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Orphanet Journal of Rare Diseases May 2024Trigonocephaly occurs due to the premature fusion of the metopic suture, leading to a triangular forehead and hypotelorism. This condition often requires surgical...
BACKGROUND
Trigonocephaly occurs due to the premature fusion of the metopic suture, leading to a triangular forehead and hypotelorism. This condition often requires surgical correction for morphological and functional indications. Metopic ridges also originate from premature metopic closure but are only associated with mid-frontal bulging; their surgical correction is rarely required. Differential diagnosis between these two conditions can be challenging, especially in minor trigonocephaly.
METHODS
Two hundred seven scans of patients with trigonocephaly (90), metopic rigdes (27), and controls (90) were collected. Geometric morphometrics were used to quantify skull and orbital morphology as well as the interfrontal angle and the cephalic index. An innovative method was developed to automatically compute the frontal curvature along the metopic suture. Different machine-learning algorithms were tested to assess the predictive power of morphological data in terms of classification.
RESULTS
We showed that control patients, trigonocephaly and metopic rigdes have distinctive skull and orbital shapes. The 3D frontal curvature enabled a clear discrimination between groups (sensitivity and specificity > 92%). Furthermore, we reached an accuracy of 100% in group discrimination when combining 6 univariate measures.
CONCLUSION
Two diagnostic tools were proposed and demonstrated to be successful in assisting differential diagnosis for patients with trigonocephaly or metopic ridges. Further clinical assessments are required to validate the practical clinical relevance of these tools.
Topics: Humans; Craniosynostoses; Female; Male; Infant; Imaging, Three-Dimensional; Skull
PubMed: 38762603
DOI: 10.1186/s13023-024-03197-8 -
Nature Biotechnology May 2024
Topics: Humans; Long QT Syndrome; Autistic Disorder; Syndactyly; Genetic Therapy; Mutation
PubMed: 38760554
DOI: 10.1038/s41587-024-02258-4 -
Human Genetics Jun 2024Histone deacetylases (HDACs) are enzymes pivotal for histone modification (i.e. acetylation marks removal), chromatin accessibility and gene expression regulation. Class...
Histone deacetylases (HDACs) are enzymes pivotal for histone modification (i.e. acetylation marks removal), chromatin accessibility and gene expression regulation. Class I HDACs (including HDAC1, 2, 3, 8) are ubiquitously expressed and they often participate in multi-molecular protein complexes. To date, three neurodevelopmental disorders caused by mutations in genes encoding for HDACs (HDAC4, HDAC6 and HDAC8) and thus belonging to the group of chromatinopathies, have been described. We performed whole exome sequencing (WES) for a patient (#249) clinically diagnosed with the chromatinopathy Rubinstein-Taybi syndrome (RSTS) but negative for mutations in RSTS genes, identifying a de novo frameshift variant in HDAC2 gene. We then investigated its molecular effects in lymphoblastoid cell lines (LCLs) derived from the patient compared to LCLs from healthy donors (HD). As the variant was predicted to be likely pathogenetic and to affect the sequence of nuclear localization signal, we performed immunocytochemistry and lysates fractionation, observing a nuclear mis-localization of HDAC2 compared to HD LCLs. In addition, HDAC2 total protein abundance resulted altered in patient, and we found that newly identified variant in HDAC2 affects also acetylation levels, with significant difference in acetylation pattern among patient #249, HD and RSTS cells and in expression of a known molecular target. Remarkably, RNA-seq performed on #249, HD and RSTS cells shows differentially expressed genes (DEGs) common to #249 and RSTS. Interestingly, our reported patient was clinically diagnosed with RSTS, a chromatinopathy which known causative genes encode for enzymes antagonizing HDACs. These results support the role of HDAC2 as causative gene for chromatinopathies, strengthening the genotype-phenotype correlations in this relevant group of disorders.
Topics: Humans; Histone Deacetylase 2; Exome Sequencing; Acetylation; Rubinstein-Taybi Syndrome; Chromatin; Male; Female; Mutation; Frameshift Mutation; Cell Line
PubMed: 38753158
DOI: 10.1007/s00439-024-02675-0 -
BMJ Case Reports May 2024The duplicated origin of the vertebral artery (VA) is an uncommon anatomical variant, which is generally identified incidentally during angiography and can be...
The duplicated origin of the vertebral artery (VA) is an uncommon anatomical variant, which is generally identified incidentally during angiography and can be misdiagnosed as dissection in the setting of posterior circulation stroke. Here, we describe a case of the right V1 VA duplication with embryological aspects in a patient with Klippel-Feil anomaly, which was diagnosed during preoperative evaluation. Surgeons must be aware to avoid vascular injury from a duplicated VA before head-neck and spinal surgery.
