Crouzon Syndrome Research Articles

Anomalous venous collaterals in Apert and Crouzon syndromes and their relationship to ventricle size and increased intracranial pressure.

The exact association between the frequently present anomalous intracranial venous vasculature, emissary collaterals, ventriculomegaly, and increased intracranial pressure (ICP) in children with Apert and Crouzon syndromes remains an enigma. This study aimed to evaluate the association between the aberrant venous system and ventricle size and increased ICP, and to assess the development of the venous structures over time. This retrospective cohort study included all patients with Apert or Crouzon syndrome with available CT venography (CTV) scans of the brain. Anomalous venous vasculature was assessed by the total collateral score (TCS), which scored 9 intra- and extracranial venous structures (TCS range 0-16). Ventricle size (fronto-occipital horn ratio [FOHR]) was measured on the same scan. The presence of increased ICP, a shunt, tonsillar herniation, and head circumference were extracted from electronic patient records and were used as secondary covariates. Subsequent CTV scans were scored when available. Ninety patients were included in this study. The mean TCS was 7.5 ± 2.5, and was comparable for patients with Apert and Crouzon syndromes (mean 8.0 and 7.3, respectively). The presence of an extra abnormal venous structure was associated with an increase of the FOHR of 3.2% (p < 0.01). After dividing the venous structures into intra- and extracranial, a similar association between both and the FOHR was found (4.1% and 2.3%, respectively; p < 0.01). The TCS was similar for patients with normal and increased ICP at the time of the scan. Sixteen patients had dual CTV scans. The median time between both scans was 3.2 years. The presence of collaterals remained stable over time (median ΔTCS = 0.3). Seven patients with functioning shunts also maintained high TCSs (median TCS = 9). In patients with Apert and Crouzon syndromes, a close relationship between venous collaterals and ventricle size was observed, in which a more extensive aberrant venous drainage pattern, both intra- and extracranial, was associated with larger ventricles. Preliminary longitudinal data suggested that the presence of venous collaterals remained constant over time despite effective treatment of increased ICP, indicating reliance on these collaterals even in cases of normal ICP. The authors hypothesize that this dependence on collateral drainage is the result of their aberrant internal venous anatomy and predisposes individuals to increased ICP.

New CRISPR/Cas9-based Fgfr2C361Y/+ mouse model of Crouzon syndrome exhibits skull and behavioral abnormalities.

Crouzon syndrome (CS), a syndromic craniosynostosis, is a craniofacial developmental deformity caused by mutations in fibroblast growth factor receptor 2 (FGFR2). Previous CS mouse models constructed using traditional gene editing techniques faced issues such as low targeting efficiency, extended lineage cycles, and inconsistent and unstable phenotypes. In this study, a CRISPR/Cas9-mediated strategy was employed to induce a functional augmentation of the Fgfr2 point mutation in mice. Various techniques, including bone staining, micro-CT, histological methods, and behavioral experiments, were employed to systematically examine and corroborate phenotypic disparities between mutant mice (Fgfr2C361Y/+) and their wild-type littermates. Confirmed via PCR-Sanger sequencing, we successfully induced the p.Cys361Tyr missense mutation in the Fgfr2 IIIc isoform of the extracellular domain (corresponding to the p.Cys342Tyr mutation in humans) based on Fgfr2-215 transcript (ENSMUST00000122054.8). Fgfr2C361Y/+ mice exhibited characteristics consistent with the phenotypic features associated with CS, including skull-vault craniosynostosis, skull deformity, shallow orbits accompanied by exophthalmos, midface hypoplasia with malocclusion, and shortened skull base, notably without any apparent limb defects. Furthermore, mutant mice displayed behavioral abnormalities encompassing deficits in learning and memory, social interaction, and motor dysfunction, without anxiety-related disorders. Histopathological examination of the hippocampal region revealed structural abnormalities, suggesting possible brain development impairment secondary to craniosynostosis. In conclusion, we constructed a novel gene-edited Fgfr2C361Y/+ mice strain based on CRISPR/Cas9, which displayed skull and behavioral abnormalities, serving as a new model for studying genetic molecular mechanisms and exploring treatments for CS. KEY MESSAGES: CRISPR/Cas9 crafted a Crouzon model by enhancing Fgfr2-C361Y in mice. Fgfr2C361Y/+ mice replicate CS phenotypes-craniosynostosis and midface anomalies. Mutant mice show diverse behavioral abnormalities, impacting learning and memory. Fgfr2C361Y/+ mice offer a novel model for cranial suture studies and therapeutic exploration.

