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BMC Ophthalmology Feb 2024To report a case of a 4-year-old patient with Goldenhar syndrome. (Review)
Review
BACKGROUND
To report a case of a 4-year-old patient with Goldenhar syndrome.
CASE PRESENTATION
The author presents a rare case report involving a 4-year-old boy with multiple malformations. A comprehensive examination showed that the patient primarily had a limbal dermoid. He also has bilateral microtia and ear canal deformities. The skull CT scan and spine X-ray showed Maxillofacial Abnormalities and scoliosis. Whole Exome Sequencing revealed potential gene variations related to microtia. Although certain circumstances prevented us from initiating follow-up treatment for the patient, we have provided a detailed account of the diagnostic methodologies used for this condition.
CONCLUSIONS
Goldenhar syndrome is a congenital condition, predominantly presenting as sporadic cases. Its diagnosis and management typically necessitate the involvement of multiple disciplines, including otolaryngology and craniofacial surgery. The syndrome encompasses a variety of craniofacial features, which can facilitate early diagnosis and guide subsequent therapeutic interventions.
Topics: Male; Humans; Child, Preschool; Goldenhar Syndrome; Congenital Microtia; Abnormalities, Multiple; Tomography, X-Ray Computed; Eye Neoplasms
PubMed: 38388885
DOI: 10.1186/s12886-024-03317-9 -
Journal of Cranio-maxillo-facial... May 2024The aim of our study was to evaluate the effectiveness of intraoperative tranexamic acid (TXA) administration in decreasing transfusion needs in patients undergoing...
The aim of our study was to evaluate the effectiveness of intraoperative tranexamic acid (TXA) administration in decreasing transfusion needs in patients undergoing modified pi-plasty. A retrospective study was performed using a population of 59 patients who underwent modified pi-plasty, wherein patients who received TXA during surgery (study group, n = 26) were compared with patients who did not receive TXA (control group, n = 33). The primary study endpoints were intraoperative red blood cell substitution (%), postoperative red blood cell substitution (%), total red blood cell substitution (%), and hematocrit variation. Perioperative administration of TXA significantly decreased the total red blood cell substitution (62.90% vs 86.70%; p = 0.002) and resulted in a higher postoperative hematocrit (29.47% vs 27.53%; p = 0.060). In conclusion, perioperative administration of TXA significantly decreased blood transfusion requirements in patients with sagittal craniosynostosis undergoing modified pi-plasty.
Topics: Humans; Tranexamic Acid; Craniosynostoses; Retrospective Studies; Male; Female; Blood Transfusion; Infant; Antifibrinolytic Agents; Plastic Surgery Procedures; Blood Loss, Surgical; Hematocrit
PubMed: 38378370
DOI: 10.1016/j.jcms.2024.02.024 -
Journal of Orthopaedic Surgery and... Feb 2024The pathogenesis of coronal suture craniosynostosis is often attributed to the dysregulated cellular dynamics, particularly the excessive proliferation and abnormal...
Periostin/Bone Morphogenetic Protein 1 axis axis regulates proliferation and osteogenic differentiation of sutured mesenchymal stem cells and affects coronal suture closure in the TWIST1 mouse model of craniosynostosis.
BACKGROUND AND OBJECTIVE
The pathogenesis of coronal suture craniosynostosis is often attributed to the dysregulated cellular dynamics, particularly the excessive proliferation and abnormal osteogenic differentiation of suture cells. Despite its clinical significance, the molecular mechanims of this condition remain inadequately understood. This study is dedicated to exploring the influence of the Periostin/Bone Morphogenetic Protein 1 (BMP1) axis on the growth and osteogenic maturation of Suture Mesenchymal Stem Cells (SMSCs), which are pivotal in suture homeostasis.
METHODS
Neonatal TWIST Basic Helix-Loop-Helix Transcription Factor 1 heterozygous (TWIST1) mice, aged one day, were subjected to adenoviral vector-mediated Periostin upregulation. To modulate Periostin/BMP1 levels in SMSCs, we employed siRNA and pcDNA 3.1 vectors. Histological and molecular characterizations, including hematoxylin and eosin staining, Western blot, and immunohistochemistry were employed to study suture closure phenotypes and protein expression patterns. Cellular assays, encompassing colony formation, 5-ethynyl-2'deoxyuridine, and wound healing tests were conducted to analyze SMSC proliferation and migration. Osteogenic differentiation was quantified using Alkaline Phosphatase (ALP) and Alizarin Red S (ARS) staining, while protein markers of proliferation and differentiation were evaluated by Western blotting. The direct interaction between Periostin and BMP1 was validated through co-immunoprecipitation assays.