Topics: Humans; Klippel-Feil Syndrome; Vertebral Artery; Male; Adult; Computed Tomography Angiography; Female
PubMed: 38749522
DOI: 10.1136/bcr-2024-260605 -
Clinical Neurology and Neurosurgery Jul 2024Craniosynostosis, a developmental craniofacial anomaly, can impair brain development and cause abnormal skull shape due to premature closure of one or more cranial... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Craniosynostosis, a developmental craniofacial anomaly, can impair brain development and cause abnormal skull shape due to premature closure of one or more cranial sutures. Traditional surgical treatments have evolved from open operations to minimally invasive endoscopic techniques. This systematic review and meta-analysis aim to evaluate the effectiveness and safety of the endoscopic approach in craniosynostosis correction.
METHODS
Adhering to Cochrane Group standards and the PRISMA framework, this review utilized databases like PubMed, Embase, and Web of Science, focusing on clinical and surgical outcomes of endoscopic craniosynostosis operations up to December 2023. Inclusion criteria emphasized studies with at least five patients undergoing endoscopic procedures, while exclusion criteria involved non-English papers, incomplete texts, and overlapping data. Statistical analysis used R software with various packages, and methodological bias was assessed using the ROBINS-I framework.
RESULTS
The review included 30 studies (4 prospective, 26 retrospective) with 2561 patients. The median age at operation was 3.20 months. Findings showed a mean operative time of 68.06 min, median hospital stay of 1.28 days, and mean blood loss of 29.89 ml. Blood transfusion was required in 9.97% of cases. Helmet therapy post-operation was common, with a median duration of 9 months. The rate of postoperative complications was 1.86%, and the reoperation rate was 3.07%. No procedure-related mortality was observed. The study noted substantial variations in the handling of craniosynostosis and a lack of consensus on the optimal timing and surgical approach.
CONCLUSION
Endoscopic techniques for craniosynostosis repair demonstrate safety and effectiveness, characterized by low complication risks and favorable surgical outcomes. However, due to the limitations of observational studies and inherent heterogeneity, further comprehensive and controlled trials are needed to validate these findings and understand the long-term outcomes of the endoscopic approach.
Topics: Craniosynostoses; Humans; Neuroendoscopy; Treatment Outcome; Postoperative Complications; Endoscopy; Infant; Operative Time; Length of Stay
PubMed: 38749357
DOI: 10.1016/j.clineuro.2024.108296 -
Anais Da Academia Brasileira de Ciencias 2024Brachycephalic breeds of dogs, most of which show signs of the brachycephalic syndrome may have greater parasympathetic stimulation than other breeds, leading to higher...
Brachycephalic breeds of dogs, most of which show signs of the brachycephalic syndrome may have greater parasympathetic stimulation than other breeds, leading to higher values of heart rate variability and vagal tone index. The aim of this study was to establish a computerized electrocardiographic study and an assessment of the vagus sympathetic balance through heart rate variability and vagal tone index of five brachycephalic breeds compared to mesocephalic dogs. Sixty dogs were used, divided into groups made up of Boxers, English Bulldogs, French Bulldogs, Pugs, Shih-Tzu and no defined breed mesocephalic dogs. Statistical analysis was carried out using the Shapiro-Wilk test, Kruskal-Wallis and Dunn's test or ANOVA and Bonferroni (p<0.05). In the evaluation of vagal sympathetic balance among all the dogs, there was a negative correlation between heart rate and HRV 10RR (r = - 0.7678; p < 0.0001), HRV 20RR (r = - 0.8548, p < 0.0001) and VVTI (r = - 0.2770; p = 0.0321). It can therefore be concluded that the dog's breed and morphology did not alter its electrocardiographic parameters or heart rate variability. The vagal tone index, which in other studies differed in brachycephalic dogs, showed no difference when compared separately in brachycephalic breeds.
Topics: Animals; Dogs; Heart Rate; Vagus Nerve; Electrocardiography; Male; Female; Craniosynostoses
PubMed: 38747800
DOI: 10.1590/0001-3765202420231250 -
The Journal of Craniofacial Surgery Jun 2024Metopic craniosynostosis (MCS) can be difficult to differentiate from metopic ridge (MR) or normal frontal morphology. This study assess whether the supraorbital...
OBJECTIVE
Metopic craniosynostosis (MCS) can be difficult to differentiate from metopic ridge (MR) or normal frontal morphology. This study assess whether the supraorbital notch-nasion-supraorbital notch (SNS) angle can help identify MCS.
METHODS
Records of 212 patients with preoperative three-dimensional computed tomography scans were examined. The SNS angles, surgeon craniofacial dysmorphology rankings, and CranioRate metopic severity scores (MSSs) were compared with the Spearman rank correlation coefficient. Receiver operating characteristic (ROC) curves with Youden J-statistic and cross-validation of regression models assessed the ability of these measures to predict surgery.