Visual Prognosis in Craniosynostosis Patients: A 20-year Retrospective Cohort Study at a Tertiary Referral Center in Thailand

Objective: This study aims to evaluate the visual prognosis in craniosynostosis patients in order to identify ophthalmologic manifestations in craniosynostosis patients and strabismus surgery outcomes in these patients. Materials and Methods: The medical record charts of craniosynostosis patients were reviewed retrospectively from January 2000 to June 2023. All the relevant patient data, such as age, sex, visual acuity, ophthalmologic examinations, and strabismus surgery outcomes were recorded. Results: In total, 123 patients were included in the study, among whom 65 (52.84%) were male. Overall, there were 70 cases (56.91%) of non-syndromic craniosynostosis, and 53 cases of syndromic craniosynostosis, comprising Crouzon syndrome (15 cases), Apert syndrome (8 cases), Pfeiffer syndrome (2 cases), and other syndromes (28 cases). The mean age at first examination was 3.11 years old. Out of 107 cases with visual impairment at the first visit, 92 (85.98%) showed no visual impairment at the last visit. Among the 87 patients with strabismus, 28 (32.18%) had strabismus at the primary position, with exotropia being the most common type (18 cases). Eight cases underwent strabismus surgery, and 4 cases achieved success (deviation &lt; 10 prism diopters). Other ophthalmologic manifestations were lagophthalmos, exposure keratopathy, ptosis, proptosis, and nasolacrimal duct obstruction. Conclusion: Among the craniosynostosis cases, 85.98% had no visual impairment, with the common ophthalmologic manifestations being refractive errors, strabismus, lagophthalmos, and exposure keratopathy. The syndromic craniosynostosis cases showed worse visual outcomes and a higher incidence of ocular diseases than non-syndromic cases. The success rate for strabismus surgery in craniosynostosis patients was 50%.

Optic Nerve Head Morphological Variation in Craniosynostosis: A Cohort Study

To evaluate optic nerve head morphology in children with craniosynostosis versus healthy controls. Single-centre, prospective cohort study METHODS: Handheld optical coherence tomography (OCT) was performed in 110 eyes of 58 children (aged 0-13 years) with craniosynostosis. Inclusion criteria were as follows: normal intracranial pressure (ICP) on invasive overnight monitoring, or clinically stable ICP. The latter was defined as stable VA within 1 logMAR line and no papilloedema on fundoscopy for at least four months following OCT, and normal/stable visual evoked potentials. Control data for 218 eyes of 218 children were obtained from a published normative dataset. The main outcome measures were disc width, cup width, rim width and retinal nerve fibre layer (RNFL) thickness (nasal and temporal). Outcome measures were compared using three-way linear mixed model regression analysis (FGFR 1/2-associated craniosynostosis, non-FGFR 1/2-associated craniosynostosis, and controls). Out of 63 eligible children with craniosynostosis, handheld OCT imaging was successful in 110 eyes of 58 children (92%). Of these, 22 (38%) were female. Median subject age at OCT examination was 53 months (range: 2 to 157; IQR: 39 to 73). Twelve children (21%) had FGFR1/2-associated syndromes (Crouzon, n=6; Apert, n=4; Pfeiffer, n=2). Control data were available for 218 eyes of 218 healthy children. 122 controls (56%) were female. Median control age at OCT examination was 20 months (range: 0 to 163; IQR: 6 to 59). When comparing optic nerve head morphology in craniosynostosis (n=58) versus controls (n=218), disc width was 6% greater (p=0.001), temporal cup width was 13% smaller (p=0.027), rim width was 16% greater (p<0.001) and temporal RNFL was 11% smaller (p=0.027). When comparing FGFR1/2-associated syndromes (Crouzon, Apert and Pfeiffer syndromes, n=12) to the rest of the craniosynostosis group (n=46), disc width was 10% smaller (p=0.014) and temporal cup width was 38% smaller (p=0.044). This cohort demonstrated morphological differences of the optic nerve head in craniosynostosis, most markedly in Crouzon, Apert and Pfeiffer syndromes. These findings could help improve ophthalmological monitoring and surgical decision-making in children with craniosynostosis. Further work on longitudinal optic nerve head changes in syndromic and non-syndromic craniosynostosis would be valuable.

