Search

Objectives/hypothesis: A tracheal cartilaginous sleeve (TCS) is a rare anomaly characterized by anterior fusion of tracheal cartilages. TCS is associated with syndromic craniosynostoses including Apert, Crouzon and Pfeiffer syndromes and FGFR2, FGFR3, and TWIST1 variants. This study presents a 30-year review of patients with syndromic craniosynostosis and TCS and describes diagnostic methods, genetic variants, surgical interventions, and long-term outcomes., Study Design: Retrospective, single-institution review., Methods: This review included patients with syndromic craniosynostosis and TCS treated at Seattle Children's Hospital from 1990 to 2020. Tracheostomy, genetic variants, and additional surgery were primary measures. Fisher's exact test compared need for tracheostomy in patients with proposed high-risk (FGFR2 p.W290 or FGFR2 p.C342) versus low-risk genetic variants., Results: Thirty patients with TCS were identified. Average age at diagnosis was 12 months (range 2-weeks to 7.9-years; standard deviation 19.8 months). Syndromes included Pfeiffer (37%), Apert (37%), and Crouzon (26%). Severe obstructive sleep apnea was present in 76% of patients. Tracheostomy was performed in 17 patients (57%); five were successfully decannulated. Additional interventions included adenotonsillectomy (57%), nasal (20%), laryngeal (17%), and craniofacial skeletal surgery (87%). All patients with Pfeiffer syndrome and FGFR2 p.W290C variants and 83% of patients with FGFR2 p.C342 variants required tracheostomy, differing from other variants (P = .02, odds ratio 33, 95% confidence interval 1.56-697.96). One patient (3%) died., Conclusion: TCS contributes to multilevel airway obstruction in patients with syndromic craniosynostosis. Genetic testing in patients with FGFR2-related syndromic craniosynostoses may identify those at risk of TCS and facilitate early intervention. A better understanding of this patient population may foster individualized airway management strategies and improve outcomes., Level of Evidence: 4 Laryngoscope, 132:215-221, 2022., (© 2021 The American Laryngological, Rhinological and Otological Society, Inc.)

Cloverleaf skull is a complex skull deformity named after its cloverleaf shape. The primary pathogenic factor is craniosynostosis. Craniosynostosis could result in limited development of skull, brain, maxillofacial and nervous system, thus arising a series of complex syndromes, including Crouzon, Apert, Pfeiffer, Saethre-Chotzen and Muenke syndromes. Craniosynostosis syndromes exhibit a group of similar symptoms because of the mutual cause, craniosynostosis, with Crouzon syndrome being the most common one. At present, the surgical approach for Craniosynostosis syndromes has been established and generally accepted, including a series of surgical interventions in stages according to patients' age, severity and function of skull malformation. It's a large, complex, long time span deformity correcting procedure with formidable limitations, including high risk, expensive cost, quantity shortage of qualified surgeons and unsatisfactory successful rate for complicated cases. Hence, a new nonsurgical therapy for patients with craniosynostosis syndromes is seriously needed. A concept of Dynamic Cranial Suture Management (DCSM) was introduced. It includes objective and evaluable monitoring tools and craniosynostosis patent modifying drugs or medications tools which consist of regulatory factors for osteoclasts, osteoblasts and mesenchymal stem cells. By using these tools alternatively in different skull developing stages, DCSM is designed to prevent craniosynostosis. A Crouzon syndrome case was also presented., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Craniosynostosis is the premature fusion of cranial bones. The goal of this study was to determine if delivery of recombinant tissue nonspecific alkaline phosphatase (TNAP) could prevent or diminish the severity of craniosynostosis in a C57BL/6 FGFR2C342Y/+ model of neonatal onset craniosynostosis or a BALB/c FGFR2C342Y/+ model of postnatal onset craniosynostosis. Mice were injected with a lentivirus encoding a mineral targeted form of TNAP immediately after birth. Cranial bone fusion as well as cranial bone volume, mineral content and density were assessed by micro CT. Craniofacial shape was measured with calipers. Alkaline phosphatase, alanine amino transferase (ALT) and aspartate amino transferase (AST) activity levels were measured in serum. Neonatal delivery of TNAP diminished craniosynostosis severity from 94% suture obliteration in vehicle treated mice to 67% suture obliteration in treated mice, p<0.02) and the incidence of malocclusion from 82.4% to 34.7% (p<0.03), with no effect on cranial bone in C57BL/6 FGFR2C342Y/+ mice. In contrast, treatment with TNAP increased cranial bone volume (p< 0.01), density (p< 0.01) and mineral content (p< 0.01) as compared to vehicle treated controls, but had no effect on craniosynostosis or malocclusion in BALB/c FGFR2C342Y/+ mice. These results indicate that postnatal recombinant TNAP enzyme therapy diminishes craniosynostosis severity in the C57BL/6 FGFR2C342Y/+ neonatal onset mouse model of Crouzon syndrome, and that effects of exogenous TNAP are genetic background dependent., Competing Interests: The authors have declared that no competing interests exist.

