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The Journal of Hand Surgery, European... May 2024This study evaluated how Apert hand syndactyly presentations and reconstructive techniques influence reconstruction outcomes. All cases at a major paediatric hospital...
UNLABELLED
This study evaluated how Apert hand syndactyly presentations and reconstructive techniques influence reconstruction outcomes. All cases at a major paediatric hospital between 2007 and 2022 were analysed, including 98 web space reconstructions in 17 patients. Overall, 62% of hands developed complications and 15% required revision surgery. Upton hand type was significantly associated with postoperative complication incidence, specifically including range-of-motion deficits, flexion contracture, web creep and revision surgery. More severe syndactylies may benefit from additional measures to reduce complications. Rectangular commissural flaps showed 1.9 times greater complication risk than interdigitating triangular flaps, including 11.2 times greater risk of web creep. Zigzag volar finger flaps showed 1.8 times greater complication risk than straight-line incisions, including 3.8 times greater risk of web creep. Our study showed that interdigitating triangular commissural flaps and straight-line volar finger incisions are preferable to rectangular commissural and zigzag finger flaps in most cases of Apert hand syndactyly to minimize complications.
LEVEL OF EVIDENCE
III.
Topics: Humans; Male; Female; Postoperative Complications; Surgical Flaps; Risk Factors; Infant; Plastic Surgery Procedures; Acrocephalosyndactylia; Child, Preschool; Reoperation; Retrospective Studies; Syndactyly; Child; Range of Motion, Articular
PubMed: 37987676
DOI: 10.1177/17531934231213516 -
Cureus Aug 2023Apert syndrome is a rare inherited syndrome characterised by craniosynostosis, midface hypoplasia, and syndactyly of the hands and feet. Syndactyly of the hands is...
Apert syndrome is a rare inherited syndrome characterised by craniosynostosis, midface hypoplasia, and syndactyly of the hands and feet. Syndactyly of the hands is categorised into three types with varying severity, requiring a diverse range of surgical techniques to produce good functional and aesthetic outcomes. The best age to initiate hand reconstruction is between three and 12 months. We present a case of a three-year-old boy with type III syndactyly who first presented at a volunteer outreach surgical campus in Pemba, Zanzibar. A three-stage bilateral hand reconstruction was initiated to sequentially create the first, fourth, and second web spaces. Postoperative healing was uneventful. He underwent a hand rehabilitation program and demonstrated good functional outcomes, being able to attend school, hold a pen, and write by seven years old. A literature review revealed that the best age to initiate hand reconstruction or the best surgical technique to use has yet to be agreed upon. It is agreed that the diverse symptoms of Apert syndrome make it difficult to manage, requiring multidisciplinary collaboration to provide physical and emotional benefits to patients and families.
PubMed: 37719615
DOI: 10.7759/cureus.43641 -
International Journal of Oral and... May 2024To determine the effect of midface surgery on soft tissue changes and their relationship to hard tissue changes in patients with syndromic craniosynostosis. A...
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.
PubMed: 38740540
DOI: 10.1016/j.ijom.2024.04.012 -
International Journal of Oral and... Apr 2024To determine the skeletal changes after midface surgery in patients with syndromic craniosynostosis who underwent Le Fort III (LFIII), monobloc (MB), or facial...
To determine the skeletal changes after midface surgery in patients with syndromic craniosynostosis who underwent Le Fort III (LFIII), monobloc (MB), or facial bipartition (FB). This was a retrospective study including 75 patients: 33 treated by LFIII, 29 by MB, and 13 by FB. Twenty-five had a diagnosis of Apert, 39 Crouzon, and 11 craniofrontonasal syndrome. A three-dimensional mesh was created from the preoperative scan and registered to the postoperative scan to visualise the advancement. LFIII at age 7-12 years effectuated a higher mean advancement in the maxillary (15.5 mm) and zygomatic (7.6 mm) regions when compared to ≥13 years (10.2 mm and 5.5 mm). After MB, mean advancement of the fronto-orbital region was higher at <7 years (16.4 mm), and similarly lower at ages 7-12 (13.8 mm) and ≥13 (12.5 mm). The mean preoperative inter-dacryon distance (34.4 ± 4.4 mm) was reduced by 8.7 ± 4.2 mm after FB without distraction (n = 10). More advancement was seen when midface surgery was performed at a younger age, due to more severe cases and a desire for overcorrection. The highest mean advancement was observed in the fronto-orbital region. Antero-inferior rotational movement was seen after all three techniques.
