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Taiwanese Journal of Obstetrics &... May 2024We present perinatal imaging findings of a fetus with Pfeiffer syndrome and a heterozygous c.1019A>G, p.Tyr340Cys (Y340C) mutation in FGFR2 presenting a cloverleaf...
Perinatal imaging findings of a fetus with Pfeiffer syndrome and a heterozygous c.1019A>G, p.Tyr340Cys (Y340C) mutation in FGFR2 presenting a cloverleaf skull, craniosynostosis and short limbs on prenatal ultrasound mimicking thanatophoric dysplasia type II.
OBJECTIVE
We present perinatal imaging findings of a fetus with Pfeiffer syndrome and a heterozygous c.1019A>G, p.Tyr340Cys (Y340C) mutation in FGFR2 presenting a cloverleaf skull, craniosynostosis and short limbs on prenatal ultrasound mimicking thanatophoric dysplasia type II (TD2).
CASE REPORT
A 37-year-old, gravida 2, para 1, woman underwent amniocentesis at 17 weeks of gestation because of advanced maternal age. Amniocentesis revealed a karyotype of 46,XY. However, craniofacial anomaly was found on prenatal ultrasound at 21 weeks of gestation, which showed a cloverleaf skull with severe craniosynostosis and relatively short straight long bones. Fetal magnetic resonance imaging (MRI) analysis at 22 weeks of gestation showed a cloverleaf skull, proptosis and relatively shallowing of the sylvian fissures. Prenatal ultrasound at 24 weeks of gestation showed a fetus with a cloverleaf skull with a biparietal diameter (BPD) of 6.16 cm (equivalent to 24 weeks), an abdominal circumference (AC) of 18.89 cm (equivalent to 24 weeks) and a femur length (FL) of 3.65 cm (equivalent to 21 weeks). A tentative diagnosis of TD2 was made. The pregnancy was subsequently terminated, and a 928-g malformed fetus was delivered with severe craniosynostosis, proptosis, midface retrusion, a cloverleaf skull, broad thumbs and broad big toes. The broad thumbs were medially deviated. Whole body X-ray showed a cloverleaf skull and straight long bones. However, molecular analysis of FGFR3 on the fetus revealed no mutation in the target regions. Subsequent whole exome sequencing (WES) on the DNA extracted from umbilical cord revealed a heterozygous c.1019A>G, p.Tyr340Cys (Y340C) mutation in the FGFR2 gene.
CONCLUSION
Fetuses with a Y340C mutation in FGFR2 may present a cloverleaf skull on prenatal ultrasound, and WES is useful for a rapid differential diagnosis of Pfeiffer syndrome from TD2 under such a circumstance.
Topics: Humans; Female; Acrocephalosyndactylia; Pregnancy; Ultrasonography, Prenatal; Adult; Receptor, Fibroblast Growth Factor, Type 2; Craniosynostoses; Thanatophoric Dysplasia; Mutation; Diagnosis, Differential; Magnetic Resonance Imaging; Heterozygote; Infant, Newborn; Skull
PubMed: 38802203
DOI: 10.1016/j.tjog.2024.03.005 -
Journal of Orthopaedic Science :... May 2024Webplasty can be conducted for complex syndactyly caused by Apert syndrome (also referred to as Apert hand) by extending the soft tissue in the lateral direction using...
BACKGROUND
Webplasty can be conducted for complex syndactyly caused by Apert syndrome (also referred to as Apert hand) by extending the soft tissue in the lateral direction using an external fixator. This study aimed to verify the usefulness of webplasty without skin grafting.
METHODS
Webplasty with lateral extension was conducted at a single institution from 2015 to 2023. The patients were four children with Apert hand aged 1-3 years. A custom-made small external fixator was used for all of the soft tissue extension.
RESULTS
Webplasty without skin grafting was completed by the time all five patients were 5-6 years of age.
CONCLUSION
Webplasty without skin grafting was possible with lateral extension of the soft tissue using a simple external fixator.
PubMed: 38772762
DOI: 10.1016/j.jos.2024.04.007 -
Iranian Journal of Allergy, Asthma, and... Feb 2024Sanjad Sakati Syndrome (SSS) is categorized as a neuroendocrine-related disease due to disorders of the nervous and hormonal systems. Since hormonal changes in these...
