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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 Pan African Medical Journal 2023
Topics: Humans; Acrocephalosyndactylia; Syndactyly; Fingers; Toes
PubMed: 37521759
DOI: 10.11604/pamj.2023.45.24.38946 -
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 -
Medicine Oct 2022Fetal skeletal anomalies are one of the most common and potentially pathogenic developmental abnormalities detected by ultrasound screening. Any suspected fetal skeletal...
RATIONALE
Fetal skeletal anomalies are one of the most common and potentially pathogenic developmental abnormalities detected by ultrasound screening. Any suspected fetal skeletal dysplasias often require further comprehensive evaluations.
PATIENT CONCERNS
Here 4 families with adverse fetal skeletal system histories were enrolled, including their histories of gestation, childbirth, familial skeletal abnormalities, and pregnancy outcomes. The corresponding diagnosis were done by whole exome sequencing (WES) combined with dynamic examination.
DIAGNOSIS
All of the families were definitively diagnosed through cytogenetics, molecular genetics, ultrasound, combined with multidisciplinary evaluation. Both of the fetuses in case 1 and case 2 were diagnosed with thanatophoric dysplasia type I, while the neonate in case 3 was diagnosed with Apert syndrome and a 3-years-old proband daughter with Crouzon syndrome in case 4.
INTERVENTIONS
We conducted karyotyping, copy number variation sequencing (CNV-seq), combined with WES to evaluate genetic conditions of abnormal fetus, neonate or proband patient. WES was preferred to obtain a relatively definitive diagnosis.
OUTCOMES
In cases 1 and 2, the families decided to choose termination of pregnancy due to fatal dysplasias. The couple in case 3, delivered a female baby diagnosed with Apert syndrome. Fortunately, in case 4, the family, which had a 3-years-old baby with Crouzon syndrome, gave birth to a healthy baby through prenatal diagnosis.
LESSONS SUBSECTIONS
Invasive prenatal diagnosis and dynamic assessments for the management of fetal skeletal dysplasias could contribute to revealing possible causes of fetal skeletal abnormalities and help clinicians conduct further genetic counseling in clinical practice.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Child, Preschool; Exome Sequencing; DNA Copy Number Variations; Acrocephalosyndactylia; Fetus; Prenatal Diagnosis; Osteochondrodysplasias; Musculoskeletal Abnormalities; Craniofacial Dysostosis; Ultrasonography, Prenatal
PubMed: 36316869
DOI: 10.1097/MD.0000000000031321 -
Genes Oct 2022Objective: To report the clinical and radiographic findings and molecular etiology of the first monozygotic twins affected with Pfeiffer syndrome. Methods: Clinical and...
Objective: To report the clinical and radiographic findings and molecular etiology of the first monozygotic twins affected with Pfeiffer syndrome. Methods: Clinical and radiographic examination and whole exome sequencing were performed on two monozygotic twins with Pfeiffer syndrome. Results: An acceptor splice site mutation in FGFR2 (c.940-2A>G) was detected in both twins. The father and both twins shared the same haplotype, indicating that the mutant allele was from their father’s chromosome who suffered severe upper airway obstruction and subsequent obstructive sleep apnea. Hypertrophy of nasal turbinates appears to be a newly recognized finding of Pfeiffer syndrome. Increased intracranial pressure in both twins were corrected early by fronto-orbital advancement with skull expansion and open osteotomy, in order to prevent the more severe consequences of increased intracranial pressure, including hydrocephalus, the bulging of the anterior fontanelle, and the diastasis of suture. Conclusions: Both twins carried a FGFR2 mutation and were discordant for lambdoid synostosis. Midface hypoplasia, narrow nasal cavities, and hypertrophic nasal turbinates resulted in severe upper airway obstruction and subsequent obstructive sleep apnea in both twins. Hypertrophy of the nasal turbinates appears to be a newly recognized finding of Pfeiffer syndrome. Fronto-orbital advancement with skull expansion and open osteotomy was performed to treat increased intracranial pressure in both twins. This is the first report of monozygotic twins with Pfeiffer syndrome.
Topics: Humans; Acrocephalosyndactylia; Twins, Monozygotic; Sleep Apnea, Obstructive; Airway Obstruction; Hypertrophy
PubMed: 36292735
DOI: 10.3390/genes13101850 -
The Journal of Neuroscience : the... Sep 2022multiple epidermal growth factor-like domains 8 (dMegf8) is a homolog of human encodes a multidomain transmembrane protein which is highly conserved across species....
multiple epidermal growth factor-like domains 8 (dMegf8) is a homolog of human encodes a multidomain transmembrane protein which is highly conserved across species. In humans, mutations cause a rare genetic disorder called Carpenter syndrome, which is frequently associated with abnormal left-right patterning, cardiac defects, and learning disabilities. is also associated with psychiatric disorders. Despite its clinical relevance, remains poorly characterized; and although it is highly conserved, studies on animal models of Megf8 are also very limited. The presence of intellectual disabilities in Carpenter syndrome patients and association of with psychiatric disorders indicate that mutations in cause underlying defects in synaptic structure and functions. In this study, we investigated the role of dMegf8 in glutamatergic synapses of the larval neuromuscular junctions (NMJ) in both males and females. We show that dMegf8 localizes to NMJ synapses and is required for proper synaptic growth. mutant larvae and adults show severe motor coordination deficits. At the NMJ, mutants show altered localization of presynaptic and postsynaptic proteins, defects in synaptic ultrastructure, and neurotransmission. Interestingly, mutants have reduced levels of the Type II BMP receptor Wishful thinking (). displays genetic interactions with () and , and in association with Dnrx and Wit plays an essential role in synapse organization. Our studies provide insights into human MEGF8 functions and potentially into mechanisms that may underlie intellectual disabilities observed in Carpenter syndrome as well as MEGF8-related synaptic structural and/or functional deficits in psychiatric disorders. Carpenter syndrome, known for over a century now, is a genetic disorder linked to mutations in () gene and associated with intellectual disabilities among other symptoms. is also associated with psychiatric disorders. Despite the high genetic conservation and clinical relevance, the functions of remain largely uncharacterized. Patients with intellectual disabilities and psychiatric diseases often have an underlying defect in synaptic structure and function. This work defines the role of the fly homolog of human , , in glutamatergic synapse growth, organization, and function and provide insights into potential functions of in human central synapses and synaptic mechanisms that may underlie psychiatric disorders and intellectual disabilities seen in Carpenter syndrome.
Topics: Acrocephalosyndactylia; Animals; Drosophila; Drosophila Proteins; EGF Family of Proteins; Female; Humans; Intellectual Disability; Male; Membrane Proteins; Mutation; Receptors, Cell Surface; Synapses
PubMed: 35944997
DOI: 10.1523/JNEUROSCI.0442-22.2022