PubMed: 38594167
DOI: 10.1016/j.ijom.2024.03.010 -
Ophthalmology Mar 2024To determine the sensitivity, specificity, and cutoff of macular ganglion cell layer (GCL) volume consistent with optic atrophy in children with syndromic...
PURPOSE
To determine the sensitivity, specificity, and cutoff of macular ganglion cell layer (GCL) volume consistent with optic atrophy in children with syndromic craniosynostosis and to investigate factors independently associated with reduction in GCL volume.
DESIGN
Retrospective cross-sectional study.
PARTICIPANTS
Patients with syndromic craniosynostosis evaluated at Boston Children's Hospital (2010-2022) with reliable macular OCT scans.
METHODS
The latest ophthalmic examination that included OCT macula scans was identified. Age at examination, sex, ethnicity, best-corrected logarithm of the minimum angle of resolution (logMAR) visual acuity, cycloplegic refraction, and funduscopic optic nerve appearance were recorded in addition to history of primary or recurrent elevation in intracranial pressure (ICP), Chiari malformation, and obstructive sleep apnea (OSA). Spectral-domain OCT software quantified segmentation of macula retinal layers and was checked manually.
MAIN OUTCOME MEASURES
The primary outcome was determining sensitivity, specificity, and optimal cutoff of GCL volume consistent with optic atrophy. The secondary outcome was determining whether previously elevated ICP, OSA, Chiari malformation, craniosynostosis diagnosis, logMAR visual acuity, age, or sex were independently associated with lower GCL volume.
RESULTS
Median age at examination was 11.9 years (interquartile range, 8.5-14.8 years). Fifty-eight of 61 patients (112 eyes) had reliable macula scans, 74% were female, and syndromes represented were Apert (n = 14), Crouzon (n = 17), Muenke (n = 6), Pfeiffer (n = 6), and Saethre-Chotzen (n = 15). Optimal cutoff identifying optic atrophy was a GCL volume < 1.02 mm with a sensitivity of 83% and specificity of 77%. Univariate analysis demonstrated that significantly lower macular GCL volume was associated with optic atrophy on fundus examination (P < 0.001), Apert syndrome (P < 0.001), history of elevated ICP (P = 0.015), Chiari malformation (P = 0.001), OSA (P < 0.001), male sex (P = 0.027), and worse logMAR visual acuity (P < 0.001). Multivariable median regression analysis confirmed that only OSA (P = 0.005), optic atrophy on fundus examination (P = 0.003), and worse logMAR visual acuity (P = 0.042) were independently associated with lower GCL volume.
CONCLUSIONS
Surveillance for optic atrophy by GCL volume may be useful in a population where cognitive skills can limit acquisition of other key ophthalmic measures. It is noteworthy that OSA is also associated with lower GLC volume in this population.
FINANCIAL DISCLOSURE(S)
The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Topics: Child; Humans; Male; Female; Adolescent; Retinal Ganglion Cells; Cross-Sectional Studies; Retrospective Studies; Optic Atrophy; Intracranial Hypertension; Craniosynostoses; Tomography, Optical Coherence; Sleep Apnea, Obstructive
PubMed: 37742723
DOI: 10.1016/j.ophtha.2023.09.022 -
BioRxiv : the Preprint Server For... Apr 2024Calvarial nerves, along with vasculature, influence skull formation during development and following injury, but it remains unclear how calvarial nerves are spatially...
