Long-Term Follow-Up of Apert Syndrome Following Mid-Face Advancement: More Than 3 Decades Later.

Apert syndrome is characterized by craniosynostosis, a hypoplastic mid-face, skeletal abnormalities, symmetric syndactyly of the hands and feet, and a degree of neurocognitive impairment. Long-term outcomes of patients who have undergone surgical correction of Apert syndrome are limited. The authors present the case of a 73-year-old female with Apert syndrome, with follow-up of more than 3 decades following a fronto-orbital advancement and Le Fort III advancement. Clinical and radiologic images demonstrate a degree of skeletal resorption and relapse that is likely unavoidable. This provides insight into the long-term skeletal stability and esthetic outcomes for patients with Apert syndrome.

VACTERL Association in Patients With Metopic Synostosis: Is There a Link?

VACTERL association is diagnosed based on the non-random co-occurrence of at least 3 out of 6 congenital malformations. The prevalence is thought to be less than 1 in 10,000 to 1 in 40,000. There is no known link between VACTERL association and metopic synostosis in the literature. There were 122 operated cases of metopic synostosis at our institution from 1999 to 2023, with a 2.3:1 male-to-female ratio. The authors describe the co-occurrence of VACTERL association and metopic synostosis in 3 female patients with no identifiable genetic variants. Given that VACTERL association is a diagnosis of exclusion, other rare syndromes were considered but ultimately excluded. This suggests that the co-occurrence of VACTERL association and metopic synostosis is a potentially rare finding, and underlying pathogenic variants are yet to be identified.

Heterozygous FGFR3 c.138G>A Mutation Presenting With Achondroplasia and Hemifacial Microsomia.

We present a case of a patient with achondroplasia, hemifacial microsomia and an fibroblast growth factor receptor3 c.138G>A mutation. An association between the 2 conditions has not been previously described, but there is biological plausibility that the etiology of the 2 conditions is linked.

Re-imagining early cloverleaf skull deformity management from front to back approach-30 years on.

The cloverleaf skull deformity remains among the most complicated craniofacial conditions to successfully manage. Many cases achieve largely unsatisfactory outcomes due to the requirement for frequent reoperation on the cranial vault and failure to deal with all the elements of the craniofaciostenosis in a timely fashion. Early cranial vault surgery without addressing the cranial base deformity and its attendant cerebrospinal fluid flow changes is invariably challenging and disappointing. A recent focus on the expansion of the posterior cranial vault as a primary procedure with the greater volume change allows a delay in fronto-orbital advancement and reduced need for repeat surgery. We herein describe three cases of complex multisuture craniosynostosis with cloverleaf skull deformity who underwent neonatal posterior cranial vault decompression along with foramen magnum decompression. Our report examines the safety and rationale for this pre-emptive surgical approach to simultaneously deal with the cranial vault and craniocervical junction abnormalities and thus change the early trajectory of these complex cases.

PEDOT coated microneedles towards electrochemically assisted skin sampling.

Skin sampling is a diagnostic procedure based on the analysis of extracted skin tissues and/or the observation of biomarkers in bodily fluids. Sampling using microneedles (MNs) that minimize invasiveness is gaining attention over conventional biopsy/blood lancet. In this study, new MNs for electrochemically assisted skin sampling are reported, specifically tailored for combined skin tissue biopsy and interstitial fluid (ISF) extraction. To overcome risks associated with using metal MNs, a highly electroactive, mechanically flexible, and biocompatible organic conducting polymer (CP) coated onto plastic is chosen as an alternative. Two different variants of doped poly(3,4-ethylenedioxythiophene) are coated on polymethyl methacrylate and used in combination as a MN pair with subsequent testing via a variety of electrochemical techniques to (i) give real-time information of the MN penetration depth into the skin, and (ii) yield new information on various salts present in the ISF. The MN skin sampler shows the ability to extract ions from the hydrated excised skin as a step towards in vivo ISF extraction. The presence of ions was analyzed using X-ray photoelectron spectroscopy. This added chemical information in conjunction with the existing biomarker analysis increases opportunity for disease/condition detection. For example, in the case of psoriasis, information about salt in the skin is invaluable in combination with pathogenic gene expression for diagnosis.

