Correlation analysis of airway-facial phenotype in Crouzon syndrome by geometric morphometrics: A promising method for non-radiation airway evaluation.

AIM: This study aimed to verify the correlation of the airway-facial phenotype and visualize the morphological variation in Crouzon syndrome patients. Additionally, to develop a non-radiation methodology for airway assessments. METHOD: In this study, 22 patients diagnosed with Crouzon syndrome (Age: 7.80 ± 5.63 years; Gender distribution: 11 females and 11 males) were analysed. The soft tissue surface and airway were three-dimensionally reconstructed, and the entire facial phenotype was topologized and converted into spatial coordinates. Geometric morphometrics was employed to verify the correlation and visualize dynamic phenotypic variation associated with airway volume. A total of 276 linear variables were automatically derived from 24 anatomical landmarks, and principal component analysis (PCA) identified the 20 most significant parameters for airway evaluation. Correlation analyses between parameters and airway volume were performed. Then, patients were classified into three groups based on airway volume, and the differences among the groups were compared for evaluating the differentiating effectiveness of parameters. RESULTS: The facial phenotype was strongly correlated with the airway (coefficient: 0.758). Morphological variation was characterized by (i) mandibular protrusion and anticlockwise rotation; (ii) midface retrusion; (iii) supraorbital frontward and (iv) lengthening of the facial height. All the anthropometric parameters were strongly associated with the airway, and the differences among the groups were statistically significant. CONCLUSION: This study confirmed the strong correlation between facial phenotype and airway parameters in Crouzon syndrome patients. Despite the development of the airway, pathological midface retrusion was still aggravated, suggesting that surgical intervention was inevitable. Three-dimensional facial anthropometry has potential as a non-radiation examination for airway evaluation.

Synchondrosis fusion contributes to the progression of postnatal craniofacial dysmorphology in syndromic craniosynostosis.

Syndromic craniosynostosis (CS) patients exhibit early, bony fusion of calvarial sutures and cranial synchondroses, resulting in craniofacial dysmorphology. In this study, we chronologically evaluated skull morphology change after abnormal fusion of the sutures and synchondroses in mouse models of syndromic CS for further understanding of the disease. We found fusion of the inter-sphenoid synchondrosis (ISS) in Apert syndrome model mice (Fgfr2S252W/+ ) around 3 weeks old as seen in Crouzon syndrome model mice (Fgfr2cC342Y/+ ). We then examined ontogenic trajectories of CS mouse models after 3 weeks of age using geometric morphometrics analyses. Antero-ventral growth of the face was affected in Fgfr2S252W/+ and Fgfr2cC342Y/+ mice, while Saethre-Chotzen syndrome model mice (Twist1+/- ) did not show the ISS fusion and exhibited a similar growth pattern to that of control littermates. Further analysis revealed that the coronal suture synostosis in the CS mouse models induces only the brachycephalic phenotype as a shared morphological feature. Although previous studies suggest that the fusion of the facial sutures during neonatal period is associated with midface hypoplasia, the present study suggests that the progressive postnatal fusion of the cranial synchondrosis also contributes to craniofacial dysmorphology in mouse models of syndromic CS. These morphological trajectories increase our understanding of the progression of syndromic CS skull growth.

Unravelling the pathogenesis of foramen magnum stenosis in patients with severe achondroplasia: a CT-based comparison with age-matched controls and FGFR3 craniosynostosis syndromes.