RESULTS
A total of 212 patients were included, consisting of 78 MCS, 37 MR, and 97 controls. Both the mean SNS angle (MCS: 111.7 ± 10.7 degrees, MR: 126.0 ± 8.2 degrees, controls: 130.7 ± 8.8 degrees P < 0.001) and MSS (MCS: 5.9 ± 2.0, MR: 1.4 ± 1.9, controls: 0.2 ± 1.9, P < 0.001) were different among the cohorts. The mean SNS angle (111.5 ± 10.7 versus 129.1 ± 8.8, P < 0.001) was lower in those who had surgery and CranioRate score (5.9 ± 2.1 versus 0.8 ± 2.2, P < 0.001) was higher in those who underwent surgery. SNS angles were positively correlated with surgeon craniofacial dysmorphology rankings ( r = 0.41, P < 0.05) and CranioRate MSS ( r = 0.54, P < 0.05). The ROC curve requiring high sensitivity revealed an SNS angle of 124.8 degrees predicted surgery with a sensitivity of 88.7% and a specificity of 71.3%. A ROC curve using the CranioRate MCC values ≥3.19 predicted surgery with 88.7% sensitivity and 94.7% specificity.
CONCLUSION
Orbital dysmorphology in patients with MCS is well captured by the supraorbital-nasion angle. Both the SNS angle and CranioRate MSS scores accurately predict surgical intervention.
Topics: Female; Humans; Infant; Male; Craniosynostoses; Imaging, Three-Dimensional; Orbit; Reproducibility of Results; Retrospective Studies; ROC Curve; Severity of Illness Index; Tomography, X-Ray Computed
PubMed: 38743289
DOI: 10.1097/SCS.0000000000010302 -
Lancet (London, England) May 2024
Topics: Humans; Bone Diseases, Developmental; Bone Marrow Transplantation; Craniofacial Abnormalities; Hyperostosis; Hypertelorism; Osteochondrodysplasias; Transplantation, Homologous; Female; Child, Preschool
PubMed: 38734477
DOI: 10.1016/S0140-6736(24)00803-1 -
International Journal of Molecular... Apr 2024Hemifacial microsomia (HFM) is a rare congenital genetic syndrome primarily affecting the first and second pharyngeal arches, leading to defects in the mandible,...
Hemifacial microsomia (HFM) is a rare congenital genetic syndrome primarily affecting the first and second pharyngeal arches, leading to defects in the mandible, external ear, and middle ear. The pathogenic genes remain largely unidentified. Whole-exome sequencing (WES) was conducted on 12 HFM probands and their unaffected biological parents. Predictive structural analysis of the target gene was conducted using PSIPRED (v3.3) and SWISS-MODEL, while STRING facilitated protein-to-protein interaction predictions. CRISPR/Cas9 was applied for gene knockout in zebrafish. In situ hybridization (ISH) was employed to examine the spatiotemporal expression of the target gene and neural crest cell (NCC) markers. Immunofluorescence with PH3 and TUNEL assays were used to assess cell proliferation and apoptosis. RNA sequencing was performed on mutant and control embryos, with rescue experiments involving target mRNA injections and specific gene knockouts. was identified as a novel candidate gene for HFM, with four nonsynonymous de novo variants detected in three unrelated probands. Structural predictions indicated significant alterations in the secondary and tertiary structures of . knockout in zebrafish resulted in craniofacial malformation, spine deformity, and cardiac edema, mirroring typical HFM phenotypes. Abnormalities in somatic cell apoptosis, reduced NCC proliferation in pharyngeal arches, and chondrocyte differentiation issues were observed in mutants. mRNA injections and or knockout significantly rescued pharyngeal arch cartilage dysplasia, while mRNA administration partially restored the defective phenotypes. Our findings suggest a functional link between and HFM, primarily through the inhibition of proliferation and disruption of pharyngeal chondrocyte differentiation.
Topics: Animals; Zebrafish; Humans; Male; Female; Goldenhar Syndrome; Apoptosis; Neural Crest; Exome Sequencing; Cell Proliferation; Phenotype; Mutation; Gene Knockout Techniques
PubMed: 38731925
DOI: 10.3390/ijms25094707 -
The Journal of Hand Surgery... Jun 2024Ectodermal dysplasia-syndactyly syndrome 1 (EDSS1) is an exceedingly rare condition associated with mutations in the PVL4 gene. It is characterised by sparse, brittle...
Ectodermal dysplasia-syndactyly syndrome 1 (EDSS1) is an exceedingly rare condition associated with mutations in the PVL4 gene. It is characterised by sparse, brittle hair, eyebrows and eyelashes, abnormal dentition and nails, along with bilateral cutaneous syndactyly involving the fingers and toes. We report a 2-year-old girl who presented to us with bilateral complete simple syndactyly of the third and fourth web spaces of the hands, along with bilateral syndactyly of both feet involving the second to fourth toes. Upon examination, sparse hair and eyebrows, along with abnormal dentition, were noted. Thorough clinical examination and genetic analysis were conducted on the affected child and her father, who exhibited similar clinical features. Genetic analysis revealed a homozygous nonsense mutation in the PVL4 gene in both individuals. According to the literature, EDSS1 has been reported in only 10 families worldwide, and there are no reported cases from India. Level V (Therapeutic).
Topics: Child, Preschool; Female; Humans; Codon, Nonsense; Ectodermal Dysplasia; Syndactyly
PubMed: 38726487
DOI: 10.1142/S242483552472007X