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The Cleft Palate-craniofacial Journal :... Aug 2023Apert syndrome (AS) is a rare congenital craniofacial disorder that requires a multidisciplinary approach to treatment and multiple surgeries. Given that cleft palate...
OBJECTIVE
Apert syndrome (AS) is a rare congenital craniofacial disorder that requires a multidisciplinary approach to treatment and multiple surgeries. Given that cleft palate (CP) is presented in some of these cases, this poses an additional risk of aggravating obstructed airways after closure. The timing and outcome of CP repair in these patients remains disputed and requires additional attention.
DESIGN
This retrospective analysis included patients diagnosed with CP and AS, born between 1950 and 2020, and treated at our institution. Data were collected from medical records and evaluated using descriptive statistics.
SETTING
Data analyses were conducted at Sahlgrenska University Hospital in Gothenburg, Sweden.
PATIENTS/PARTICIPANTS
A registry of 83 patients with AS resulted in a cohort of 26 patients also presenting with CP.
MAIN OUTCOME MEASURES
Postoperative complications, requirement for intensive care, and reoperations following CP repair.
RESULTS
CP incidence among all registered patients was 31%. Patients undergoing CP repair at low age (mean: 22.5 months) tended to experience more frequent postoperative complications and requirements for intensive care. Among the evaluated cohort with medical records describing CP repair (= 14), 29% experienced postoperative complications, all of which involved aggravation of obstructed airways.
CONCLUSIONS
This study highlights the importance of airway assessment before and after CP repair in AS. The findings suggest that surgical outcomes might benefit from postponing CP repair, avoiding combined surgeries, and operating in two stages when indicated. However, additional and larger studies are required.
PubMed: 37563888
DOI: 10.1177/10556656231194445 -
Romanian Journal of Ophthalmology 2023Apert Syndrome (AS) is a rare form of acrocephalosyndactyly. The aim of the manuscript was to underline the challenging squint management in a case of Apert Syndrome. A...
Apert Syndrome (AS) is a rare form of acrocephalosyndactyly. The aim of the manuscript was to underline the challenging squint management in a case of Apert Syndrome. A 1.5-year-old male with craniosynostosis, diagnosed at birth, with history of incomplete closure of eyes, more so in the right eye, and squinting of left eye since birth, was brought to eye OPD by the mother. Presence of acrocephaly, prominent forehead with bony irregularity, chin down with left head tilt, fused cervical vertebrae, marked proptosis, cleft palate, dental anomaly and syndactyly confirmed the diagnosis of AS. Old serial photographs of the child were examined to look for progression of squint and proptosis. Squint evaluation revealed 70-75 PD exotropia with 10PD right hypertropia in primary gaze. The right hypertropia increased further in the left gaze, whereas a left hypertropia was noted in the right gaze. The patient underwent bilateral LR recession of 9 mm with full muscle width transposition (upshift) with Inferior Oblique recession of 4:1 mm in the right eye and 3:2 mm in the left eye. Post-operative follow-up after 2 months showed that V pattern collapsed with residual exotropia of 20 PD. Post-operative follow-up after 1 year showed improvement in head posture with pattern collapsed. However, recurrent exotropia was noted on evaluation, for which bilateral medial recti resection was done later. The management of squint in AS and other craniosynostosis poses a multitude of challenges for the ophthalmologists. Frequent follow-ups are needed in patients with AS for the timely management of its ocular manifestations and better visual rehabilitation.
PubMed: 37522017
DOI: 10.22336/rjo.2023.35 -
The Pan African Medical Journal 2023
Topics: Humans; Acrocephalosyndactylia; Syndactyly; Fingers; Toes
PubMed: 37521759
DOI: 10.11604/pamj.2023.45.24.38946 -
The Journal of Craniofacial Surgery Oct 2023Pfeiffer syndrome is characterized by craniosynostosis, mid-face hypoplasia, broad thumbs, and often multilevel airway obstruction. Airway management is often required,...
BACKGROUND
Pfeiffer syndrome is characterized by craniosynostosis, mid-face hypoplasia, broad thumbs, and often multilevel airway obstruction. Airway management is often required, including the use of positive airway ventilation, nasopharyngeal airway (NPA), or tracheostomy.
OBJECTIVE
The objective of this study was to assess the impact an airway adjunct can have on feeding difficulties in children with Pfeiffer syndrome.
METHODS
Retrospective review of patients diagnosed with Pfeiffer syndrome from January 1998 to January 2020 at one of England's 4 supraregional Craniofacial Units, Alder Hey Children's Hospital. Speech & Language Therapy case notes and medical notes were used to gather data, as well as the Oral Feeding Score component of the UK Craniofacial Outcome Score.