OBJECTIVE: Foramen magnum(FM) stenosis can be responsible for acute and chronic damage to the cervicomedullary junction in children with achondroplasia. The bony anatomy and patterns of suture fusion of the FM in this context are incompletely understood, yet becoming increasingly important in the light of novel medical therapies for achondroplasia. The objective of this study was to describe and quantify bony anatomy and fusion patterns of FM stenosis in patients with achondroplasia using CT scans, comparing them to age-matched controls and other FGFR3 craniosynostosis patients. METHODS: Patients with achondroplasia and severe FM stenosis, classified as achondroplasia foramen magnum score(AFMS) grades 3 and 4, were identified from a departmental operative database. All had pre-operative CT scans of the craniocervical junction. Measurements obtained comprised sagittal diameter (SD), transverse diameter (TD), foramen magnum area, and opisthion thickness. Anterior and posterior interoccipital synchondroses (AIOS and PIOS) were graded by the extent of fusion. These measurements were then compared with CT scans from 3 age-matched groups: the normal control group, children with Muenke syndrome, and children with Crouzon syndrome with acanthosis nigricans (CSAN). RESULTS: CT scans were reviewed in 23 cases of patients with achondroplasia, 23 normal controls, 20 Muenke, and 15 CSAN. Children with achondroplasia had significantly smaller sagittal diameter (mean 16.2 ± 2.4 mm) compared to other groups (control 31.7 ± 2.4 mm, p < 0.0001; Muenke 31.7 ± 3.5 mm, p < 0.0001; and CSAN 23.1 ± 3.4 mm, p < 0.0001) and transverse diameters (mean 14.3 ± 1.8 mm) compared with other groups (control 26.5 ± 3.2 mm, p < 0.0001; Muenke 24.1 ± 2.6 mm, p < 0.0001; CSAN 19.1 ± 2.6 mm, p < 0.0001). This translated into a surface area which was 3.4 times smaller in the achondroplasia group compared with the control group. The median grade of the AIOS fusion achondroplasia group was 3.0 (IQR 3.0-5.0), which was significantly higher compared with the control group (1.0, IQR 1.0-1.0, p < 0.0001), Muenke group (1.0, IQR 1.0-1.0, p < 0.0001), and CSAN (2.0, IQR 1.0-2.0, p < 0.0002). Median PIOS fusion grade was also highest in the achondroplasia group (5.0, IQR 4.0-5.0) compared with control (1.0, IQR 1.0-1.0, p < 0.0001), Muenke (2.5, IQR 1.3-3.0, p < 0.0001), and CSAN (4.0, IQR 4.0-4.0, p = 0.2). Distinct bony opisthion spurs projecting into the foramen magnum were seen in achondroplasia patients but not others, resulting in characteristic crescent and cloverleaf shapes. CONCLUSION: Patients with AFMS stages 3 and 4 have significantly reduced FM diameters, with surface area 3.4 times smaller than age-matched controls. This is associated with premature fusion of the AIOS and PIOS in comparison with controls and other FGFR3-related conditions. The presence of thickened opisthion bony spurs contributes to stenosis in achondroplasia. Understanding and quantifying bony changes at the FM of patients with achondroplasia will be important in the future quantitative evaluation of emerging medical therapies.

Crouzon's Syndrome with a Dominant Sinus Pericranii Draining Transverse Sinus: Report of a Rare Association and Review of Literature.

INTRODUCTION: Crouzon's syndrome and sinus pericranii (SP) are rare entities. Only few cases having both the features are reported. SP most commonly drains in relation to superior sagittal sinus and their communication to major posterior dural sinuses is rare. CASE REPORT: We report a rare case of Crouzon's syndrome with SP at a suboccipital location with termination of left transverse sinus into the SP draining further through the extracranial suboccipital and extravertebral cervical venous plexi into external jugular veins. Distal transverse sinus and sigmoid sinus on the left side were absent. CONCLUSION: Crouzon's syndrome with SP is an extremely rare entity. SP with communication to major posterior dural venous sinuses is also rare and mostly associated with multi-suture craniosynostosis. Management depends on the volume of venous blood they are draining. Most of them are dominant type and their occlusion is not feasible. Preoperative diagnosis of a dominant SP is essential for proper surgical planning as it needs to be preserved mandatorily to prevent cerebral venous infarction.

Syndromic Craniosynostosis: Objective and Parent-Reported Outcome Measurements after Cranio-Facial Remodelling Surgeries.