Latent disentanglement in mesh variational autoencoders improves the diagnosis of craniofacial syndromes and aids surgical planning

Background and objective:The use of deep learning to undertake shape analysis of the complexities of the human head holds great promise. However, there have traditionally been a number of barriers to accurate modelling, especially when operating on both a global and local level. Methods:In this work, we will discuss the application of the Swap Disentangled Variational Autoencoder (SD-VAE) with relevance to Crouzon, Apert and Muenke syndromes. The model is trained on a dataset of 3D meshes of healthy and syndromic patients which was increased in size with a novel data augmentation technique based on spectral interpolation. Thanks to its semantically meaningful and disentangled latent representation, SD-VAE is used to analyse and generate head shapes while considering the influence of different anatomical sub-units. Results:Although syndrome classification is performed on the entire mesh, it is also possible, for the first time, to analyse the influence of each region of the head on the syndromic phenotype. By manipulating specific parameters of the generative model, and producing procedure-specific new shapes, it is also possible to approximate the outcome of a range of craniofacial surgical procedures. Conclusion:This work opens new avenues to advance diagnosis, aids surgical planning and allows for the objective evaluation of surgical outcomes. Our code is available at github.com/simofoti/CraniofacialSD-VAE.

Using A Disentangled Neural Network to Objectively Assess the Outcomes of Midfacial Surgery in Syndromic Craniosynostosis.

Advancements in artificial intelligence and the development of shape models that quantify normal head shape and facial morphology provide frameworks by which the outcomes of craniofacial surgery can be compared. In this work, we will demonstrate the use of the Swap Disentangled Variational Autoencoder (SD-VAE) to objectively assess changes following midfacial surgery. Our model is trained on a dataset of 1405 3D meshes of healthy and syndromic patients which was augmented using a technique based on spectral interpolation. Patients with a diagnosis of Apert and Crouzon syndrome who had undergone sub- or trans-cranial midfacial procedures utilising rigid external distraction were then interpreted using this model as the point of comparison. A total of 56 patients met our inclusion criteria, 20 with Apert and 36 with Crouzon syndrome. By using linear discriminant analysis to project the high-dimensional vectors derived by SD-VAE onto a 2D space, the shape properties of Apert and Crouzon syndrome can be visualised in relation to the healthy population. In this way, we are able to show how surgery elicits global shape changes in each patient. To assess the regional movements achieved during surgery, we use a novel metric derived from the Malahanobis distance to quantify movements through the latent space. Objective outcome evaluation, which encourages in-depth analysis and enhances decision making, is essential for the progression of surgical practice. We have demonstrated how artificial intelligence has the ability to improve our understanding of surgery and its effect on craniofacial morphology.

Cranial bone microarchitecture in a mouse model for syndromic craniosynostosis.