Freeman-Burian syndrome (FBS), formerly Freeman-Sheldon syndrome, is a complex myopathic craniofacial syndrome. Functional craniofacial deformities resulting in respiratory, eating, auditory, or speech impairments often are present to varying degrees in this unique population. There are few references in the literature addressing diagnosis, evaluation, operative counseling, and craniofacial management of FBS, and guidance was absent. As part of a clinical practice guideline development process for FBS, the authors have reviewed dental and oral health concerns, hearing loss, paranasal sinusitis, dysphagia, and dysphasia management for patients with FBS. Searching PubMed and Google Scholar has yielded 14 results describing dentofacial and otorhinolaryngologic concerns in FBS. There is a significant paucity of scholarship on FBS, presenting considerable knowledge gaps. Craniofacial muscles may be preferentially impacted by fibrous tissue replacement. The lack of available objective data should not reduce clinical vigilance to the possibility that fibrous tissue replacement may influence almost any aspect of the patient's presentation, thus necessitating nonstandard treatment deviations. Based on the decades of experience with this challenging patient population, the authors feel much can be done to afford patients with FBS a good and productive quality of life through exquisite medical surveillance, rapid intervention in acute upper respiratory disturbances, conservative operative intervention, and longitudinal lifestyle structuring by the patients.

For many, the experience of a complex craniofacial malformation condition, such as Freeman-Burian syndrome (FBS), formerly Freeman-Sheldon syndrome, is deeply distressing. There are few references in the literature addressing initial evaluation and operative counseling for FBS, and guidance is absent. Two major outcomes of FBS are explored, namely diagnostic accuracy and therapeutic result, to identify factors influencing optimal clinical care in (1) diagnosis, (2) evaluation, (3) general and craniofacial operative counseling, and (4) craniofacial management.PubMed searches have yielded 15 results describing craniofacial surgery in FBS and 29 manuscripts describing psychosocial aspects of surgery and patient and family counseling and education in other non-intellectually impairing craniofacial malformation conditions. Research in this area of scholarship is plagued by problems, especially considerable knowledge gaps and an absence of study data for operative outcomes. As a result, the literature remains unsettled, though our experience presents a much more clear picture of the clinical reality for this challenging patient population. While many challenges and limitations to treatment are present, much can be done to afford these patients a good and productive quality of life through operative intervention and longitudinal psychosocial support.

Background: Craniosynostosis is a developmental disorder characterized by the premature fusion of skull sutures, necessitating repetitive, high-risk neurosurgical interventions throughout infancy. This study used protein-releasing Titania nanotubular implant (TNT/Ti) loaded with glypican 3 (GPC3) in the cranial critical-sized defects (CSDs) in Crouzon murine model ( Fgfr2 c342y/+ knock-in mutation) to address a key challenge of delaying post-operative bone regeneration in craniosynostosis., Materials and Methods: A 3 mm wide circular CSD was created in two murine models of Crouzon syndrome: (i) surgical control (CSDs without TNT/Ti or any protein, n=6) and (ii) experimental groups with TNT/Ti loaded with GPC3, further subdivided into the presence or absence of chitosan coating (on nanotubes) (n=12 in each group). The bone volume percentage in CSDs was assessed 90 days post-implantation using micro-computed tomography (micro-CT) and histological analysis., Results: Nano-implants retrieved after 90 days post-operatively depicted well-adhered, hexagonally arranged, and densely packed nanotubes with average diameter of 120±10 nm. The nanotubular architecture was generally well-preserved. Compared with the control bone volume percentage data (without GPC3), GPC3-loaded TNT/Ti without chitosan coating displayed a significantly lower volume percent in cranial CSDs ( P <0.001). Histological assessment showed relatively less bone regeneration (healing) in GPC3-loaded CSDs than control CSDs., Conclusion: The finding of inhibition of cranial bone regeneration by GPC3-loaded TNT/Ti in vivo is an important advance in the novel field of minimally-invasive craniosynostosis therapy and holds the prospect of altering the whole paradigm of treatment for affected children. Future animal studies on a larger sample are indicated to refine the dosage and duration of drug delivery across different ages and both sexes with the view to undertake human clinical trials., Competing Interests: The authors declare no conflicts of interest in this work.