RESULTS
Eleven patients were included. Six patients had no airway adjunct (55%): 3 had tracheostomy (27%) and 2 patients had NPA (18%). All patients with airway adjuncts were percutaneous endoscopic gastrostomy/percutaneous endoscopic jejunostomy fed. Those who did not require an airway adjunct had an Oral Feeding Score of 4.60 (SD: 0.49). The children who went on to have an airway adjunct had a mean preintervention Oral Feeding Score of 2.4 (SD: 0.8). The mean feeding score (postairway adjunct) in the NPA group was 2.0, compared with the tracheostomy group scoring 3.0.
CONCLUSIONS
Children with Pfeiffer syndrome who require airway intervention have more significant feeding problems requiring feeding intervention. Although there were small numbers included in this study, there is a suggestion that airway adjuncts can contribute to feeding difficulties, particularly NPAs.
Topics: Humans; Child; Infant; Acrocephalosyndactylia; Airway Management; Airway Obstruction; Nasopharynx; Tracheostomy; Retrospective Studies
PubMed: 37477198
DOI: 10.1097/SCS.0000000000009541 -
Archives of Oral Biology Sep 2023Apert syndrome, an autosomal dominant congenital disorder characterized by craniosynostosis, is caused by a missense mutation (S252W or P253R) in fibroblast growth...
OBJECTIVE
Apert syndrome, an autosomal dominant congenital disorder characterized by craniosynostosis, is caused by a missense mutation (S252W or P253R) in fibroblast growth factor receptor 2 (FGFR2). Exosomes are naturally occurring carriers that deliver nucleic acids, including small interfering RNA (siRNA), to induce gene silencing. This study aimed to develop siRNA-loaded exosomes (Ex-siRNA) to silence the Fgfr2 gain-of-function mutation, thereby inhibiting the increased osteoblastic differentiation caused by the constitutive activation of FGFR2 signaling in calvarial osteoblastic cells isolated from Apert syndrome model mice.
DESIGN
Primary calvarial osteoblast-like cells were isolated from the embryonic calvarial sutures of the Apert syndrome model (Fgfr2) and littermate wild-type mice (Ap-Ob and Wt-Ob, respectively). Exosomes were extracted from the serum of wild-type mice, validated using biomarkers, and used to encapsulate siRNAs. After exosome-mediated siRNA transfection, cells were analyzed under a fluorescence microscope to validate the delivery of Ex-siRNA, followed by western blot and real-time reverse transcription polymerase chain reaction analyses.
RESULTS
After 24 h of Ex-siRNA delivery in both Ap-Ob and Wt-Ob, siRNA-loaded exosome delivery was validated. Moreover, p44/42 mitogen-activated protein kinase (MAPK) phosphorylation, runt-related transcription factor 2 (Runx2), and collagen type 1 alpha 1 (Col1a1) mRNA expression, and alkaline phosphatase (ALP) activity were significantly increased in Ap-Ob. The levels of phospho-p44/42 protein, Runx2, Col1a1, and ALP were significantly decreased after Ex-siRNA transfection but did not affect Wt-Ob.
CONCLUSIONS
These results indicate that exosome-mediated delivery of siRNA targeting Fgfr2 is a potential non-invasive treatment for aberrant FGF/FGFR signaling.
Topics: Mice; Animals; Acrocephalosyndactylia; Core Binding Factor Alpha 1 Subunit; RNA, Small Interfering; Exosomes; Cell Differentiation; Osteoblasts
PubMed: 37348363
DOI: 10.1016/j.archoralbio.2023.105753 -
Mammalian Genome : Official Journal of... Sep 2023The external ear develops from an organized convergence of ventrally migrating neural crest cells into the first and second branchial arches. Defects in external ear...
The external ear develops from an organized convergence of ventrally migrating neural crest cells into the first and second branchial arches. Defects in external ear position are often symptomatic of complex syndromes such as Apert, Treacher-Collins, and Crouzon Syndrome. The low set ears (Lse) spontaneous mouse mutant is characterized by the dominant inheritance of a ventrally shifted external ear position and an abnormal external auditory meatus (EAM). We identified the causative mutation as a 148 Kb tandem duplication on Chromosome 7, which includes the entire coding sequences of Fgf3 and Fgf4. Duplications of FGF3 and FGF4 occur in 11q duplication syndrome in humans and are associated with craniofacial anomalies, among other features. Intercrosses of Lse-affected mice revealed perinatal lethality in homozygotes, and Lse/Lse embryos display additional phenotypes including polydactyly, abnormal eye morphology, and cleft secondary palate. The duplication results in increased Fgf3 and Fgf4 expression in the branchial arches and additional discrete domains in the developing embryo. This ectopic overexpression resulted in functional FGF signaling, demonstrated by increased Spry2 and Etv5 expression in overlapping domains of the developing arches. Finally, a genetic interaction between Fgf3/4 overexpression and Twist1, a regulator of skull suture development, resulted in perinatal lethality, cleft palate, and polydactyly in compound heterozygotes. These data indicate a role for Fgf3 and Fgf4 in external ear and palate development and provide a novel mouse model for further interrogation of the biological consequences of human FGF3/4 duplication.