INTRODUCTION: Syndromic craniosynostosis (SC) is a rare entity compared to the non-syndromic variant. Treatment involves a multidisciplinary approach towards a multitude of problems. Early intervention is known to be better for optimum results. We reviewed outcomes of children with SC who underwent reconstructive cranio-facial surgery. MATERIALS AND METHODS: A retrospective study was conducted using data from hospital case files and the picture archival communication system. Objective data like the cephalic index (CI), both preoperatively and post-operatively, were compared. Subjective data for the cosmesis outcome - "Sloan and Whitaker outcome class" - following surgery were assessed. Also, parent-reported outcome measurement (PROM) was performed with various parameters to assess quality of life (QOL). RESULTS: We had 21 operated cases of SC, with 19 needing cranio-facial remodelling. The male to female ratio was 11:10. Crouzon's syndrome was the most common syndromic association followed by Apert's syndrome. Nineteen patients underwent cranio-facial remodelling surgeries and 2 underwent the ventriculo-peritoneal shunt only - for raised intracranial pressure (ICP). Nine patients underwent cranial remodelling with fronto-orbital advancements, and 3 of these patients also received le-fort's type 3 osteotomy and advancement later. Ten patients underwent fronto-orbital advancement with parieto-occipital barrel-stave osteotomies. OUTCOMES: Improvement in the CI was maximum at the 6-month follow-up. Six (37.5%) cases had Sloan class 1 outcome, 9 (56.25%) had class 2 outcomes, and 1 patient had a class 6 outcome. Whitaker cosmesis outcomes - 14 out of 16 cases (87.5%) had Category 1 outcomes. PROM was assessed. All parents reported at least a moderate improvement in cosmesis following surgery. Out of 15 cases, 10 (66%) reported significant improvement, while 4 (26.6%) cases reported moderate improvement with respect to eye and visual problems. Four parents reported snoring as a significant problem even after surgery. Most parents felt that the children were doing well, attending regular school, and social well-being was normal and had an overall good QOL. CONCLUSIONS: SC cases may have a multitude of other problems like raised ICP, ophthalmological problems, poor intelligence, and cognition apart from cosmetic concerns. PROMs revealed good outcomes in terms of cosmesis, cognition, and ophthalmological and oral cavity-related problems. Significant improvement in overall QOL was seen in most patients following cranio-facial remodelling surgery.

Comprehensive management of Crouzon syndrome: A case report with three-year follow-up.

Crouzon syndrome is one of the most common craniosynostosis facial syndromes caused by a mutation in the fibroblast growth factor receptor 2 (FGFR2) gene. Less commonly, there is a mutation of the FGFR3 gene which results in Crouzon syndrome syndrome with acanthosis nigricans. It involves the premature fusion of sutures of the cranial vault, base, orbital and maxillary region. The clinical presentation of this congenital deformity depends on the pattern and timing of sutural fusion. The present report describes the features and management of this syndrome in an 18-year-old woman. The patient presented with a hypoplastic maxilla, deficient midface, exorbitism due to shallow orbits, severe crowding and bilateral crossbite. A multidisciplinary approach involving orthodontics and surgical intervention with distraction osteogenesis brought about marked improvement in the facial profile, occlusion and upper airway. The aesthetics and function were greatly enhanced, and the results were found to be stable at the end of three years.

Characterization of dental pulp stem cells isolated from a patient diagnosed with Crouzon syndrome.