Palliation in pediatric otorhinolaryngology is a rarely discussed but important aspect of care. This review encapsulates current thinking on pediatric palliative care (PC) and demonstrates, through one case, the impact of integrating PC into clinical care. We encourage early consideration of pediatric palliative care approaches for children with complex otorhinolaryngologic disorders., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Craniofacial defect is a critical problem in dental clinic, which has a tremendous impact on patients' quality of life. Mesenchymal stem cell-based therapy has emerged as a promising approach for tissue defect repair. However, reduced survival after mesenchymal stem cells (MSCs) transplantation remains as a major problem in this area, which hampers the outcome of regeneration. Recently, the mechanism to mobilize endogenous MSCs for tissue regeneration has received increasing attentions, as it does not require exogenous cell transplantation. The primary goal of this study was to confirm the role of intravenous substance P in mobilizing endogenous CD45 - CD11b - CD29 + MSCs in critical-sized bone defect animals and to investigate the effects of substance P on calvarial bone repair. Flow cytometry analyses revealed that intravenous substance P promoted the mobilization of endogenous CD45 - CD11b - CD29 + MSCs after bone defect. In addition, Micro-CT showed that intravenous substance P improved the outcomes of calvarial bone repair. Furthermore, we discovered that systemic injection of substance P attenuated inflammation and enhanced the survival of the local-transplanted GFP + MSCs. Our findings suggested that substance P together with its mobilized CD45 - CD11b - CD29 + MSCs helped improve calvarial defect repair through regulating inflammatory conditions and promoting the survival of local-transplanted cells.

Crouzon syndrome with acanthosis nigricans (CAN) is caused by a mutation in the fibroblast growth factor receptor ( FGFR) 3 gene that presents clinically as Crouzonoid craniofacial features in association with other anomalies such as acanthosis nigricans and benign odontogenic tumors. Diagnosis through the use of genetic mutational analysis is critical, as it alerts the surgeon to the need for careful screening for jaw tumors so that timely treatment in the form of curettage or segmental resection can be provided.

Crouzon syndrome is an autosomal-dominant congenital disease due to a mutation in the fibroblast growth factor receptor 2 protein. The purpose of this study is to evaluate wound-healing potential of Crouzon osteoblasts and adipose-derived stem cells (ADSCs) in a murine model. Parietal skull defects were created in Crouzon and mature wild-type (WT) CD-1 mice. One group of WT and Crouzon mice were left untreated. Another group was transplanted with both WT and Crouzon adipose-derived stem cells. Additional groups compared the use of a fibrin glue scaffold and periosteum removal. Skulls were harvested from each group and evaluated histologically at 8-week and/or 16-week periods. Mean areas of defect were quantified and compared via ANOVA F-test. The average area of defect after 8 and 16 weeks in untreated Crouzon mice was 15.37 ± 1.08 cm and 16.69 ± 1.51 cm, respectively. The average area of the defect in untreated WT mice after 8 and 16 weeks averaged 14.17 ± 1.88 cm and 14.96 ± 2.26 cm, respectively. WT mice with autologous ADSCs yielded an average area of 15.35 ± 1.34 cm after 16 weeks while Crouzon mice with WT ADSCs healed to an average size of 12.98 ± 1.89 cm. Crouzon ADSCs transplanted into WT mice yielded an average area of 15.47 ± 1.29 cm while autologous Crouzon ADSCs yielded an area of 14.22 ± 3.32 cm. ANOVA F-test yielded P = .415. The fibroblast growth factor receptor 2 mutation in Crouzon syndrome does not promote reossification of critical-sized defects in mature WT and Crouzon mice. Furthermore, Crouzon ADSCs do not possess osteogenic advantage over WT ADSCs.