Measuring the Change in Soft Palate Length and Shape Following Maxillary Advancement: A Cohort Study in Patients with Orofacial Clefts.

OBJECTIVE: To evaluate a method of measuring the change in palatal length and shape following maxillary advancement using synchronous lateral videofluoroscopy and voice recording in order to understand how movement of the maxilla may affect VPI risk in patients with cleft lip and/or palate (CL/P). DESIGN: Retrospective cohort study of children with cleft lip and/or palate. SETTING: Single center, tertiary children's hospital. PARTICIPANTS: Patients with cleft lip and/or palate who underwent maxillary advancement between 2016-21 inclusive. INTERVENTIONS: Maxillary advancement surgery, including those who underwent concurrent mandibular procedures. MAIN OUTCOME MEASURES: The length of the soft palate and the genu angle were measured throughout palatal dynamic range. Pre- and post-operative measurements were compared using a one sided T-test, with subgroup analysis for patients with clinical VPI. RESULTS: Ten patients were examined. The mean distance of maxillary advancement was 10.5 mm. The average increase in pre-genu soft palate length was 2.8 mm in the resting position and 2.9 mm in the closed position. The genu angle decreased in the closed position by 16.3 degrees. CONCLUSIONS: The soft palate showed limited ability to lengthen following maxillary advancement and this may explain the risk of VPI. There was partial compensation by the muscle sling of the palate as demonstrated by a more acute post-operative genu angle and this suggests one reason for the variability of VPI reported. Future research is required to investigate how length and shape changes measured using this method can predict VPI risk.

Metopic and Sagittal Craniosynostosis in Williams Syndrome.

Craniosynostosis has been previously reported in patients with Williams syndrome. Due to the associated significant cardiovascular anomalies, with an attendant increased risk of death under anaesthesia, most patients have been managed conservatively. Here we report the multidisciplinary approach in a 12-month-old female infant with Williams syndrome who has metopic and sagittal craniosynostosis. The child successfully underwent calvarial remodelling procedures, with the clinical outcome demonstrating dramatically improved global development after surgery.

Early bone reformation after cranial vault remodelling for sagittal craniosynostosis: A retrospective 3D analysis.

This study aims to measure postoperative bone reformation percentage, rates and patterns after cranial vault remodelling (CVR) in isolated non-syndromic sagittal craniosynostosis. Volumetric bone measurements were performed starting from the DICOM files of previously available postoperative CT scans. The 3D images were then resampled into the master box, and 'Skull 3D models' were derived. The percentage of bone reformation was investigated using automated 3D analysis software. The intra-rater reliability analysis revealed high reliability (Intraclass correlation coefficient = 0.99, p < 0.001). The median bone reformation volume and rate were 11.2 ml and 1.98 ml/week, respectively. The median percentage of bone reformation was 56.7% when the median postoperative CT timing was 6.1 weeks. As a statistic model, the linear plateau showed the highest Pseudo R2 in both volume and percentage of bone reformation predicting patterns. By using the calculated model at 9 weeks postoperatively, the re-osteogenesis reaches 80% of the total cranial defect. After CVR, the early bone reformation pattern was demonstrated as a linear plateau model rather than logarithmic. This study gives a better understanding of the pattern and quantity of re-osteogenesis at cranial defects after CVR. The statistic model can facilitate healthcare practitioners to predict bone reformation and improve postoperative care protocol in sagittal craniosynostosis management.

Facial Fractures in Indigenous and Non-indigenous Populations of South Australia.