Stem cells isolated from patients with rare diseases are important to elucidate their pathogeny and mechanisms to enable regenerative therapy. However, the mechanisms underlying tissue regeneration using patient-derived dental pulp stem cells (DPSCs) are unclear. In this study, we investigated the levels of mRNA and protein expression related to cellular differentiation of Crouzon syndrome patient-derived DPSCs (CS-DPSCs) with a Gly338Arg fibroblast growth factor receptor 2 mutation. Multipotency-related gene expression levels were equivalent in both healthy donor DPSCs and CS-DPSCs. CS-DPSCs showed higher osteocalcin (OCN) expression than healthy donor DPSCs. CS-DPSCs showed a lower increase in the rate of OCN expression among phorbol 12-myristate 13-acetate (PMA)-treated cells than healthy donor DPSCs compared with untreated control cells. CS-DPSCs showed a lower phosphorylation rate of p38 and p44/42 in PMA-treated cells than healthy donor DPSCs compared with untreated control cells. These results demonstrate that CS-DPSCs have higher OCN expression and lower PMA stimulation-responsiveness than healthy donor DPSCs.

Midface and upper airway dysgenesis in FGFR2-related craniosynostosis involves multiple tissue-specific and cell cycle effects.

Midface dysgenesis is a feature of more than 200 genetic conditions in which upper airway anomalies frequently cause respiratory distress, but its etiology is poorly understood. Mouse models of Apert and Crouzon craniosynostosis syndromes exhibit midface dysgenesis similar to the human conditions. They carry activating mutations of Fgfr2, which is expressed in multiple craniofacial tissues during development. Magnetic resonance microscopy of three mouse models of Apert and Crouzon syndromes revealed decreased nasal passage volume in all models at birth. Histological analysis suggested overgrowth of the nasal cartilage in the two Apert syndrome mouse models. We used tissue-specific gene expression and transcriptome analysis to further dissect the structural, cellular and molecular alterations underlying midface and upper airway dysgenesis in Apert Fgfr2+/S252W mutants. Cartilage thickened progressively during embryogenesis because of increased chondrocyte proliferation in the presence of Fgf2 Oral epithelium expression of mutant Fgfr2, which resulted in a distinctive nasal septal fusion defect, and premature facial suture fusion contributed to the overall dysmorphology. Midface dysgenesis in Fgfr2-related craniosynostosis is a complex phenotype arising from the combined effects of aberrant signaling in multiple craniofacial tissues.

Syndrome-related outcomes following posterior vault distraction osteogenesis.

PURPOSE: The most commonly occurring syndromic craniosynostoses are Apert syndrome, Crouzon syndrome, Pfeiffer syndrome, and Saethre-Chotzen syndrome. There is insufficient data regarding postoperative syndrome-related outcomes following the posterior vault distraction osteogenesis (PVDO) procedure, as well as data addressing whether or not additional procedures will be subsequently necessary to comprehensively treat children who undergo PVDO. Thus, the objective of this study is to describe and compare syndrome-related potential complications and outcomes associated with the PVDO procedure. METHODS: An observational retrospective study was performed on consecutive patients (n=24) with Apert syndrome, Crouzon syndrome, Pfeiffer syndrome, or Saethre-Chotzen syndrome, respectively, who underwent PVDO between 2012 and 2019. Demographic data (patient gender and age when the PVDO procedure was performed), diagnosis, surgery-related data, and outcome data (perioperative and midterm complications and need for additional surgery) were verified. RESULTS: Total relative blood transfusion volumes per kilogram for the patients were as follows: 22.75 ± 9.30 ml for Apert syndrome, 10.73 ± 2.28 ml for Crouzon syndrome (Apert versus Crouzon, p<0.05), 18.53 ± 8.08 ml for Pfeiffer syndrome, and 19.74 ± 9.12 ml for Saethre-Chotzen syndrome. None of the patients required a secondary procedure to alleviate intracranial pressure except for a Saethre-Chotzen patient. CONCLUSION: PVDO is an effective technique to address elevated intracranial pressure in SC patients that alleviates the need for secondary procedures at midterm follow-up. Apert syndrome patients presented relatively higher total blood transfusion rates than Crouzon syndrome patients who were operated on at a later age and weighed more.

Severe craniolacunae and upper and lower extremity anomalies resulting from Crouzon syndrome, FGFR2 mutation, and Ser347Cys variant.