Crouzon syndrome is a congenital craniofacial disorder caused by mutations in the Fibroblast Growth Factor Receptor 2 (FGFR2). It is characterized by the premature fusion of cranial sutures, leading to a brachycephalic head shape, and midfacial hypoplasia. The aim of this study was to investigate the effect of the FGFR2 mutation on the microarchitecture of cranial bones at different stages of postnatal skull development, using the FGFR2C342Y mouse model. Apart from craniosynostosis, this model shows cranial bone abnormalities. High-resolution synchrotron microtomography images of the frontal and parietal bone were acquired for both FGFR2C342Y/+ (Crouzon, heterozygous mutant) and FGFR2+/+ (control, wild-type) mice at five ages (postnatal days 1, 3, 7, 14 and 21, n = 6 each). Morphometric measurements were determined for cortical bone porosity: osteocyte lacunae and canals. General linear model to assess the effect of age, anatomical location and genotype was carried out for each morphometric measurement. Histological analysis was performed to validate the findings. In both groups (Crouzon and wild-type), statistical difference in bone volume fraction, average canal volume, lacunar number density, lacunar volume density and canal volume density was found at most age points, with the frontal bone generally showing higher porosity and fewer lacunae. Frontal bone showed differences between the Crouzon and wild-type groups in terms of lacunar morphometry (average lacunar volume, lacunar number density and lacunar volume density) with larger, less dense lacunae around the postnatal age of P7-P14. Histological analysis of bone showed marked differences in frontal bone only. These findings provide a better understanding of the pathogenesis of Crouzon syndrome and will contribute to computational models that predict postoperative changes with the aim to improve surgical outcome.

Optic nerve elongation during fronto-facial surgery for Crouzon syndrome: 3D quantification and clinical implications.

Fronto-facial monobloc advancement with internal distraction (FFMBA) is a key procedure in the management of syndromic craniosynostoses. FFMBA involves circumferential dissection and linear enlargement of the orbit, potentially leading to mechanical stress on the optic nerve (ON). Several reports of transient vision loss during the distraction process led us to investigate ON shape modifications during facial advancement, with the aim to potentially refine current clinical guidelines on postoperative management and the distraction schedule. Twenty-six patients with Crouzon syndrome were included in this study. ONs were segmented on pre- and postoperative CT scans. Distraction amplitudes, linear and curved lengths, and cross-section diameters of the ON were assessed along the main axis of the nerve. A two-level hierarchical multivariate linear model was used to screen for factors associated with ON morphology. The mean age at FFMBA was 4.4 ± 3.8 years. Two patients presented with transient impaired vision during distraction. The final mean fronto-orbital and temporo-zygomatic distraction amplitudes were 18 ± 4 mm and 18 ± 6 mm, respectively. At the end of distraction, ONs were elongated (+1.8 mm for curved lengths, p = 0.013), and their mean cross-section was reduced (-1.9 mm2, p < 0.001) in the proximal intraorbital portion (first 15 mm). In the 2 patients with visual symptoms, functional impairment was associated with ON area reduction (OR 0.487, p < 0.001) and increased temporo-zygomatic distraction amplitude (OR 2.240, p < 0.001). ON was elongated during FFMBA, with proximal diameter reduction. Transient visual impairment with normal fundus examination during distraction seemed to have a morphological basis, based on 2 cases. These results suggest the importance of vision monitoring associated with fundus examination during distraction, and advocate for early extubation after FFMBA to allow clinical follow-up.

Mystery of the Muenke midface: spheno-occipital synchondrosis fusion and craniofacial skeletal patterns.

The spheno-occipital synchondrosis (SOS) is an important site of endochondral ossification in the cranial base that closes prematurely in Apert, Crouzon, and Pfeiffer syndromes, which contributes to varying degrees of midface hypoplasia. The facial dysmorphology of Muenke syndrome, in contrast, is less severe with low rates of midface hypoplasia. We thus evaluated the timing of SOS fusion and cephalometric landmarks in patients with Muenke syndrome compared to normal controls. Patients with Muenke syndrome who had at least one fine-cut head computed tomography scan performedfrom 2000 to 2020 were retrospectively reviewed. A case-control study was performed of patient scans and age- and sex-matched control scans. SOS fusion status was evaluated as open, partially closed, or closed. We included 28 patients and compared 77 patient scans with 77 control scans. Kaplan-Meier analysis demonstrated an insignificantly earlier timeline of SOS fusion in Muenke syndrome (p = 0.300). Mean sella-orbitale (SO) distance was shorter (44.0 ± 6.6 vs. 47.7 ± 6.7 mm, p < 0.001) and mean sella-nasion-Frankfort horizontal (SN-FH) angle was greater (12.1° ± 3.8° vs. 10.1° ± 3.2°, p < 0.001)in the Muenke group, whereas mean sella-nasion-A point (SNA) angle was similar and normal (81.1° ± 5.7° vs. 81.4° ± 4.7°, p = 0.762). Muenke syndrome is characterized by mild and often absent midfacial hypoplasia, with the exception of slight retropositioning of the infraorbital rim. Interestingly, SOS fusion patterns in these patientsare not significantly different from age- and sex-matched controls despite an increased odds of fusion. It is possible that differences in timing of SOS fusion may manifest phenotypically at the infraorbital rim rather than atthe maxilla.