INTRODUCTION: Maxillofacial trauma in indigenous populations is complex with sociocultural factors, access to health care, and poorer general health issues that impact outcomes. Assaults and road traffic accidents are disproportionately experienced by indigenous persons compared with non-indigenous. METHODS: A retrospective review was conducted from January 2012 to January 2017 at the Women and Children's Hospital and Royal Adelaide Hospital, Adelaide. All maxillofacial fractures that attended or were referred to the unit were included in this study. The primary objective was to analyze epidemiological trends of facial fractures and clinical outcomes in the South Australian indigenous and non-indigenous populations. RESULTS: Maxillofacial fractures in indigenous persons were less than in non-indigenous (31.2 versus 38.2 y, P < 0.001) with 3.8 odds of a facial fracture. Assault was 2.9 times more likely to result in a facial fracture, falls 40.9% less likely, and sports 29.4% less likely compared with non-indigenous ( P < 0.001). Alcohol-related facial fractures had significantly higher rates [odds ratio (OR = 3.8)] compared with non-indigenous. Indigenous from most disadvantaged areas and very remote areas also had significantly higher odds of a facial fracture. Indigenous persons had higher operative rates (OR = 2.8), postoperative complications (OR = 3.1), and a 3.7-day mean difference for the length of stay (6.6 versus 2.9 d, P < 0.001). CONCLUSIONS: Indigenous people are more likely to experience facial fractures from assault resulting in mandibular fractures, whereas non-indigenous people are likely to have sport or fall-related midface fractures. Young indigenous women from outer regional and very remote areas have greater odds of facial fractures caused by assault and alcohol with higher operative rates, postoperative complications, and extended length of stay.

Patterns and characteristics of maxillofacial fractures in women.

PURPOSE: Facial trauma in women is complex with physical, psychosocial, and cultural influences impacting clinical presentations. Although multifactorial, assaults and falls are principally reported as the main causes. METHODS: A retrospective review was conducted from January 2012 to January 2017 at the Women and Children's Hospital and Royal Adelaide Hospital, Adelaide. All maxillofacial fractures in women that attended or were referred to the unit were included in this study. The primary objective was to analyse epidemiological trends of facial fractures and clinical outcomes in the South Australian female population. RESULTS: There is a bimodal distribution of facial fractures at 25-35 years and 65 + years. Indigenous females were 19.5 years younger than non-indigenous females (30.5 vs 49.9, P < 0.001). Approximately half the cohort had a fall-related facial fracture, followed by assault (26.2%), and sports (10.3%). There was a higher proportion of non-alcohol-related trauma from assaults than alcohol-related assaults (72.5% vs 27.5%, P < 0.001). Over half (58.0%) of the cohort had a midface fracture. The elderly had increased odds of 1.9 fold for facial fractures in winter, largely from falls, compared to younger women. Associated injuries were present in almost half the elderly women with 2.6 times the risk compared to younger women. Younger women had higher incidences of surgical intervention (52.6% vs 14.3%, P < 0.05). CONCLUSIONS: Young women disproportionately experience larger incidences of non-alcohol-related assaults requiring operative intervention of the mandible, whereas elderly women principally suffer fall-related facial fractures with higher rates of associated injuries.

Multisuture craniosynostosis: a case report of unusual presentation of chromosome 14q32 deletion.

Multisuture craniosynostosis is associated with a number of syndromes and underlying gene mutations. It is rarely caused by chromosome disorders. For the management, multisuture craniosynostosis raises concerns about abnormal head shape and risks of increased intracranial pressure in affected patients. Calvarial reconstruction to reshape the skull shape and expand the intracranial volume plays an essential role in correcting particular problems. Here, we report a 2-month-old female infant presenting with low birth weight, abnormal head shape, dysmorphic facies and pinnae, hypotonia, and feeding difficulty. Three-dimensional computed tomographic scans revealed left unicoronal and sagittal synostoses. Chromosome microarray analysis revealed de novo chromosome 14q32.12-q32.31 deletion. Among the deleted genes, YY1 and BCL11B are the most likely candidate genes causing craniosynostosis. Some clinical features of the patient are similar to Temple syndrome indicating that the deleted region is paternal in origin. In summary, this is a rare case of chromosome 14q32 deletion with multisuture craniosynostosis. We also report the multidisciplinary management and clinical outcomes after early cranial vault remodelling procedures.

Characterization of an advanced viable bone allograft with preserved native bone-forming cells.