RESULTS
In the TWIST1 model, an upregulation of Periostin coupled with a downregulation of BMP1 was observed. Augmenting Periostin expression mitigated craniosynostosis. In vitro, overexpression of Periostin or BMP1 knockdown suppressed SMSC proliferation, migration, and osteogenic differentiation. Periostin knockdown manifested an inverse biological impact. Notably, the suppressive influence of Periostin overexpression on SMSCs was effectively counteracted by upregulating BMP1. There was a direct interaction between Periostin and BMP1.
CONCLUSION
These findings underscore the significance of the Periostin/BMP1 axis in regulating craniosynostosis and SMSC functions, providing new insights into the molecular mechanisms of craniosynostosis and potential targets for therapeutic intervention.
Topics: Mice; Animals; Osteogenesis; Periostin; Bone Morphogenetic Protein 1; Craniosynostoses; Cell Differentiation; Mesenchymal Stem Cells; Disease Models, Animal; Cell Proliferation; Cells, Cultured
PubMed: 38369459
DOI: 10.1186/s13018-024-04604-3 -
Journal of Veterinary Internal Medicine 2024Brachycephalic dogs display sleep-disordered breathing (SDB). The risk factors for SDB remain unknown.
BACKGROUND
Brachycephalic dogs display sleep-disordered breathing (SDB). The risk factors for SDB remain unknown.
OBJECTIVES
To identify risk factors for SDB. We hypothesized that brachycephaly, increasing severity of brachycephalic obstructive airway syndrome (BOAS), excess weight, and aging predispose to SDB.
ANIMALS
Sixty-three privately owned pet dogs were prospectively recruited: 28 brachycephalic and 35 normocephalic (mesaticephalic or dolicocephalic) dogs.
METHODS
Prospective observational cross-sectional study with convenience sampling. Recording with the neckband was done over 1 night at each dog's home. The primary outcome measure was the obstructive respiratory event index (OREI). Body condition score (BCS) was assessed, and BOAS severity was graded for brachycephalic dogs.
RESULTS
Brachycephaly was a significant risk factor for high OREI value (ratio of the geometric means 5.6, 95% confidence interval [CI] 3.2-9.9; P < .001) but aging was not (1.1, 95% CI 1.0-1.2; P = .2). Excess weight, defined as a BCS of over 5/9, (3.5, 95% CI 1.8-6.7; P < .001) was a significant risk factor. In brachycephalic dogs, BOAS-positive class (moderate or severe BOAS signs) was a significant risk factor (2.5, 95% CI 1.1-5.6; P = .03).
CONCLUSIONS AND CLINICAL IMPORTANCE
Brachycephaly decreases welfare in a multitude of ways, including disrupting sleep. Brachycephaly, increasing severity of BOAS and excess weight are risk factors for obstructive SDB.
Topics: Dogs; Animals; Cross-Sectional Studies; Dog Diseases; Risk Factors; Airway Obstruction; Sleep Apnea Syndromes; Craniosynostoses
PubMed: 38358051
DOI: 10.1111/jvim.17019 -
The Journal of Clinical Investigation Feb 2024The rediscovery of meningeal lymphatic vessels (MLVs) has sparked research interest in their function in numerous neurological pathologies. Craniosynostosis (CS) is...
The rediscovery of meningeal lymphatic vessels (MLVs) has sparked research interest in their function in numerous neurological pathologies. Craniosynostosis (CS) is caused by a premature fusion of cranial sutures during development. In this issue of the JCI, Matrongolo and colleagues show that Twist1-haploinsufficient mice that develop CS exhibit raised intracranial pressure, diminished cerebrospinal fluid (CSF) outflow, and impaired paravascular CSF-brain flow; all features that were associated with MLV defects and exacerbated pathology in mouse models of Alzheimer's disease. Activation of the mechanosensor Piezo1 with Yoda1 restored MLV function and CSF perfusion in CS models and in aged mice, opening an avenue for further development of therapeutics.