Crouzon syndrome is a rare form of syndromic craniosynostosis (SC) characterized by premature fusion of the cranial and facial sutures, elevated intracranial pressure, varying degrees of ocular exposure due to exorbitism, and airway compromise caused by midface retrusion. Craniolacunae and upper and lower extremity anomalies are not frequently found in Crouzon syndrome. We present a girl with Crouzon syndrome caused by c.1040 C > G, p.Ser347Cys, a pathogenic mutation in the FGFR2 gene with atypical characteristics, including craniolacunae resembling severe Swiss cheese type of bone formation, and upper and lower extremity anomalies which are more commonly associated with Pfeiffer syndrome patients. Distinguishing between severe Crouzon syndrome patients and patients who have mild and/or moderate Pfeiffer syndrome can be challenging even for an experienced craniofacial surgeon. An accurate genotype diagnosis is essential to distinguishing between these syndromes, as it provides predictors for neurosurgical complications and facilitates appropriate family counseling related to long-term outcomes.

Perioperative airway complications in infants and children with Crouzon and Pfeiffer syndromes: A single-center experience.

BACKGROUND: Crouzon and Pfeiffer syndromes are rare genetic disorders characterized by craniosynostosis, exorbitism, and maxillary hypoplasia. Patients with these syndromes frequently require general anesthesia for various diagnostic and surgical procedures and may present a challenge to anesthetists with regard to airway management. AIMS: The primary aim of this study was to determine the incidence, timing, and management of perioperative upper airway obstruction in infants and children with Crouzon and Pfeiffer syndromes. The secondary aim was to determine the degree of difficulty in performing endotracheal intubation. METHODS: A retrospective review of 812 anesthetic encounters in 67 patients was conducted. The following were recorded: timing and management of episodes of perioperative upper airway obstruction, from induction of anesthesia to discharge from recovery, degree of difficulty with laryngoscopy using the Cormack-Lehane grading system and number of intubation attempts required, patient demographics, respiratory comorbidity, surgical procedure, and anesthetic airway management techniques. RESULTS: Upper airway obstruction at induction of anesthesia was very common, with an incidence of 31% (167/542 anesthetic encounters affecting 54 patients). In a quarter of these incidents, bag-valve-mask ventilation was challenging, but a laryngeal mask airway was almost always effective. Upper airway obstruction on emergence from anesthesia was less common, with an incidence of 2.7% (14/515 anesthetic encounters affecting 10 patients). Contributing factors included patient comorbidity (obstructive sleep apnea, nasal stenosis) and the nature of surgery (craniofacial or airway procedures). Intubation was rarely difficult in this cohort, with 85% of laryngoscopies rated Cormack-Lehane grade 1 or 2 (n = 373), and 89% of intubations successful on the first attempt (n = 306). CONCLUSIONS: Upper airway obstruction at induction of anesthesia is common in patients with Crouzon and Pfeiffer syndrome. These patients are likely to present some difficulties with perioperative airway management, especially bag-valve-mask ventilation, but rarely endotracheal intubation.

Disappointing results of spring-assisted cranial vault expansion in patients with Crouzon syndrome presenting with sagittal synostosis.

The aim of this study was to report on a single center's experience with spring-assisted cranial vault expansion (SAE) in patients with Crouzon syndrome and sagittal suture synostosis. Strip craniotomy with SAE has resulted in successful outcomes with low complication and revision rates in patients with isolated scaphocephaly. However, recent experience suggests that outcomes in patients with Crouzon syndrome and sagittal synostosis (SS) who undergo SAE are less favorable compared with the outcomes of those who undergo frontobiparietal (FBP) expansion. The authors reviewed both operations performed at a single center and noticed an upward expansion of the skull, which may be related to ventriculomegaly, with concurrent intracranial hypertension and poor aesthetic outcome. All patients diagnosed with Crouzon syndrome and SS who were treated with SAE required a revision FBP operation. Based on this outcome, the authors consider Crouzon syndrome a contraindication for correcting SS with springs.