Bone grafts are widely used to successfully restore structure and function to patients with a broad range of musculoskeletal ailments and bone defects. Autogenous bone grafts are historically preferred because they theoretically contain the three essential components of bone healing (ie, osteoconductivity, osteoinductivity, and osteogenicity), but they have inherent limitations. Allograft bone derived from deceased human donors is one alternative that is also capable of providing both an osteoconductive scaffold and osteoinductive potential but, until recently, lacked the osteogenic component of bone healing. Relatively new, cellular bone allografts (CBAs) were designed to address this need by preserving viable cells. Although most commercially-available CBAs feature mesenchymal stem cells (MSCs), osteogenic differentiation is time-consuming and complex. A more advanced graft, a viable bone allograft (VBA), was thus developed to preserve lineage-committed bone-forming cells, which may be more suitable than MSCs to promote bone fusion. The purpose of this paper was to present the results of preclinical research characterizing VBA. Through a comprehensive series of in vitro and in vivo assays, the present results demonstrate that VBA in its final form is capable of providing all three essential bone remodeling properties and contains viable lineage-committed bone-forming cells, which do not elicit an immune response. The results are discussed in the context of clinical evidence published to date that further supports VBA as a potential alternative to autograft without the associated drawbacks.

Secondary Surgery in Metopic Craniosynostosis: Outcomes in a Tertiary Care Craniofacial Center in Australia.

ABSTRACT: Metopic craniosynostosis is a condition in which the metopic suture is prematurely fused. Trigonocephaly and hypotelorism are the major abnormal findings associated with synostosis. Fronto-orbital advancement with cranial remodelling procedure is the widely practised method for correction of the deformities. Previously, a few studies have shown a low incidence of secondary raised intracranial pressure after the primary surgery. Thus, we reviewed our database to investigate the outcomes of metopic craniosynostosis treatment between 1999 and 2020 in Cleft and Craniofacial South Australia. One hundred twelve patients (77 males and 35 females) with metopic synostosis were operated. The mean age of primary surgery was 11.1 months (range 2.8-131.7 months). Ten patients (9%) who had secondary raised intracranial pressure underwent secondary surgery. Among those, the mean age of primary and secondary surgery were 5.4 and 57.1 months, respectively. Syndromic patients were significantly revealed to have a higher incidence of secondary raised intracranial pressure. There were three patients (2.7%) who had other secondary procedures (hardware removal and aesthetic contouring procedures). This cohort identified a higher incidence of secondary raised intracranial pressure requiring secondary surgery than previous studies. Syndromic patients were significantly related to secondary raised intracranial pressure. The patients who had raised intracranial pressure tended to have primary correction at younger age. Long-term multidisciplinary follow-up is mandatory. The demand for secondary surgery for metalwork complications or cosmetic contouring is uncommon.

A comparative analysis of associated injuries in the elderly and youth for facial fractures.

INTRODUCTION: High-velocity and high-impact forces can yield life-threatening injuries that are not only limited to the face but can involve other regions of the body. Associated injuries are more frequent in the elderly impacting management and outcomes. The primary objective was to study the association between associated injuries and age groups by identifying epidemiological trends and differences among the elderly and younger population. METHODS: A retrospective review was conducted from January 2012 to January 2017 at the Royal Adelaide Hospital, Adelaide. A comparative analysis for elderly and younger controls was assessed for associated injuries, etiology, management, and length of stay. RESULTS: There were 355 elderly and 1884 younger controls for the study. There were differences between gender, alcohol, socioeconomic status, type of facial fracture, mechanism of injury, and associated injuries (p<0.05). The elderly were 3.6 times more likely to have an associated injury compared to the younger cohort (p<0.05). Total limb injuries were 2.2 times more likely in the elderly compared to the younger cohort, and neurological related injuries were 2.7 times more likely (p<0.05). Neurological injuries were most frequent in fall-related injuries, limb injuries in RTA; and soft-tissue injuries for assault, sport, animal, and work (p<0.001). The elderly had longer hospital stays as compared with younger controls (p<0.05). CONCLUSIONS: Associated injuries are more frequent in the elderly and impact other bodily systems leading to a longer length of stay. In the assessment and management of facial trauma, anatomical and disciplinary boundaries may cross requiring interdisciplinary care.

Patterns of Mandibular Fractures in South Australia: Epidemiology, Treatment, and Clinical Outcomes.