Topics: Mice; Animals; Brain; Lymphatic Vessels; Craniosynostoses; Alzheimer Disease; Disease Models, Animal; Ion Channels
PubMed: 38357924
DOI: 10.1172/JCI176858 -
European Journal of Medical Genetics Apr 2024Diaphanospondylodysostosis is a rare genetic skeletal disorder caused by biallelic variants in the BMPER gene. The term, diaphanospondylodysostosis, includes...
Diaphanospondylodysostosis is a rare genetic skeletal disorder caused by biallelic variants in the BMPER gene. The term, diaphanospondylodysostosis, includes ischiospinal dysotosis, which was previously known as a distinct entity with milder clinical features. The clinical phenotype of diaphanospondylodysostosis is quite variable with mortality in early postnatal life in some patients. Main clinical and radiographic features are narrow thorax, vertebral segmentation defects, rib anomalies, ossification defects of vertebrae, ischium and sacrum, and renal cysts. In this study, we report on a 14-year-old girl patient with diaphanospondylodysostosis harbouring a novel BMPER mutation. The patient presented with severe scoliosis and severely hypoplastic/aplastic distal phalanges of the fingers and toes, findings yet hitherto not described in this syndrome.
Topics: Female; Humans; Adolescent; Scoliosis; Spine; Dysostoses; Ribs; Osteochondrodysplasias; Carrier Proteins; Craniofacial Abnormalities
PubMed: 38355094
DOI: 10.1016/j.ejmg.2024.104924 -
Environment International Feb 2024Nickel, a common environmental hazard, is a risk factor for craniosynostosis. However, the underlying biological mechanism remains unclear. Here, we found that...
Nickel, a common environmental hazard, is a risk factor for craniosynostosis. However, the underlying biological mechanism remains unclear. Here, we found that early-life nickel exposure induced craniosynostosis in mice. In vitro, nickel promoted the osteogenic differentiation of human mesenchymal stem cells (hMSCs), and its osteogenic ability in vivo was confirmed by an ectopic osteogenesis model. Further mRNA sequencing showed that ERK1/2 signaling and FGFR2 were aberrantly activated. FGFR2 was identified as a key regulator of ERK1/2 signaling. By promoter methylation prediction and methylation-specific PCR (MSP) assays, we found that nickel induced hypomethylation in the promoter of FGFR2, which increased its binding affinity to the transcription factor Sp1. During pregnancy and postnatal stages, AZD4547 rescued nickel-induced craniosynostosis by inhibiting FGFR2 and ERK1/2. Compared with normal individuals, nickel levels were increased in the serum of individuals with craniosynostosis. Further logistic and RCS analyses showed that nickel was an independent risk factor for craniosynostosis with a nonlinear correlation. Mediated analysis showed that FGFR2 mediated 30.13% of the association between nickel and craniosynostosis risk. Collectively, we demonstrate that early-life nickel exposure triggers the hypomethylation of FGFR2 and its binding to Sp1, thereby promoting the osteogenic differentiation of hMSCs by ERK1/2 signaling, leading to craniosynostosis.
Topics: Female; Pregnancy; Mice; Humans; Animals; MAP Kinase Signaling System; Nickel; Osteogenesis; Craniosynostoses; Signal Transduction; Receptor, Fibroblast Growth Factor, Type 2
PubMed: 38340406
DOI: 10.1016/j.envint.2024.108477 -
American Journal of Veterinary Research Apr 2024To define reference intervals (RIs) for arterial blood gas (aBG) measurements in healthy, nonsedated, dolichocephalic, and mesocephalic (nonbrachycephalic) dogs at...
OBJECTIVE
To define reference intervals (RIs) for arterial blood gas (aBG) measurements in healthy, nonsedated, dolichocephalic, and mesocephalic (nonbrachycephalic) dogs at approximately 1,535 m above sea level and compare these findings with healthy, nonsedated, brachycephalic dogs living at the same altitude.
ANIMALS
120 adult nonbrachycephalic dogs and 20 adult brachycephalic dogs.
METHODS
Cases were prospectively enrolled from October 2021 to June 2022. Dogs were enrolled from the community or after presentation for wellness examinations or minor injuries including lacerations, nail injuries, and lameness. Physical examinations and systolic blood pressure (sBP) measurements were obtained before blood sample collection. Arterial blood was collected from the dorsal pedal artery or femoral artery. After data collection, brachycephalic dogs underwent pre- and postexercise tolerance assessments.
