individuals. The clinical presentation of this congenital deformity depends on the pattern and timing of sutural fusion. Crouzon syndrome is caused by a mutation in genes that control bone development, particularly the fibroblast growth factor receptor 2 (FGFR2) gene. This report highlights the varied clinical presentation of a 13-year-old patient with Crouzon Syndrome, featuring the craniofacial manifestations, associated dental characteristics, and the benefit of a multidisciplinary rehabilitation approach focusing on management of the condition in the dental context.

Severe proptosis in a newborn with genetically confirmed Crouzon syndrome

636 - Multidisciplinary Approach to Crouzon Syndrome with Osteogenic Distraction – A Case Report

Introduction: Crouzon syndrome is a rare autosomal dominant genetic disorder associated with a mutation in the fibroblast growth factor receptor 2 (FGFR2) gene, which affects the first branchial arch. It is characterised by premature craniofacial dysostosis, resulting in skull deformities, facial anomalies, and proptosis. Patient Presentation: We report a case of Crouzon syndrome who presented with no neurological symptoms and was incidentally found to have arteriovenous malformations in the vertex and occipital region. Management and outcome: This case elucidates the importance of considering vascular anomalies in patients with syndromic craniosynostosis, and imaging strongly contributes to early identification of AVMS and can guide multidisciplinary evaluation and intervention to optimise outcomes in such complex presentations. Conclusion and contribution: The association between Crouzon syndrome and AVMs remains poorly understood; therefore, further studies and reporting of similar cases may help establish a better pathophysiological link. Keywords: Crouzon, Craniosynostosis, Arteriovenous malformations

Frontofacial monobloc advancement (FFMBA) is among the most complex craniofacial surgeries performed; however, the learning curve for this procedure has not been previously documented. In this study, we retrospectively investigated the learning process of a newly trained surgeon performing FFMBA. Twenty patients who underwent FFMBA between 2015 and 2024 were included in this study. All surgeries were performed by the same craniofacial surgeon and pediatric neurosurgeons. Operative time, blood loss, and complications were retrospectively analyzed using the Wilcoxon matched-pairs signed-rank test, with statistical significance set at P<0.01. The study included 14 patients with Crouzon syndrome, 5 with Pfeiffer syndrome, and 1 with Beare-Stevenson syndrome (mean age: 10.6±12.7y; range: 3-62y). Operative time ranged from 218 to 510 minutes (mean: 321.9±83.5min), and blood loss ranged from 350 to 2822mL (mean: 944.1±621.3mL), gradually decreasing over time. The patients were categorized into two groups based on their history of frontal surgery. Operative time and blood loss were significantly higher in patients with previous surgeries (P<0.01). Complications, including meningitis, distractor prolapse, frontal bone resorption, and recurrent nerve palsy, occurred only in the previously treated group. The learning curve for FFMBA is influenced by the patient's surgical history, particularly previous frontal surgeries. Careful case selection and collaboration within a multidisciplinary craniofacial team are essential for safely and effectively implementing this complex procedure.

Background:Le Fort (LF) III midface distraction osteogenesis is one of the main techniques for correcting midface deficiency encountered in craniofaciosynostosis. However, regardless of the technique used, there may be a deterioration in the result, with a recurrence of facial hypoplasia, requiring a new procedure to advance the midface.Methods:In this retrospective study, computed tomography scans before and after LF III distraction osteogenesis of 7 patients (3 boys and 2 girls with Crouzon syndrome, 1 boy with Apert syndrome, and 1 boy with Pfeiffer syndrome) were analyzed in vestibular orientation. The ages ranged from 4 to 11 years old. All patients presented with syndromic craniofaciosynostosis with class III malocclusion and proptosis. The 3 cranial fossae were segmented slice by slice, and their volumes were calculated. The total intracranial volume was calculated by summing the volumes of the 3 cranial fossae. The Wilcoxon signed-rank test was used to compare the measured values before and after LF III distraction. A P value of less than 0.05 was considered statistically significant.Results:Total intracranial volume significantly increased (6%; P = 0.016) in the total study group. Volumes of the anterior and middle cranial fossae increased insignificantly (22.6%, P = 0.33; 4.8%, P = 0.29). The volume of the posterior cranial fossae insignificantly decreased (0.3%, P = 0.58).Conclusions:A significant increase in total intracranial volume after LF III advancement in syndromic craniofaciosynostosis patients was reported.