Purpose: Pediatric patients with Crouzon syndrome have great possibilities of suffering from obstructive sleep apnea (OSA), which is mainly due to midfacial hypoplasia and facial deformities. For most patients, a multidisciplinary and sequential treatment plan is necessary to make for Crouzon syndrome often has different phenotypes of different severity in OSA and facial deformities. Typical patients were selected in this paper to illustrate the necessity of individualized therapy for treating OSA., Methods: In this paper, we have introduced four Crouzon syndrome children of different severity in suffering from OSA and maxillofacial deformities. Detailed information was given including clinical manifestations, radiological findings, and polysomnography detections. Based on the above findings, different but effective treatment options for these children's OSA problems were adopted, either by surgeries including distraction osteogenesis and craniomaxillofacial surgeries with or without tonsillectomy or by noninvasive continuous positive airway pressure (CPAP) therapy., Results: Follow-up studies for more than 1 year showed problems of OSA and nocturnal hypoxia of those four patients were all alleviated greatly, as well as maxillofacial deformities. Combined with pre-operative and post-operative orthodontics, one patient also got optimal results in better facial profile and dental occlusion., Conclusion: Thus, based on adequate clinical evaluations and patients' conditions including age, disease severity, and esthetic considerations, individualized therapy should be made and performed carefully to obtain optimized results in treating OSA for pediatric Crouzon syndrome patients.

We describe two proof-of-concept trials of delayed non-operative therapy of multiple hand and wrist contractures in a woman with a severe expression of Freeman-Sheldon syndrome (FSS), at ages 24 and 28 years. Having presented as an infant to a university referral centre, passive correction was not accompanied by strengthening exercises, and correction was lost. FSS is described as a myopathic distal arthrogryposis; diagnosis requires the following: microstomia, whistling face appearance, H-shaped chin dimpling, nasolabial folds, and multiple hand and foot contractures. Spinal deformities, metabolic and gastroenterological problems, other craniofacial characteristics, and visual and auditory impairments, are frequent findings. To avoid possible FSS-associated complications of malignant hyperthermia and difficult intubation, and to reduce or eliminate need for surgery, we proceeded with passive manipulation without anaesthesia or sedation. We believe this is the first report of attempted non-operative correction of multiple hand and wrist contractures in an adult with FSS., (2015 BMJ Publishing Group Ltd.)

Crouzon syndrome is an autosomal dominant disorder with variable expressivity, characterized by skull and facial malformations. Such alterations vary from case to case. Management requires multidisciplinary approach. Two cases of two sisters affected by Crouzon syndrome are described. Treatment was performed by orthopedic and orthodontic devices without surgery. Good esthetics and functional results were obtained. Five-year follow-up records are presented.

Crouzon syndrome is a rare genetic disorder caused due to genetic mutations. It is characterised by partial hearing loss, dry eyes, strabismus and underdevelopment of the upper jaw with facial deformities and malocclusion. These facial deformities greatly affect the social and emotional development of the affected child. The present case report highlights the social problems faced by a child suffering with Crouzon syndrome.

Freeman-Sheldon syndrome is characterized by typical dysmorphic features of the face (microstomia with putting lips and H-shaped dimpling of the chin, giving the appearance of a whistling face) and symmetrical hands and feet defects (camptodactyly, joint contractures). The intelligence quotient is usually within the normal range. Mutations in the MYH3 gene at 17p13 have been shown to cause the syndrome, inherited as an autosomal dominant trait. Two patients with clinical diagnosis of Freeman- Sheldon syndrome, confirmed by molecular study were described in this article. Additionally, clinical aspects, differential diagnosis and genetic basis of the disease were described as well as medical problems concerning patients with Freeman-Sheldon syndrome were discussed such as anesthetic aspects, malignant hyperthermia and pulmonary complications after surgery. The authors highlight the significance of dysmorphic features in patients with developmental delay and congenital defects as well as indicate the role of multidisciplinary approach in the diagnostic and therapeutic process.