RESULTS
The mean and RI values for arterial pH (7.442; 7.375 to 7.515), partial pressure of oxygen in arterial blood (Pao2; 78.3; 59.2 to 92.7 mm Hg), partial pressure of carbon dioxide in arterial blood (Paco2; 28.0; 21.5 to 34.4 mm Hg), saturation of arterial oxygen (Sao2; 98.4; 84.3% to 101.4%), HCO3 (18.9; 14.9 to 22.4 mmol/L), concentration of total hemoglobin (ctHb; 17.5; 13.4 to 21.1 g/dL), and sBP (133; 94 to 180 mm Hg) were established for healthy nonbrachycephalic dogs at 1,535-m altitude. All aBG measurements were statistically and clinically different from those previously reported for dogs at sea level. Brachycephalic dogs had significantly lower Pao2 and Sao2 (P = .0150 and P = .0237, respectively) and significantly higher ctHb (P = .0396) compared to nonbrachycephalic dogs acclimatized to the same altitude; the nonbrachycephalic RIs were not transferable to the brachycephalic dogs for Pao2.
CLINICAL RELEVANCE
This study represents the first collation of aBG measurements for healthy nonbrachycephalic dogs acclimatized to an altitude of 1,535 m. Additionally, this study identified differences in arterial oxygenation measurements between brachycephalic and nonbrachycephalic dogs. RIs in brachycephalic dogs need to be established.
Topics: Dogs; Animals; Altitude; Blood Gas Analysis; Craniosynostoses; Oxygen; Carbon Dioxide; Dog Diseases
PubMed: 38320399
DOI: 10.2460/ajvr.23.10.0240 -
Stem Cell Research Apr 2024Sotos syndrome (SoS) is a neurodevelopmental disorder that results from NSD1 mutations that cause haploinsufficiency of NSD1. Here, we generated an induced pluripotent...
Sotos syndrome (SoS) is a neurodevelopmental disorder that results from NSD1 mutations that cause haploinsufficiency of NSD1. Here, we generated an induced pluripotent stem cell (iPSC) line from fibroblasts of a SoS patient carrying the pathogenic variant (c.1633delA). The cell line shows typical iPSC morphology, high expression of pluripotent markers, normal karyotype, and it differentiates into three germ layers in vitro. This line is a valuable resource for studying pathological pathways involved in SoS.
Topics: Humans; Sotos Syndrome; Induced Pluripotent Stem Cells; Mutation; Exons; Histone-Lysine N-Methyltransferase; Craniosynostoses; Intellectual Disability
PubMed: 38301425
DOI: 10.1016/j.scr.2024.103324 -
Molecular landscape of congenital vertebral malformations: recent discoveries and future directions.Orphanet Journal of Rare Diseases Jan 2024Vertebral malformations (VMs) pose a significant global health problem, causing chronic pain and disability. Vertebral defects occur as isolated conditions or within the... (Review)
Review
Vertebral malformations (VMs) pose a significant global health problem, causing chronic pain and disability. Vertebral defects occur as isolated conditions or within the spectrum of various congenital disorders, such as Klippel-Feil syndrome, congenital scoliosis, spondylocostal dysostosis, sacral agenesis, and neural tube defects. Although both genetic abnormalities and environmental factors can contribute to abnormal vertebral development, our knowledge on molecular mechanisms of numerous VMs is still limited. Furthermore, there is a lack of resource that consolidates the current knowledge in this field. In this pioneering review, we provide a comprehensive analysis of the latest research on the molecular basis of VMs and the association of the VMs-related causative genes with bone developmental signaling pathways. Our study identifies 118 genes linked to VMs, with 98 genes involved in biological pathways crucial for the formation of the vertebral column. Overall, the review summarizes the current knowledge on VM genetics, and provides new insights into potential involvement of biological pathways in VM pathogenesis. We also present an overview of available data regarding the role of epigenetic and environmental factors in VMs. We identify areas where knowledge is lacking, such as precise molecular mechanisms in which specific genes contribute to the development of VMs. Finally, we propose future research avenues that could address knowledge gaps.
Topics: Humans; Spine; Abnormalities, Multiple; Klippel-Feil Syndrome; Scoliosis; Hernia, Diaphragmatic
PubMed: 38291488
DOI: 10.1186/s13023-024-03040-0