Abstract Introduction Muenke syndrome is a form of syndromic craniosynostosis caused by a specific mutation in the FGFR3 gene. It is characterized by premature fusion of the coronal sutures, resulting in craniofacial abnormalities, hearing impairment, and developmental delays. It remains underdiagnosed, particularly in low-resource settings. Objective To report a rare case of Muenke syndrome in The Gambia that was initially misdiagnosed as Graves’ disease. Methods A 12-year-old girl presented with bilateral proptosis, abnormal skull shape, hearing difficulties, and developmental concerns. Clinical evaluation included detailed physical examination, thyroid function testing, audiology assessment, and imaging. Genetic testing was unavailable. Results Thyroid function was normal. The patient exhibited macrocephaly with scaphocephaly, a flat nasal bridge, bilateral syndactyly of the toes, and bilateral ear pits. She had significant speech delay and learning difficulties. Audiological review confirmed bilateral sensorineural hearing loss. A CT scan of the skull revealed bi-coronal synostosis with a copper beaten appearance. Foot X-rays showed metatarsal coalition. Differential diagnoses considered included Crouzon and Apert syndromes, but findings were most consistent with Muenke syndrome. Conclusion This case underscores the importance of comprehensive clinical and radiologic evaluation in pediatric patients with atypical proptosis. In resource-limited settings, Muenke syndrome may be mistaken for more common conditions like Graves’ disease. Early recognition enables multidisciplinary care, including surgical correction, speech and hearing support, and genetic counseling, which are crucial for improving patient outcomes.

Introduction: Chiari malformation I (CM1) often results from craniocerebral disproportion such as that caused by craniosynostosis (CS). The association between CM1 and CS has been described in several retrospective studies, but a comprehensive meta-analysis of the cumulative data has not been reported. This systematic review and meta-analysis aims to quantify the association between CM1 and CS, including both non-syndromic and syndromic subtypes. Methods: A systematic review and meta-analysis was performed following PRISMA guidelines. Search terms related to Chiari malformation and craniosynostosis (including multi-sutural and single-suture variants) were applied to 3 databases—OVID (Medline), CINAHL, and Scopus—as well as 1 trial register, Cochrane Trials. Three independent reviewers screened records by review. Studies were included if they reported on the presence of CM1 in patients with any type of craniosynostosis. Results: The initial search yielded 688 articles with 21 meeting inclusion criteria. A total of 1617 patients were included in the study. CM1 was reported in 11% (n = 71) patients with non-syndromic single suture craniosynostosis, 22.7% of patients with syndromic craniosynostosis, and 28.0% of patients with non-syndromic multi-suture craniosynostosis. In patients with single-suture synostosis, the rates were highest in lambdoid synostosis (45.5%) and uni-coronal synostosis (7.14%). Among syndromic cases, the rates were highest in patients with Pfieffer syndrome (68.2%), Crouzon syndrome (44.9%), and Apert syndrome (18.1%). Conclusion: This meta-analysis demonstrates a strong association between Chiari malformation type I (CM1) and both lambdoid craniosynostosis and multi-suture craniosynostosis. Furthermore, CM1 is significantly associated with syndromic craniosynostosis, particularly in patients with Pfeiffer, Crouzon, and Apert syndrome. These results underscore the need for thorough assessment and vigilant screening for CM1 in higher-risk craniosynostosis subtypes, as this may optimize clinical decision-making, guide surgical strategies, and improve overall patient care.

This study presents a paleopathological analysis of individual T4.2 from the archaeological site of the castle of Zorita de los Canes (Guadalajara, Spain). The individual exhibits ultradolichocephaly and was dated between the 13th and 15th centuries. Based on the context, the individual could have been a member of the military–religious Order of Calatrava. Standard bioanthropological and paleopathological methods were applied. The results indicate a male aged between 45 and 49 years with a maximum cranial length and width of 230 mm and 122 mm, respectively. The cranial index (53%) allows him to be classified as ultradolichocephalic. The remains present craniosynostosis at the sagittal, squamosal and sphenofrontal sutures, together with underdevelopment of the skull base width and a dolichognathic mandible with the possible presence of type III prognathism. The left hemimandible and hemimaxilla display a large amount of tartar covering the occlusal, labial and lingual areas of the teeth completely. The right hemimandible and hemimaxilla exhibit almost no tartar, and some teeth were lost in vivo. In addition, two stab wounds—to the external occipital protuberance and to the left temple—as well as a contused injury in the left tibia, can be observed without evidence of bone remodeling. Differential diagnosis indicates a case consistent with Crouzon syndrome. This individual is of particular significance because he was a possibly knight of the Order of Calatrava who presents a syndromic craniosynostosis consistent with Crouzon syndrome and exhibits lesions, which may suggest that he could have died in battle.