Tracheal cartilaginous sleeve (TCS) is a congenital malformation involving fusion of the tracheal arches that may be isolated to a few tracheal arches, include the entire trachea, or extend beyond the carina into the bronchi. Tracheotomy was required in 9 of 23 craniosynostosis cases undergoing gradual distraction at Osaka City General Hospital from March 2002 to April 2006. TCS was diagnosed in 5 of 9 cases-four Pfeiffer patients and one Crouzon patient. Diagnosis was made intraoperatively during tracheotomy or at autopsy. 3D-CT was not useful in diagnosing TCS. Aggressive management of respiratory infection and pulmonary secretion, selection of appropriate tracheostomy tubes, and endoscopic evaluation are very important to care in managing TCS patients.

Human skull is made up of many bone joints connected by sutures. The sutures fuse in later life after the complete growth of the brain. If any of these sutures closes early, it may interfere with the normal growth of the brain. The developing brain may exert pressure on the skull and may grow in the direction of the other open sutures. Premature sutural fusion may occur alone or together with other anomalies, making up various syndromes. Crouzons syndrome is an example of such a syndrome that is associated with premature synostosis of the sutures of the skull. Presented in this article is a case of Crouzons syndrome seen in a boy aged 9 years.

We report three paediatric cases of severe dehydration and hyponatraemia with circulatory compromise associated with the use of external ventricular drainage of cerebrospinal fluid. Two of the children had cardiac arrests. All were successfully resuscitated. While there were additional factors that contributed to other fluid losses, and fluid balance data are incomplete, these cases highlight a need for increased vigilance when managing children with external ventricular drains.

Background: In 1966 Ramfjord and Ash proposed the Michigan's splint that, at present, is one of the splints widely accepted for the treatment of craniomandibular disorders (CMD)., Methods: For this study, thirty-one subjects were examined according to the protocol of the European Academy of CMD; each patient indicated the intensity of pain using a Visual Analogue Scale (VAS). After therapy with Michigan's splint, the visit was repeated and the patient indicated again the VAS., Results: The results showed that the splint has short-term benefit effects on the muscular and articular pain, even if the effects are lesser on the articular pain., Conclusions: The Michigan's splint is a valid device for therapy of CMD, moreover it is very cheap, very easy to use and without contraindications.

We studied a group of children (aged 2.2-15 years) with craniofacial dysostosis and obstructive sleep apnoea to assess the use of nasal continuous positive airway pressure (n-CPAP) as a palliative form of treatment. A variable period of time was allowed for acclimatisation to n-CPAP (1 day to 2 months), depending on the patient. Patients were then admitted for their first CPAP trial. Baseline breathing difficulty and the effectiveness of n-CPAP were assessed by respiratory sleep studies. Successful results were obtained with n-CPAP in five of the eight patients, with marked clinical and polygraphic improvements of the respiratory pattern immediately after n-CPAP was established. Of the remaining three cases, one child needed a prolonged period of acclimatisation to the n-CPAP system, one was withdrawn from the study, and one failed to respond to n-CPAP and was found to have complete blockage of the upper airways as a result of enlarged adenoids. Our results confirm that n-CPAP can be tolerated even by young patients and can be effective, and that it may be a useful alternative palliative treatment for obstructive sleep apnoea in children with craniofacial syndromes.

Nager acrofacial dysostosis, first described by Nager and deReynier in 1948, is a rare syndrome characterized by mandibulofacial dysostosis with associated radial defects. The facial features include downward slanting palpebral fissures, absent eyelashes in the medial third of the lower lids, mandibular and malar hypoplasia, dysplastic ears with conductive deafness, and variable degrees of palatal clefting. Upper limb malformation is a constant feature of Nager syndrome and ranges from thumb hypoplasia to absence of the radial ray. The maxillo-mandibular hypoplasia and associated retroplaced tongue set the stage for early and significant upper airway obstruction. The craniofacial anomalies and associated trismus make emergent airway intubation challenging. We present a case of Nager syndrome with life threatening airway obstruction unresponsive to conservative management. This case and a review of the literature emphasize the importance of early tracheotomy for these patients.

Perthes' disease was seen in two boys, aged 6 1/2, with the Russell-Silver Syndrome. Both presented with groin or thigh pain in their shortened side together with a progressive limp. They were treated conservatively, and when reviewed 6 1/2 years after diagnosis the lesions of the hip had improved clinically and radiographically. The leg length discrepancy did not increase.