Sanjad Sakati Syndrome (SSS) is categorized as a neuroendocrine-related disease due to disorders of the nervous and hormonal systems. Since hormonal changes in these patients may affect the nature and function of the immune system. Thus, in this study, cell count and phagocytotic function of neutrophils were evaluated which may be influenced by changes in the hormonal rate and growth factors. In this study, the neutrophil count value and the oxidative burst were evaluated in six patients diagnosed with SSS and six healthy individuals. There was a significant reduction in the neutrophil count observed in SSS patients compared to healthy controls (37.41±7.93 percent vs. 66.5±6.8 percent). However, there was no significant difference in neutrophil oxidative index between patients with SSS and control subjects (172.33±55.08 vs. 217.00±77.38). We concluded that in patients with SSS, the phagocytic activity of neutrophils was not affected by hormonal changes, while the number of neutrophils and neutrophil-to-lymphocyte ratio (NLR) index were decreased.
Topics: Humans; Neutrophils; Respiratory Burst; Intellectual Disability; Leukocyte Count; Lymphocyte Count; Abnormalities, Multiple; Growth Disorders; Acrocephalosyndactylia; Osteochondrodysplasias; Hypoparathyroidism; Seizures
PubMed: 38485906
DOI: 10.18502/ijaai.v23i1.14959 -
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 AAPOS : the Official... Feb 2024To better characterize the correlation of bony orbital dysmorphology with strabismus in craniosynostosis.
PURPOSE
To better characterize the correlation of bony orbital dysmorphology with strabismus in craniosynostosis.
METHODS
The medical records of patients with craniosynostosis with and without strabismus seen at Rady Children's Hospital (San Diego, CA) from March 2020 to January 2022 were reviewed retrospectively in this masked, case-control study. Computed tomography scans of the orbits were analyzed to obtain dimensions of the orbital entrance and orbital cone. Primary outcome was correlation of strabismus with orbital measurements.
RESULTS
A total of 30 orbits from 15 patients with strabismus and 15 controls were included. Craniofacial disorders included in the study were nonsyndromic craniosynostosis (63%), Crouzon syndrome (13%), Apert syndrome (13%), and Pfeiffer syndrome (10%). Orbital index (height:width ratio) (P = 0.01) and medial orbital wall angle (P = 0.04) were found to differ significantly between the strabismus and control groups.
CONCLUSIONS
In our small cohort, bony orbital dimensions, including the ratio of orbital height to width and bowing of the medial orbital wall, were associated with strabismus in craniosynostosis.
Topics: Child; Humans; Case-Control Studies; Retrospective Studies; Craniosynostoses; Acrocephalosyndactylia; Strabismus; Orbit
PubMed: 38219920
DOI: 10.1016/j.jaapos.2023.10.006 -
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 -
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 -
The Journal of Craniofacial Surgery Oct 2023The objective of this study is to report the outcomes of a modified comprehensive Apert syndrome surgical protocol in which fat injection was performed during early...
BACKGROUND
The objective of this study is to report the outcomes of a modified comprehensive Apert syndrome surgical protocol in which fat injection was performed during early infancy concurrent with postposterior vault distraction osteogenesis (PVDO) distractor removal.
METHODS
A retrospective study was performed on 40 consecutive young patients with Apert syndrome who underwent PVDO and subsequent distractor removal between 2012 and 2022. Of these 40 patients, 12 patients underwent facial fat injection concurrent with distractor removal to treat residual supraorbital bar recession as part of a modified comprehensive Apert syndrome surgical protocol. Preoperative and postoperative severity of recession and irregularity was graded from 1 to 3, with 1 being less severe and 3 being the most severe. Recession severity was correlated with the number and type of suture fusion. The complication rate was stratified via a Clavien-Dindo scale.
RESULTS
The average patient age was 14.3±5 months, with 5 males (41.6%) and 7 females (48.3%). The average hospital stay was 1.08 days. The average volume of free fat graft injection was 8.29±5 mL. According to the Likert scale, forehead morphology improved in 91.67% of the patients. Complete resolution of supraorbital bar recession was achieved in seven patients (58.33%), all of whom presenting a single suture synostosis. One patient with a cloverleaf skull presented a type IIIB complication.
CONCLUSIONS
Facial fat grafting markedly reduces forehead asymmetry and improves forehead contour in Apert syndrome patients following PVDO. Total resolution of forehead recession directly correlated with a single suture fusion.
Topics: Female; Humans; Infant; Male; Acrocephalosyndactylia; Craniosynostoses; Face; Forehead; Osteogenesis, Distraction; Retrospective Studies; Subcutaneous Fat
PubMed: 37594030
DOI: 10.1097/SCS.0000000000009610 -
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