Early posterior vault distraction osteogenesis changes the syndromic craniosynostosis treatment paradigm: long-term outcomes of a 23-year cohort study

BackgroundEarly surgical management of syndromic craniosynostosis varies widely between centers, with patients typically undergoing multiple intracranial procedures through childhood. This study evaluates the long-term impact of early posterior vault distraction osteogenesis (PVDO) versus conventional treatment paradigms on the number and timing of subsequent craniofacial procedures.MethodsWe retrospectively analyzed the longitudinal operative patterns of patients with syndromic craniosynostosis treated from 2000 to 2023 with greater than five years of follow-up. Outcomes of patients who underwent early PVDO and conventional vault reconstruction were compared.ResultsFifty-five patients met the inclusion criteria (30 PVDO and 25 conventional). Age at initial vault surgery was similar between the PVDO and conventional cohorts (7.6 vs. 8.8 months), as were baseline craniometrics (p > 0.05). Multiple fronto-orbital advancement (FOA) procedures were performed in only 1/30 (3%) PVDO-treated patient versus 12/25 (48%) conventionally-treated patients (p < 0.001). Twelve (40%) PVDO-treated patients did not undergo FOA at all. Among patients with Apert and Crouzon syndromes, fewer PVDO-treated patients required FOA prior to midface surgery (33% vs. 92%, p = 0.004) or repeat FOA (6% vs. 50%, p = 0.005) compared to conventionally-treated patients. Among patients with Muenke and Saethre–Chotzen syndromes, a similar proportion of patients required FOA in the PVDO and conventional cohorts (91% vs. 100%, p = 0.353), though no PVDO-treated patients required repeat FOA (0% vs. 44%, p = 0.018).ConclusionsEarly PVDO is associated with a reduction in the high burden of both FOA and, critically, revisionary frontal procedures which are commonly seen in conventionally-treated patients with syndromic craniosynostosis.

Crouzon syndrome - Acase report

The autosomal dominant trait that causes Crouzon syndrome is inherited. A rare genetic disorder called Crouzon syndrome may show symptoms at birth or in early childhood. In most infants with Crouzon syndrome, the fibrous connection between some of the skull bones closes early. Trigonocephaly, scaphocephaly and brachecephaly are the consequences of premature closure. In certain cases, the disease does not run in the family of those affected.

Adenoidectomy in a child with Crouzon syndrome complicated with severe obstructive sleep apnea: Case report and review of literature.

Crouzon syndrome is an extremely rare craniofacial dysplasia, which is mainly caused by the early ossification and closure of the coronal suture of the skull. Craniofacial deformities can cause stenosis of the nasal cavity and posterior nasal meatus, resulting in sleep apnea. A 9-year-old boy with sleep snoring for 6 years, progressive aggravation in the past 1 month and accompanied by apnea during sleep. This case was diagnosed with Crouzon syndrome complicated with severe obstructive sleep apnea and severe hypoxemia. After adenoidectomy, he was admitted to the pediatric intensive care unit with ventilator-assisted respiration. During this period, the blood oxygen saturation fluctuated greatly. After trying to extubate, the blood oxygen was difficult to maintain and had to be intubated again. After active treatment, extubation was successful. The wound of nasopharynx recovered well and the sleep state was significantly improved 3 months postoperation. It is suggested that the time of ventilator-assisted breathing should be prolonged and the perioperative airway management should be strengthened in order to reduce the risk of postoperative complications.

Practical Considerations in Computerized Surgical Planning for Frontofacial Surgery.