Topics: Animals; Mice; Humans; Fibroblast Growth Factors; Mutation; Disease Models, Animal; Polydactyly; Fibroblast Growth Factor 3
PubMed: 37341808
DOI: 10.1007/s00335-023-09999-8 -
Neurology India 2023Various surgical techniques for cranial reconstruction of patients with bicoronal synostosis have been suggested. The outcome is, however, still often suboptimal.
BACKGROUND
Various surgical techniques for cranial reconstruction of patients with bicoronal synostosis have been suggested. The outcome is, however, still often suboptimal.
METHODS
In a 5-month-old child with apert syndrome, following a craniotomy incision, lambdoid suturotomy was done bilaterally. Two springs were implanted bilaterally over the lambdoid sutures. Cephalic index was obtained from three-dimensional computed tomography scans, and photographs were analyzed for aesthetic evaluation.
RESULT
The preoperative calvarial shape was hyperbrachycephalic. The CI improved from 92 to 83 units. Duration of surgery was 1 h 45 min, blood loss was 30 mL, and total hospital stay was 3 days. No major complications were observed. Spring removal was done at 6 months postoperatively and frontoorbital advancement performed.
CONCLUSION
Spring-assisted cranioplasty for bicoronal synostosis is a safe and elegant technique, is less invasive than many other cranioplasties, and results in marked improvement in the calvarial shape.
Topics: Child; Humans; Infant; Treatment Outcome; Skull; Craniosynostoses; Cranial Sutures; Craniotomy; India
PubMed: 37322751
DOI: 10.4103/0028-3886.378708 -
Advances and Technical Standards in... 2023Apert syndrome is characterized by a wide spectrum of craniofacial clinical features that have been successfully addressed via a variety of midface advancement... (Review)
Review
Apert syndrome is characterized by a wide spectrum of craniofacial clinical features that have been successfully addressed via a variety of midface advancement techniques. Although surgeons have individual preferences as to which specific procedures should be performed to best treat Apert patients, craniofacial plastic surgeons, working in tandem with pediatric neurosurgeons, can identify and evaluate functional limitations and facial morphologic disproportions, and establish appropriate criteria for effective midface advancement technique indication and selection. The purpose of this review article is to present and discuss our rationale for midface advancement technique selection based upon the most common craniofacial characteristics presented by Apert syndrome patients. The present article also provides a grading system that stratifies as major, moderate, and mild, the effect of each midface advancement technique on the different types of Apert syndrome facial features. Surgeons should take into consideration the maximum effect and benefit of each craniofacial osteotomy and how these procedures will alter the craniofacial skeleton. By understanding the long-term effect of each osteotomy on the most common craniofacial characteristics of Apert syndrome patients, craniofacial plastic surgeons and neurosurgeons will be able to customize the surgical procedures they perform in order to achieve the best possible outcomes.
Topics: Humans; Child; Acrocephalosyndactylia; Retrospective Studies; Osteotomy, Le Fort; Face
PubMed: 37318579
DOI: 10.1007/978-3-031-28202-7_13 -
The Journal of Craniofacial Surgery Oct 2023Jacobs syndrome is a rare trisomy (47, XYY) found in ~1 in 1000 male children associated with infertility, autism spectrum disorders, macrocephaly, hypertelorism, tall...
Jacobs syndrome is a rare trisomy (47, XYY) found in ~1 in 1000 male children associated with infertility, autism spectrum disorders, macrocephaly, hypertelorism, tall stature, and macroorchidism. Diagnosis is often delayed due to relatively subtle phenotypic changes. Craniosynostosis, a fusion of the cranial sutures, has been described in ~1 in 2000 live births, of which 25% are related to a diagnosed syndrome with the most common being Apert and Crouzon. Craniosynostosis does not have a known association with Jacobs syndrome and no prior cases have been reported. This case report seeks to describe the presentation and treatment of a patient with Jacobs syndrome and metopic craniosynostosis.
Topics: Child; Humans; Male; Craniosynostoses; Cranial Sutures; Arthropathy, Neurogenic
PubMed: 37259204
DOI: 10.1097/SCS.0000000000009458