INTRODUCTION: The mandible is one of the most common facial bones to be injured with great clinical variability across countries caused by assaults, road traffic accidents, and falls. METHODS: A retrospective review was conducted for adult mandibular fractures from January 2012 to January 2017 at the Royal Adelaide Hospital, Adelaide. Our aim was to describe epidemiological trends of mandibular fractures, differences for sex and age, and clinical outcomes. RESULTS: Five hundred sixty five adult patients presented with a mandibular fracture with a male predominance (4.5:1). The mean age was 34.2 years with men 11.9 years younger than females (32.0 versus 44.1 years, P   <  0.001). Assaults represented 58.2% of cases. A quarter of the cohort reported alcohol use. Assaults commonly resulted in angle and symphyseal fractures, whereas almost all falls and road traffic accident resulted in condylar or coronoid fractures. Young men were 1.9 times more likely to have mandibular fractures compared to women, whereas elderly men were 11.8% less likely ( P  < 0.001). The most common fracture was the angle (33.6%) and the angle/symphyseal (14.2%). Men were 2.5 times more likely to have surgery. The complication rate was 10.8% and the re-operative rate was 5.0%. Women had a significantly longer admission of 1.6 days compared to men (4.4 versus 2.8 days, P  = 0.003). CONCLUSIONS: Young men are more likely to have mandibular fractures from assaults and have surgery. Young women and elderly females are more likely to have animal and fall-related injuries resulting including in condylar fractures with associated injuries and extended length of stay.

Familial Pfeiffer Syndrome: Variable Manifestations and Role of Multidisciplinary Team Care.

Pfeiffer syndrome is one of the autosomal dominant craniofacial syndromes. Classical clinical manifestations are coronal suture synostosis causing brachycephaly, midface retrusion, airway compromise, broad thumbs, and toes. Pfeiffer syndrome type I (classic type) is associated with FGFR1 mutation. However, wide range of clinical manifestations, with and without craniosynostosis, have been reported. Here, we present a family of Pfeiffer syndrome across 3 generations with identical FGFR1: c.755C>G (p.Pro252Arg) mutation. Where the members of the youngest generation have no cranial involvement. Lastly, we propose a guideline management for familial Pfeiffer syndrome management.

Multi-suture craniosynostosis in c.1570C>T (p.Arg524Trp) mutated TRAF7: a case report.

Craniosynostosis is a condition of premature fusion of the cranial sutures. Multi-suture craniosynostosis has been found to be associated with a number of syndromes and underlying gene mutations. Tumour necrosis factor receptor-associated factors (TRAFs) are a family of adaptor proteins interacting with cell surface receptors or other signalling molecules. TRAF7 is one of the factors involved in multiple biologic processes, including ubiquitination, myogenesis and toll-like receptor signalling. Here, we report a child who presented with multi-suture craniosynostosis and had the uncommon c.1570C>T (p.Arg524Trp) variant of TRAF7.

The Impact of Lockout Laws on Maxillofacial Fractures in South Australia.

INTRODUCTION: Alcohol outlet density and unrestricted trading hours are strongly predictive of domestic and non-domestic assault rates, respectively. international studies report a strong male predominance for facial fractures. Harm minimization policies such as lockout laws have gained considerable attention to reduce accessibility of alcohol consumption and drinking patterns. METHODS: A retrospective review was conducted from January 2012 to January 2017 at the Women and Children's Hospital and Royal Adelaide Hospital, Adelaide. All maxillofacial fractures that attended or were referred to the unit were included in this study. The primary objective was to determine the impact of facial fracture presentations, particularly assaults, for the pre- and post-lockout periods. RESULTS: From 2012 to 2017, there was a 5.1% decrease in assaults per year ( P  = 0.002). Assaults increased by 11.7% for women and alcohol related assaults decreased by 10.2% for men ( P  < 0.05). Assault and alcohol related assault rates decreased by 9.3% and 10.5%, respectively, between lockout periods ( P  < 0.001). Comparative analysis between Adelaide and control (inner regional city) showed assaults decreased by 9.8% between lockout periods (51.2% versus 41.4%, P  < 0.001). Multivariate analysis showed alcohol, open reduction internal fixation and men were associated with a lower risk of assault related fractures, but women and night time presentations had a higher risk ( P  < 0.05). CONCLUSIONS: The influence of lockout laws contributed to an overall decrease in assaults and operative interventions, particularly alcohol related incidences amongst men. Ongoing longitudinal surveillance should guide current evidence for policy developers to reduce the risk of harm.