The field of frontofacial surgery has advanced considerably, building on the pioneering techniques of Paul Tessier, with computerized surgical planning (CSP) emerging as a critical component. CSP has enhanced the precision and efficiency of surgeries for craniofacial dysostoses and hypertelorism, resulting in improved outcomes. This review delves into the importance of understanding orbital anatomy and the crucial bony and soft tissue landmarks essential to the application of CSP in frontofacial procedures, encompassing Le Fort III and monobloc advancements, as well as the correction of hypertelorism.

Anomalies of the Mesenchyme (Meninges and Skull)—Defects of Neural Tube Closure: Cephalocele and Other Calvarial and Skull Base Defects; Intracranial Lipomas; Arachnoid Cysts; Nonsyndromic and Syndromic Craniosynostoses

AbstractWithin the embryonic head, a layer of mesenchyme envelops the brain beneath the surface ectoderm. This cranial mesenchyme is responsible for the formation of the meninges, the calvaria (upper portion of the skull), and the scalp's dermis. Irregular development of these structures, particularly the meninges and the calvaria, is associated with notable congenital defects in humans, such as defects in neural tube closure. Anencephaly is the most common neural tube defect (NTD) and one of the most severe malformations of the central nervous system; it consists in the complete or partial absence of the brain, associated with the absence of the bones of the cranial vault. Iniencephaly is an uncommon congenital NTD characterized by abnormalities in the occipital region, including rachischisis of the cervicothoracic spine and a fixed retroflexion deformity of the head. Unlike anencephaly, in iniencephaly, there is a skull cavity and a normal-looking skin that entirely covers the head and the medullary retroflex area. Cephaloceles are congenital abnormalities distinguished by the protrusion of meninges and/or brain tissue through a naturally occurring defect in the skull bone. This anomaly is typically covered by skin or mucous membrane. Intracranial lipoma is a relatively uncommon and generally benign tumor that occurs in an abnormal location within the brain; it probably represents a disturbance of the differentiation of the primordial meninges: for unknown causes, the meningeal mesenchyme can differentiate into adipose tissue. Arachnoid cysts are sacs filled with cerebrospinal fluid (CSF) situated between the brain or spinal cord and the arachnoid membrane. Typically, these cysts originate within CSF cisterns and gradually expand their boundaries. Craniosynostosis is the early fusion of one or more cranial sutures. It can occur spontaneously, be associated with a syndrome, or have a familial connection. It can involve one or multiple cranial sutures. Pfeiffer's, Crouzon's, and Apert's syndromes are among the more prevalent syndromic craniosynostoses.

Construction of a Lentiviral Vector for Fgfr2 Overexpression and its Impact on the Biological Behavior of Cranial Suture Mesenchymal Stem Cells.

Suture mesenchymal stem cells (SuSCs), possessing self-renewal and multilineage differentiation abilities, play a crucial role in cranial bone growth. However, the impact of the disease-causing fibroblast growth factor receptor 2 (FGFR2) mutation on SuSCs in Crouzon syndrome has not been explored. This study aims to employ a lentivirus to overexpress Fgfr2 and investigate its role in the pathogenesis of Crouzon syndrome. Starting with the prevalent FGFR2 mutation site in patients with Crouzon syndrome, a lentiviral vector carrying the Fgfr2.C361Y mutation was developed and transfected into SuSCs, with a determined multiplicity of infection values. The experimental group, SuSCs+Fgfr2.C361Y, was compared with the empty vector and normal SuSC groups. Cell proliferation, cycle, apoptosis, and osteogenic functionality were assessed using CCK-8 assays, flow cytometry, ALP activity assays, and real-time quantitative polymerase chain reaction. The lentiviral vector effectively infected SuSCs, leading to heightened Fgfr2 expression, with optimal multiplicity of infection values of 80. The experimental group demonstrated decreased proliferation activity and a higher apoptosis rate compared with controls (P < 0.05). After osteogenic induction, the experimental group showed significantly higher ALP activity than controls (P < 0.05). Real-time quantitative polymerase chain reaction indicated lower mRNA expression levels of Gli1, Axin2, Pcna, Cdk2, and Bcl-2 in the experimental group than controls, whereas Bax, Runx2, and Bmp-2 showed higher expression (P < 0.05). This study constructed a lentivirus vector to upregulate Fgfr2 expression in SuSCs, suppressing stem cell stemness by inhibiting proliferation, promoting apoptosis, and accelerating premature osteogenic differentiation, resulting in premature suture closure. These findings establish the groundwork for further understanding the pathogenesis of Crouzon syndrome.