Calvarial nerves, along with vasculature, influence skull formation during development and following injury, but it remains unclear how calvarial nerves are spatially distributed during postnatal growth and aging. Studying the spatial distribution of nerves in the skull remains challenging due to a lack of methods to image and quantify 3D structures in intact bone. To visualize calvarial 3D neurovascular architecture, we imaged nerves and endothelial cells with lightsheet microscopy. We employed machine-learning-based segmentation to facilitate high-resolution characterization from post-natal day 0 (P0) to Week 80 (80wk). We found that TUBB3+ nerve density decreased with aging with the frontal bone demonstrating earlier onset age-related nerve loss than the parietal bone. In addition, nerves in the periosteum and dura mater exhibited similar yet distinct temporal patterns of nerve growth and loss. While no difference was observed in TUBB3+ nerves during skeletal maturation (P0 → 12wk), we did observe an increase in the volume of unmyelinated nerves in the dura mater. Regarding calvarial vasculature, larger CD31Emcn vessel density increased with aging, while CD31Emcn vessel density was reduced. For all nerve markers studied, calvarial nerves maintained a preferential spatial association with CD31Emcn vessels that decreased with aging. Additionally, we used a model of Apert syndrome that demonstrates early coronal suture fusion to explore the impact of suture-related disease on neurovascular architecture. We identified a mild dysregulation of dural nerves and minor shifts in vessel populations. Collectively, this 3D, spatiotemporal characterization of calvarial nerves throughout the lifespan and provides new insights into age-induced neurovascular architecture.
PubMed: 38617372
DOI: 10.1101/2024.03.28.587299 -
Genetics Aug 2023TWIST1 is a basic helix-loop-helix (bHLH) transcription factor in humans that functions in mesoderm differentiation. TWIST1 primarily regulates genes as a...
TWIST1 is a basic helix-loop-helix (bHLH) transcription factor in humans that functions in mesoderm differentiation. TWIST1 primarily regulates genes as a transcriptional repressor often through TWIST-Box domain-mediated protein-protein interactions. The TWIST-Box also can function as an activation domain requiring 3 conserved, equidistant amino acids (LXXXFXXXR). Autosomal dominant mutations in TWIST1, including 2 reported in these conserved amino acids (F187L and R191M), lead to craniofacial defects in Saethre-Chotzen syndrome (SCS). Caenorhabditis elegans has a single TWIST1 homolog, HLH-8, that functions in the differentiation of the muscles responsible for egg laying and defecation. Null alleles in hlh-8 lead to severely egg-laying defective and constipated animals due to defects in the corresponding muscles. TWIST1 and HLH-8 share sequence identity in their bHLH regions; however, the domain responsible for the transcriptional activity of HLH-8 is unknown. Sequence alignment suggests that HLH-8 has a TWIST-Box LXXXFXXXR motif; however, its function also is unknown. CRISPR/Cas9 genome editing was utilized to generate a domain deletion and several missense mutations, including those analogous to SCS patients, in the 3 conserved HLH-8 amino acids to investigate their functional role. The TWIST-Box alleles did not phenocopy hlh-8 null mutants. The strongest phenotype detected was a retentive (Ret) phenotype with late-stage embryos in the hermaphrodite uterus. Further, GFP reporters of HLH-8 downstream target genes (arg-1::gfp and egl-15::gfp) revealed tissue-specific, target-specific, and allele-specific defects. Overall, the TWIST-Box in HLH-8 is partially required for the protein's transcriptional activity, and the conserved amino acids contribute unequally to the domain's function.
Topics: Animals; Female; Humans; Acrocephalosyndactylia; Basic Helix-Loop-Helix Transcription Factors; Caenorhabditis elegans; Mutation; Transcription Factors; Twist-Related Protein 1
PubMed: 37067863
DOI: 10.1093/genetics/iyad066 -
Journal of Oral Biosciences Mar 2024The purpose of this study was to perform morphological and immunohistochemical (IHC) analysis of the submandibular glands (SMGs) in early development in Apert syndrome...
OBJECTIVES
The purpose of this study was to perform morphological and immunohistochemical (IHC) analysis of the submandibular glands (SMGs) in early development in Apert syndrome model mice (Ap mice).
METHODS
ACTB-Cre homozygous mice were mated with fibroblast growth factor receptor 2 (Fgfr2) mice; ACTB-Cre heterozygous mice (ACTB-Cre mice) at embryonic day (E) 13.5 served as the control group, and Fgfr2 mice (Ap mice) served as the experimental group. Hematoxylin and eosin (H&E) staining was performed on SMGs; Total SMG area and epithelial area were determined, and the epithelial occupancy ratio was calculated. Immunostaining was performed to assess the localization of FGF signaling-related proteins. Next, bromodeoxyuridine (BrdU)-positive cells were evaluated to assess cell proliferation. Finally, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining was performed to assess apoptosis in SMGs.