A standard method of treating syndromes with anomalies in the face does not exist. Not only are the differences between the symptoms of different syndromes very important. Also within one syndrome variations can be marked. A team of specialists supports the cranio-facial surgeon in his central role when treating these patients. Type of treatment, sequence, timing, et cetera, follow certain rules, which may be in part the same as for the treatment of 'ordinary' maxillo-mandibular disharmonies, but sometimes differ significantly from it. The most important aspects of treatment of three rather frequently seen cranio-facial syndromes are given. Incidence, symptoms, therapeutical possibilities and timing, and results are discussed as well as the necessity of this kind of surgery.

The purpose of this article was to enable the pediatrician to identify and understand the implications of common facial growth problems in children and adolescents. Problems with facial growth can result in aesthetic and functional complaints. Using a simple method of clinical evaluation, the pediatrician can identify facial growth problems in the anteroposterior, vertical, and transverse dimensions. These problems can then be referred for evaluation and treatment by a variety of means. By adopting a contemporary view that facial growth is the result of genetic and environmental factors (some of which are functional), growth modification becomes a real possibility. Unfortunately, some problems must be camouflaged or treated by combined surgical and orthodontic means. Continued growth in early adulthood can enhance or detract from treatment results obtained in childhood or adolescence. These dynamic properties of the face make management of facial growth challenging but generally rewarding and successful because of substantial aesthetic and functional improvements.

The symptoms of Silver-Russel syndrome are described using two cases. Special attention was paid to the development of the teeth and the jaws. The typical microretrognathism is accompanied by a frontal crowding especially in the lower jaw. It is possible to adjust it to a regular occlusion using functional orthopedic appliances. Noticeable is the high degree of caries in the first dentition. Paramorphiae are not ascertainable. Etiologically, the submucosal cleft palate, which was diagnosed for the first time, would suggest an intrauterine disturbance in the eighth to the tenth week of pregnancy.

An 8-year-old girl with Hallermann-Streiff syndrome (oculomandibulofacial syndrome) was examined. She had a history of severe snoring, reported nocturnal apnea, excessive daytime hypersomnolence, nocturnal enuresis, and failure to thrive. Overnight polysomnography confirmed severe obstructive sleep apnea. Long-term nasal continuous positive airway pressure (CPAP) therapy completely relieved the obstructive sleep apnea and was associated with improved weight gain and growth.

Historically, occlusal interferences are considered to be a major etiologic factor of craniomandibular disorders. Recent evidence suggests however that occlusal and articular parameters only play a minor etiologic role, if any. This controversy will only be solved after studies investigating well-defined homogenous patient groups. Concerning treatment, appliance therapy has proven to be a valuable part of the conservative reversible treatment procedure which allows to manage the majority of craniomandibular patients. Irreversible procedures e.g. complex orthodontic or prosthetic therapy, occlusal equilibration or surgery are only necessary in select cases and apply to very strict guidelines.

The author describes the clinical picture of mandibulofacial dysostosis and gives reasons for the necessity for early orthodontic treatment. Two examples are presented. The analysis of the case histories of a total of 10 patients with this syndrome showed that the responsiveness to functional orthodontic appliances is greatest in children with bilateral mandibulofacial dysostosis. The need for co-operation with other disciplines involved is pointed to.

The comprehensive management of Crouzon syndrome in a 14-year-old girl has been presented. Because of the complexity of the facial and associated problems, a multidisciplinary approach is necessary to provide maximum functional and esthetic results; however, with such a cooperative interdisciplinary effort, the improvement and benefits derived for these patients are rewarding to all concerned.

The treatment of Binder's maxillonasal dysostosis raises many problems and difficulties of both orthodontic and surgical natures. Orthodontic therapy should be conducted as early as possible and include, principally, an advancement of the maxilla by heavy extra-oral postero-anterior traction on an orthodontic mask. If good occlusion is obtained the patient can then be treated to improve the anatomical conditions of the muscles of the nose and upper lip. Maxillary, and more rarely mandibular osteotomies are indicated in cases with poor occlusion. When occlusion is reasonably good the hypoplasia has to be compensated for by using large portions of ilac bone to reconstruct the ridge and point of the nose. A preseptal graft on the ridge and secondarily, revisions of the point of the nose are often essential to ensure the best results.