Three-dimensional quantification of soft tissue changes and its relationship to skeletal changes after Le Fort III, monobloc, and facial bipartition in syndromic craniosynostosis

To determine the effect of midface surgery on soft tissue changes and their relationship to hard tissue changes in patients with syndromic craniosynostosis. A retrospective analysis of patients who had undergone Le Fort III (LFIII), monobloc (MB), or facial bipartition (FB) was conducted. A 3D soft tissue mesh was generated from the preoperative scan and registered to the postoperative scan, after which the advancement was visualised. A total of 68 patients were included: 28 had undergone LFIII, 27 MB, and 13 FB. The included diagnoses were Apert (n = 23), Crouzon (n = 34), and craniofrontonasal syndrome (n = 11). After LFIII, most soft tissue advancement was seen around subnasale and pronasale (mean 15.1 ± 5.9 mm and 14.7 ± 5.7 mm, at age 7–12 years). After MB, a greater hard tissue than soft tissue advancement was seen for most landmarks, showing a high positive correlation. In patients undergoing FB without distraction (n = 10), mean preoperative inter-canthal distance was 48.9 mm, this reduced by 6.9 mm postoperatively. This study provides a comprehensive overview of the outcomes after midface surgery using 3D quantification for a better understanding of the soft tissue changes and their relationship to hard tissue changes.

Postural balance in the comprehensive rehabilitation of adolescents with cleft lip and palate and maxillofacial anomalies: A literature review

BACKGROUND: Patients with cleft lip and palate experience significant jaw relationship disorders and pathological bite formation, leading to changes in the motor activity of chewing muscles and postural balance disturbances. Most studies on postural control are conducted on patients with skeletal dentofacial anomalies and deformities without cleft lip and palate. The state of postural balance in children with cleft lip and palate requiring long-term complex medical rehabilitation, including bone-reconstructive operations on the jaw bones, remains poorly understood.&#x0D; AIM: To analyze publications dedicated to the evaluation of postural balance in adolescents with cleft lip and palate combined with jaw relationship disorders and pathological bite formation.&#x0D; MATERIALS AND METHODS: The article includes an analysis and review of several studies that investigated the state of postural balance in adolescents with cleft lip and palate, particularly at the final stages of growth and formation of the musculoskeletal system. Scientific articles published in various medical journals, monographs, dissertations, and materials from scientific symposiums related to this topic were used in the literature review. PubMed, Medline, Scopus, Web of Science, and RSCI were searched without language restrictions. The search depth was 23 years, and 64 studies were selected.&#x0D; RESULTS: The article analyzes literature data related to theories of the mechanism of mutual influence between postural balance and the dentofacial apparatus (disorders and pathological bite formation). The state of postural balance is influenced by various factors, including the craniosacral system and anomalies of the cervical spine. Patients with cleft lip and palate, hemifacial microsomia, and other craniofacial dysostoses with growth disorders of jaw bones experience an imbalance in the entire “descending” chain, causing postural disturbances, increased plantar pressure, increased foot rigidity, and changes in photogrammetry indicators, which should be considered when developing an individual rehabilitation program for these patients. The treatment of these patients without considering postural balance disorders can lead to temporomandibular joint pathologies, unstable results of the conservative orthodontic treatment of bite pathologies, and bone-reconstructive operations on jaws.&#x0D; CONCLUSIONS: The study highlights the ways of adaptation of the musculoskeletal system in the presence of occlusal relationship disorders and emphasizes the need to evaluate this influence comprehensively for the treatment of these patients. The limitations of the presented studies should be emphasized: insufficient sample size, lack of control groups and prospective studies, limited types of examination, and lack of studies dedicated to more severe anomalies of craniofacial development.

Thirty-year Experience Treating Syndromic Craniosynostosis: Long-term Outcomes Following Cranial Expansions.