Crouzon syndrome (CS) is a rare genetic condition characterised by craniofacial malformations due to mutations in the FGFR2 gene. This study aimed to evaluate the contributing factors for Angle's Class III malocclusion in patients with CS through cephalometric analysis. Six patients with confirmed CS diagnosis were included in the study. Cephalometric measurements were performed using CT scans and compared to established norms. Pathogenic variants in the FGFR2 gene were identified in all patients. Phenotypic and cephalometric characteristics were assessed in each patient. Results showed consistent craniofacial abnormalities, including midface retrusion, mandibular prognathism, and malocclusion. Cephalometric analysis revealed specific patterns indicating growth deficiency at the posterior base of the skull, maxillary retroposition, and an anterior accommodation of the mandibular condyles in the glenoid fossa. These findings provide valuable insights into the underlying factors contributing to Angle's Class III malocclusion in patients with Crouzon syndrome.

Intermediate butterfly osteotomy with rigid external distraction in Crouzon syndromes

Craniosynostosis is a multigenic congenital condition in which one or more calvarial sutures have prematurely fused during the development of the fetus. Pathogenic variants in FGFR2 are associated with the development of syndromic craniosynostosis, such as Crouzon, Apert and Pfeifer syndromes. Investigation of FGFR2-linked craniosynostosis is hindered by the lack of appropriate in vitro models. Patient-derived human induced pluripotent stem cell (hiPSC) in vitro disease models provide the opportunity to investigate the disease, identify molecular targets for pharmaceutical treatments, and enable the generation of autologous pluripotent stem cell catalogues. Here, we report three patient-derived hiPSC lines carrying the C342Y, S252W or E565G FGFR2 pathogenic variant. The patient hiPSC lines express characteristic pluripotency markers and display distinct phosphorylation profiles under unstimulated conditions. FGFR2C342Y showed autophosphorylation in the absence of bFGF ligand, although downstream docking proteins PLCγ and FRS2α were not phosphorylated. FGFR2S252W and FGFR2E565G hiPSCs showed increased phosphorylation of docking proteins PLCγ and FRS2α, whereas FGFR2 was not phosphorylated. These patient hiPSC lines provide molecular and cellular options to investigate FGFR2-linked craniosynostosis in the patient-specific genomic context and develop therapeutic modalities.

Crouzon syndrome, which is a hereditary craniosynostosis, can be the result of inheritance from either parent, as well as de novo mutations in the FGFR2 gene. With a confirmed molecular genetic diagnosis, preimplantation genetic testing for monogenic diseases (PGT-M) is available for high-risk families. However, there is currently little information in the literature about using this approach to prevent this condition. The aim of our study was to describe the clinical case of IVF/ICSI with PGT-M for Crouzon syndrome with a successful outcome and confirmatory diagnostics. PGT-M was planned and performed for a married couple (aged 24 and 25), in which the husband had Crouzon syndrome. The husband’s father had a milder form of Crouzon syndrome and the pathogenic variant of the FGFR2 gene was in a mosaic form. During preparation, a testing system was selected for the pathogenic variant NM_000141.5(FGFR2):c.1007A>G (p.Asp336Gly) of the FGFR2 gene, and gene-linked polymorphic microsatellite markers. The STR markers in the husband’s father excluded chimerism for the pathogenic variant and indicated mosaicism with the involvement of germ cells. Molecular genetic analysis was performed using а nested PCR, with detection by fragment analysis for STRs and restriction analysis of the pathogenic variant. During the IVF program, superovulation stimulation and embryological procedures were performed according to standard protocols. Fertilization was achieved using the ICSI method, and blastocyst biopsy was done on the sixth day of development. For PGT-M, a direct analysis of pathogenic variants and an indirect analysis of selected informative STRs were used. The thawed embryos were transferred based on the results of preimplantation testing. We selected twelve STRs flanking the FGFR2 gene, eight informative ones were used during PGT-M. In the IVF program, 15 mature oocytes were obtained, then four blastocysts were biopsied. One of the four embryos inherited a normal paternal chromosome, the other three had the pathogenic variant and the associated risk haplotype. A singleton pregnancy has occurred as a result of embryo transfer recommended after PGT-M. Following the child’s birth, molecular diagnostics were performed, confirming the PGT-M result. The presented clinical case provides an effective example of IVF with PGT-M to prevent the birth of affected children in families with hereditary craniosynostosis.