RESULTS
The epithelial occupancy ratio was significantly higher in SMGs of Ap mice compared with that in SMGs of controls. FGF7 and bone morphogenetic protein 4 (BMP4) exhibited different localizations in SMGs of Ap mice compared with SMGs of controls. Cell proliferation was higher in SMGs of Ap mice compared with that of controls; however, apoptosis did not different significantly between the two groups.
CONCLUSION
Our results suggest that enhanced FGF signaling conferred by missense mutations in FGFR2 promotes branching morphogenesis in SMGs of Ap mice.
Topics: Animals; Mice; Acrocephalosyndactylia; Morphogenesis; Mutation; Receptor, Fibroblast Growth Factor, Type 2; Submandibular Gland
PubMed: 38246420
DOI: 10.1016/j.job.2024.01.001 -
Journal of Cranio-maxillo-facial... Jan 2024Craniosynostosis, characterized by premature fusion of one or more cranial sutures, results in a distorted skull shape. Only three studies have assessed facial asymmetry...
Craniosynostosis, characterized by premature fusion of one or more cranial sutures, results in a distorted skull shape. Only three studies have assessed facial asymmetry manually in unicoronal synostosis patients. It is therefore important to understand how uni- and bicoronal synostosis affect facial asymmetry with a minimum risk of human bias. An automated algorithm was developed to quantify facial asymmetry from three-dimensional images, generating a mean facial asymmetry (MFA) value in millimeters to reflect the degree of asymmetry. The framework was applied to analyze postoperative 3D images of syndromic patients (N = 35) diagnosed with Muenke syndrome, Saethre-Chotzen syndrome, and TCF12-related craniosynostosis with respect to MFA values from a healthy control group (N = 89). Patients demonstrated substantially higher MFA values than controls: Muenke syndrome (unicoronal 1.74 ± 0.40 mm, bicoronal 0.77 ± 0.21 mm), Saethre-Chotzen syndrome (unicoronal 1.15 ± 0.20 mm, bicoronal 0.69 ± 0.16 mm), and TCF12-related craniosynostosis (unicoronal 1.40 ± 0.51 mm, bicoronal 0.66 ± 0.05 mm), compared with controls (0.49 ± 0.12 mm). Longitudinal analysis identified an increasing MFA trend in unicoronal synostosis patients. Our study revealed higher MFA in syndromic patients with uni- and bicoronal synostosis compared with controls, with the most pronounced MFA in Muenke syndrome patients with unilateral synostosis. Bicoronal synostosis patients demonstrated higher facial asymmetry than expected given the condition's symmetrical presentation.
Topics: Humans; Infant; Retrospective Studies; Facial Asymmetry; Craniosynostoses; Acrocephalosyndactylia
PubMed: 38135649
DOI: 10.1016/j.jcms.2023.11.006 -
Plastic and Reconstructive Surgery.... Jan 2024Apert syndrome classically presents with craniosynostosis at birth, most commonly of the bilateral coronal sutures, which may lead to cephalocranial disproportion and...
Apert syndrome classically presents with craniosynostosis at birth, most commonly of the bilateral coronal sutures, which may lead to cephalocranial disproportion and elevated intracranial pressure, the latter of which is associated with optic atrophy, visual loss, and developmental delays. A small number of patients with syndromic craniosynostosis demonstrate open sutures at birth; however, all previously reported patients of this subtype have been reported to develop premature suture fusion in the early postnatal period and/or require cranial vault expansion for increased intracranial pressure. Here, we report on a patient with Apert syndrome who did not have closed sutures at birth, and only began to demonstrate unilateral coronal suture fusion between ages 4 and 6 years, yet neither developed phenotypic signs of craniosynostosis nor evidence of intracranial hypertension. Moreover, despite demonstrating patency of the spheno-occipital synchondrosis, the patient developed progressive midface hypoplasia, requiring a subcranial Le Fort 3 advancement with external distraction at age 9. Now at skeletal maturity, this patient has a normal cranial shape and will likely never require cranial vault surgery for functional or aesthetic concerns. We are not aware of any prior reports of a patient with Apert syndrome who did not require intracranial surgery over long-term follow-up.
PubMed: 38264445
DOI: 10.1097/GOX.0000000000005558