Children with syndromic craniosynostosis require multiple cranial expansion procedures. The purpose of this study was to determine how many expansions are typically performed through maturity, to assess complication rates, and to identify trends that might reduce the burden of care. A retrospective chart review was performed of all consecutive patients undergoing cranial vault enlargement procedures for syndromic craniosynostosis by a single surgeon. Of 444 patients treated with Apert or Crouzon/Pfeiffer syndromes, 348 had complete long-term records. The mean age at last follow up was 16.9 years. Initial cranial expansions were performed at a significantly younger age for those beginning care at outside centers: 7.7-months versus 25.7-months in Dallas. 26.4% had ventriculoperitoneal shunts (syndrome-specific incidences: Apert 16%, Crouzon 27%, Pfeiffer 54%). Of 498 procedures, 80% were anterior, 18% posterior, and 2% were mid-vaults. The overall complication rate was 2%, with no differences found between anterior and posterior procedures. Those treated solely in Dallas underwent a mean of 1.9 expansions. Children with Pfeiffer syndrome underwent more expansions (2.7) than those with Apert or Crouzon syndromes. Factors correlationing with more expansions included: earlier surgical interventions, use of distraction, venticuloperitoneal shunts, and treatment begun at outside centers (3.1 procedures). Children with syndromic craniosynostosis treated at a single center underwent an average of 2 skull expansion procedures with a 2% complication rate. Calvarial distraction, ventriculoperitoneal shunts, and earlier surgical interventions, were all associated with higher numbers of expansion procedures. Further research is needed to determine if these correlations are causal.

Alterations in Sphenoid Anatomy in Craniosynostosis: Implications for Fronto-Orbital Advancement.

Fronto-orbital advancement involves removal of the fronto-orbital bandeau. Visualization of the saw blade is lost as it passes through the fronto-orbital-sphenoid junction (FOSJ), placing the temporal lobe at risk of injury. We aim to provide a 3D analysis of the space surrounding this osteotomy to differentiate various types of craniosynostoses. Retrospective cohort. Institutional. Thirty patients with isolated unicoronal synostosis, nonsyndromic bicoronal synostosis, metopic synostosis, Apert syndrome, Crouzon syndrome, and Muenke syndrome. CT scans conducted between 2 months to 2 years of age were 3D reconstructed to compare craniometrics against normal controls. Craniometrics. The mean bone thickness of the FOSJ at the level of the supraorbital rim was significantly small for the Apert, unicoronal and bicoronal groups. The mean vertical height of the middle cranial fossa from the lesser sphenoid wing was significantly greater in the unicoronal group. The mean vertical height of the tip of the temporal lobe from the lateral sphenoid ridge was greater in the unicoronal, isolated bicoronal, and Apert groups. The mean corneal protrusion beyond the lateral orbital rim was significantly greater in the Apert and unicoronal groups. The mean horizontal depth of the orbit was smallest in the Apert group. The mean vertical distance between the dacryon and the foramen cecum, and the mean volume of temporal lobe beneath the sphenoid shelf were the largest in the Apert group. Patients with Apert syndrome have the most unfavorable morphology of the anterior and middle cranial fossae.

A girl with synostotic plagiocephaly: unfolding as rare case

Dysmorphic head shape can be a presenting complaint of craniosynostosis which needs to be investigated in detail for any genetic or syndromic associations. Many genetic mutations have been associated with craniosynostosis but ERF gene mutation has been found to be very rare. Here, we have discussed about an 8 years old girl who presented with dysmorphic head shape. She had crouzoid features like exorbitism, malar hypoplasia with copper beaten skull appearance and pansynostosis on CT Head but genetic evaluation revealed ERF gene mutation suggestive of craniosynostosis 4. She had short stature which was the unique association with it. Thus, high index of suspicion should be kept for craniosynostosis 4 when phenotypic features are suggestive of crouzon syndrome as crouzon syndrome can phenotypically mimic craniosynostosis with ERF gene mutation and genetic analysis should be done to look for alternate cause of craniosynostosis; especially to look for ERF gene mutation.