Midface distraction osteogenesis using a modified external device and 3D virtual simulation: technical note.

INTRODUCTION/BACKGROUND: Distraction osteogenesis (DO) with an external distraction device such as the rigid external distraction frame has become an established method for treating midface hypoplasia in faciocraniosynostosis. It allows for greater advancement of the midface in comparison with traditional Le Fort III osteotomies, associated or not with fronto-orbital osteotomies (Le Fort IV). However, the forward movement of the bone segments may not always be performed obeying an ideal distraction vector, resulting in asymmetries, anterior open bite, and loosening of screws. In addition, the cost of the distraction devices is significant and may preclude their routine use in developing countries. METHOD: We present an alternative device and method for craniofacial advancement in a clinical case of Crouzon's syndrome. RESULTS: A 3D virtual simulation of the distraction vector and a modified external device were used in the current case. CONCLUSION: The alternative external device in this case proved to be safe, effective, and reliable.

Comparison of Pain Perception in Patients Affected by Cleft and Cranio Facial Anomalies Treated With Traditional Fixed Appliances or Invisalign.

INTRODUCTION: The objective of this prospective study was to compare the difference in pain perception between treatment with aligners (AL) and fixed appliances (FA) in patients affected by cleft and craniofacial anomalies (CFA). METHODS: The sample consisted of 100 syndromic caucasian patients affected by various CFA from 2 different hospitals. Fifty patients treated with AL were matched for sex, age, and CFA with a control sample of 50 patients treated with FA. A modification of the Mc Gill Pain Questionnaire was adapted to our needs. RESULTS: Statistical differences were found. Aligners induced more tightness and tension than FA, while FA induced more pain descriptors and patients reported a higher intake of painkillers. CONCLUSIONS: The results of this study documented a higher pain perception with FA than with AL in patients affected by CFA. The higher sensitivity to pain in cleft and craniofacial patients with fixed treatment could be related to their higher prior sensitization, given the past surgeries and orthodontic treatments. Thus, this study might suggest that Invisalign treatment might be a further interesting treatment option for patients with cleft in order to reduce their burden of orthodontic pain.

Successful management of anesthesia complications in a child with Crouzon syndrome.

Crouzon syndrome (CS) is a rare autosomal dominant inherited disorder caused by mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. The disease is characterized by premature fusion of the coronal and sagittal sutures of the skull, resulting in clinical manifestations of midfacial hypoplasia, shallow orbit, maxillary dysplasia, and occasional upper respiratory obstruction. This article presents the case of a child aged 2 years and 7 months with CS scheduled for bilateral tonsillectomy and adenoidectomy. The patient had a difficult procedure of extubation and was reintubated and the tracheal intubation was removed 2 days after surgery. The CS is a rare condition with physical characteristics that can result in difficult airway manipulation. It is important for anesthesiologists to recognize and avoid potential airway complications in the management of such patients through detailed preoperative evaluation and careful observation after surgery to reduce perioperative risks.

[Advances in research on Crouzon syndrome and related ophthalmic complications].

Crouzon syndrome is an autosomal dominant disorder characterized by acrocephaly, exophthalmos, hypertelorism, strabismus, parrot-beaked nose, and hypoplastic maxilla. It is usually caused by a pathogenic mutation in the fibroblast growth factor receptor 2 gene and premature fusion of the sutures of the cranium and the base of the skull. This article documents the ophthalmic complications in patients with Crouzon syndrome before and after the influence of craniofacial surgery with particular emphasis on the different mechanisms and treatments involved. It is important to perform timely decompressive surgery before the presence of optic atrophy and corneal defects, and make early detection and adequate management of amblyopia, ptosis and strabismus. (Chin J Ophthalmol, 2020, 56: 544-548).