The objective of this study was to review and present the experience, with the functional results as well as complications of the individuals who underwent facial middle-third advancement with rigid external device. We report a major complication (cerebral abscess) secondary to pin migration. There are functional and esthetics objectives when performing surgical procedures in middle facial third hypoplasia. Many have compared external and internal distraction devices use and results with a lack of evidence on perioperative morbidity; this study was designed to revise complications associated with external distraction. This retrospective study was conducted over a 5-year period, including 24 patients. Patient's characteristics, perioperative factors, and postoperative complications were revised. Twenty-four patients undergoing midfacial/fronto-orbital surgery, between 2020 and 2024 were included (Crouzon, Apert, and Kabuki syndromes, cleft lip and palate sequelae, and craniosynostosis cases). The mean follow-up was 39.5 months (±15.98 mo). Monobloc advancement was the most frequently performed procedure (45.8%), followed by Lefort-III (37.5%), Lefort-II (12.5%), and fronto-orbital advancement (8.3%). The mean advancement achieved was 18.9 mm (±6.06 mm). Of the total, 58.33% had no complications, with 37.5% and 4.16% having grade II and grade III-B complications (Clavien-Dindo System). The patient from the case report, had a cerebral abscess, whose course required the removal of the external device, getting a 6.7 mm advancement. Distraction osteogenesis remains a great procedure where significant midfacial advancement is required, despite the complication rate. There should be a well-defined preoperative and postoperative protocol to avoid major complications from happening.

Crouzon syndrome represents an autosomal dominant genetic disorder primarily characterized by craniofacial malformations. Recent advancements have enabled the successful derivation of periosteal stem cells from the periosteum, a critical reservoir of osteogenic progenitor cells. This investigation employs periosteal stem cells transfected with the C361Y-FGFR2 point mutation in conjunction with an in vitro mechanical tensile stress model to elucidate the aberrant osteogenic differentiation patterns under mechanical stimulation. The study identifies PIEZO1, a mechanosensitive ion channel protein, as a pivotal mediator in transducing extracellular mechanical signals. Through integrated analysis of PIEZO1-modulated HIPPO/YAP and BMP2/SMAD2 signaling cascades, the authors systematically evaluate the expression patterns of key regulatory nodes within these pathways. These findings establish a molecular framework for understanding defective osteogenic differentiation mechanisms in periosteal stem cells derived from Crouzon syndrome models, offering novel insights into potential therapeutic targets.

Craniosynostoses are congenital conditions characterized by premature suture fusions, altering skull growth and potentially impairing neurological function. Apert and Crouzon syndromes, both linked to FGFR2 mutations, share features but differ in their patterns of suture fusion and cranial deformation. This study quantitatively analyzes, with a high‐resolution 3D morphometric analysis, global cranial morphology in syndromic craniosynostoses, comparing Crouzon and Apert syndromes to controls using standard medical CT scans; 72 unoperated patients with syndromic craniosynostoses (51 with Crouzon syndrome, 21 with Apert syndrome) and 289 controls were analyzed. Cranial vault segmentation was performed, and surfaces were rigidly aligned. Non‐rigid registration enabled standardized mesh generation, with semi‐landmarks extracted for shape analysis. Age‐related shape variation was mitigated before analysis identified key morphological variation axes. Statistical comparisons revealed significant shape differences. Apert patients displayed a distinct turricephalic vault morphology with increased cranial height and reduced width, whereas Crouzon patients were more variable, with a moderate brachycephalic shape in bicoronal fusion and reduced vault distortion in pansynostosis. Unsupervised clustering showed clear morphometric separation of Apert patients, while Crouzon patients exhibited greater heterogeneity. Subgroups within Crouzon syndrome revealed specific deformation patterns associated with suture closure configurations. These findings refine our understanding of cranial shape variations in syndromic craniosynostoses and emphasize the need for integrating advanced morphometric analyses into clinical assessments. The distinct morphological signatures identified in Apert syndrome and Crouzon syndrome subgroups could inform personalized surgical planning and enhance phenotypic–genotypic correlations.

Differential impact of Crouzon and Apert syndromes on upper airways morphology: implications for Obstructive Sleep Apnoea.

The cranial base and midface characteristics in apert and Crouzon syndrome: A 3-dimensional analysis of morphological variations.

Osteogenic Distraction with RED Device and Lefort III Osteotomy in Patient with Crouzon Syndrome

Lefort 3 Distraction in Crouzon Syndrome: Insights, Successes, and Challenges