Evolution of the phenotype of craniosynostosis with dental anomalies syndrome and report of IL11RA variant population frequencies in a Crouzon-like autosomal recessive syndrome.

In 2011, biallelic loss-of-function variants in the interleukin receptor 11 alpha gene IL11RA were found to be associated with a Crouzon-like craniosynostosis syndrome with associated dental anomalies (CRSDA). Since then, a total of 41 similar patients have been reported with IL11RA variants. We report two adult brothers diagnosed with Crouzon syndrome as children, in which the clinical diagnosis of CRSDA was made on reevaluation. Laboratory testing detected biallelic IL11RA variants, c.916_924dup (p.Thr306_Ser308dup) and c.781C > T (p.Arg261Cys), both of which have now been reported in other families. Protein modeling and conservation analysis show that these two mutation sites cluster together near a WSXWS motif that likely plays a significant role in regulating IL11RA protein function. Population analysis from gnomAD shows that Non-Finnish Europeans (similar to ethnicity of this family), have an allele frequency for p.Thr306_Ser308dup of 0.014% and p.Arg261Cys of 0.008%. We found other ethnicities have functional IL11RA missense variants at higher frequencies. With this report, we provide a summary of the clinical findings including details of middle ear anomalies associated with conductive hearing loss. We also provide data supporting the populations at risk for this condition to increase recognition and diagnosis of this rare autosomal recessive craniosynostosis syndrome.

Inherited FGFR2 mutation in a Chinese patient with Crouzon syndrome and luxation of bulbus oculi provoked by trauma: a case report.

BACKGROUND: Crouzon syndrome (CS), which results from fibroblast growth factor receptor 2 mutations, is associated with craniosynostosis, exophthalmos, and other symptoms. Herein, we report the genetic abnormalities detected in a Chinese family with autosomal dominant CS, combined with luxation of the eyeball. This luxation was a consequence of the trauma to the shallow orbits. CASE PRESENTATION: The proband was a 4-year-old boy. He accidentally fell, following which luxation of the bulbus oculi occurred immediately. Computed tomography and magnetic resonance imaging clearly revealed ocular proptosis. Upon physical examination, the proband, his father, and grandfather had ocular proptosis, shallow orbits, and mid-face hypoplasia. However, their hands and feet were clinically normal. Genomic DNA was extracted from the peripheral blood through a polymerase chain reaction performed for the target sequence. Genetic assessments revealed a heterozygous missense mutation (c.1012G > C, p.G338R) in exon 10 of the human FGFR2, cosegregated with the disease phenotype in this family. These findings confirmed the diagnosis of CS. DISCUSSION: CS is usually caused by FGFR2 mutations. While there are a few reports of luxation of the bulbus oculi in Chinese families with CS, the ocular proptosis, shallow orbits, combined with luxation of eyeball after trauma observed in this patient were particularly interesting. Our findings enhance the current knowledge of traumatic luxation concomitant with CS.

Correlation between Papilledema and Intracranial Hypertension in Crouzon Syndrome: A Case Report and Review of the Literature.

Crouzon syndrome represents the most common syndromic craniosynostosis. Ocular complications are frequent, including papilledema and optic atrophy, often related to increased intracranial pressure (ICP). However, there is a poor correlation between ICP normalization and resolution of papilledema. We describe the case of a 6-month-old infant who presented with typical phenotypic features of Crouzon syndrome. Pre- and postoperative ICP monitoring was used. Papilledema persisted despite ICP improvement after decompressive craniectomy. Possible causes of papilledema in this syndromic craniosynostosis are discussed in light of the existing literature.

A Crouzon syndrome from the Classic period of Maya civilization?

This article describes a retrospective diagnosis through an artistic representation of a pre-Columbian Central America bowl figuring a child with clinical characteristics of Crouzon syndrome. The report also highlights the importance of icono-diagnosis for a better description of the existing diseases into ancient societies.