RESUMO
Pulmonary arteriovenous malformations (PAVMs) are vascular anomalies resulting in abnormal connections between pulmonary arteries and veins. In 80% of cases, PAVMs are present from birth, but clinical manifestations are rarely seen in childhood. These congenital malformations are typically associated with Hereditary Hemorrhagic Telangiectasia (HHT), a rare disease that affects 1 in 5000/8000 individuals. HHT disease is frequently caused by mutations in genes involved in the TGF-ß pathway. However, approximately 15% of patients do not have a genetic diagnosis and, among the genetically diagnosed, more than 33% do not meet the Curaçao criteria. This makes clinical diagnosis even more challenging in the pediatric age group. Here, we introduce an 8-year-old patient bearing a severe phenotype of multiple diffuse PAVMs caused by an unknown mutation which ended in lung transplantation. Phenotypically, the case under study follows a molecular pattern which is HHT-like. Therefore, molecular- biological and cellular-functional analyses have been performed in primary endothelial cells (ECs) isolated from the explanted lung. The findings revealed a loss of functionality in lung endothelial tissue and a stimulation of endothelial-to-mesenchymal transition. Understanding the molecular basis of this transition could potentially offer new therapeutic strategies to delay lung transplantation in severe cases.
Assuntos
Células Endoteliais , Artéria Pulmonar , Veias Pulmonares , Telangiectasia Hemorrágica Hereditária , Humanos , Telangiectasia Hemorrágica Hereditária/genética , Telangiectasia Hemorrágica Hereditária/patologia , Criança , Artéria Pulmonar/anormalidades , Artéria Pulmonar/patologia , Veias Pulmonares/anormalidades , Veias Pulmonares/patologia , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Masculino , Mutação , Malformações Arteriovenosas/genética , Malformações Arteriovenosas/patologia , Malformações Arteriovenosas/metabolismo , Transição Epitelial-Mesenquimal/genética , Transplante de Pulmão , Fístula Arteriovenosa/patologia , Fístula Arteriovenosa/genética , Pulmão/patologia , Pulmão/irrigação sanguínea , FemininoRESUMO
Clinical outcomes of arteriovenous fistulae (AVF) for hemodialysis remain inadequate since biological mechanisms of AVF maturation and failure are still poorly understood. Aortocaval fistula creation (AVF group) or a sham operation (sham group) was performed in C57BL/6 mice. Venous limbs were collected on postoperative day 7 and total RNA was extracted for high throughput RNA sequencing and bioinformatic analysis. Genes in metabolic pathways were significantly downregulated in the AVF, whereas significant sex differences were not detected. Since gene expression patterns among the AVF group were heterogenous, the AVF group was divided into a 'normal' AVF (nAVF) group and an 'outliers' (OUT) group. The gene expression patterns of the nAVF and OUT groups were consistent with previously published data showing venous adaptive remodeling, whereas enrichment analyses showed significant upregulation of metabolism, inflammation and coagulation in the OUT group compared to the nAVF group, suggesting the heterogeneity during venous remodeling reflects early gene expression changes that may correlate with AVF maturation or failure. Early detection of these processes may be a translational strategy to predict fistula failure and reduce patient morbidity.
Assuntos
Derivação Arteriovenosa Cirúrgica , Camundongos Endogâmicos C57BL , Remodelação Vascular , Animais , Camundongos , Masculino , Remodelação Vascular/genética , Feminino , Regulação para Baixo/genética , Veias/metabolismo , Diálise Renal , Fístula Arteriovenosa/genética , Fístula Arteriovenosa/metabolismo , Fístula Arteriovenosa/patologia , Regulação da Expressão Gênica , Perfilação da Expressão GênicaRESUMO
Arteriovenous fistulas (AVFs) are the most common vascular access points for hemodialysis (HD), but they have a high incidence of postoperative dysfunction, mainly due to excessive neointimal hyperplasia (NIH). Our previous studies have revealed a highly conserved LncRNA-LncDACH1 as an important regulator of cardiomyocyte and fibroblast proliferation. Herein, we find that LncDACH1 regulates NIH in AVF in male mice with conditional knockout of smooth muscle cell-specific LncDACH1 and in male mice model of AVF with LncDACH1 overexpression by adeno-associated virus. Mechanistically, silence of LncDACH1 activates p-AKT through promoting the expression of heat shock protein 90 (HSP90) and serine/arginine-rich splicing factor protein kinase 1 (SRPK1). Moreover, LncDACH1 is transcriptionally activated by transcription factor KLF9 that binds directly to the promoter region of the LncDACH1 gene. In this work, during AVF NIH, LncDACH1 is downregulated by KLF9 and promotes NIH through the HSP90/ SRPK1/ AKT signaling axis.
Assuntos
Proteínas de Choque Térmico HSP90 , Hiperplasia , Fatores de Transcrição Kruppel-Like , Miócitos de Músculo Liso , Neointima , Proteínas Proto-Oncogênicas c-akt , RNA Longo não Codificante , Animais , Humanos , Masculino , Camundongos , Fístula Arteriovenosa/metabolismo , Fístula Arteriovenosa/genética , Fístula Arteriovenosa/patologia , Proliferação de Células , Proteínas de Choque Térmico HSP90/metabolismo , Proteínas de Choque Térmico HSP90/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Fatores de Transcrição Kruppel-Like/genética , Camundongos Endogâmicos C57BL , Camundongos Knockout , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Neointima/patologia , Neointima/metabolismo , Fenótipo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de SinaisRESUMO
Jumonji domain-containing protein-3 (JMJD3), a histone H3 lysine 27 (H3K27) demethylase, promotes endothelial regeneration, but its function in neointimal hyperplasia (NIH) of arteriovenous fistulas (AVFs) has not been explored. In this study, we examined the contribution of endothelial JMJD3 to NIH of AVFs and the mechanisms underlying JMJD3 expression during kidney failure. We found that endothelial JMJD3 expression was negatively associated with NIH of AVFs in patients with kidney failure. JMJD3 expression in endothelial cells (ECs) was also downregulated in the vasculature of chronic kidney disease (CKD) mice. In addition, specific knockout of endothelial JMJD3 delayed EC regeneration, enhanced endothelial mesenchymal transition, impaired endothelial barrier function as determined by increased Evans blue staining and inflammatory cell infiltration, and accelerated neointima formation in AVFs created by venous end to arterial side anastomosis in CKD mice. Mechanistically, JMJD3 expression was downregulated via binding of transforming growth factor beta 1-mediated Hes family transcription factor Hes1 to its gene promoter. Knockdown of JMJD3 enhanced H3K27 methylation, thereby inhibiting transcriptional activity at promoters of EC markers and reducing migration and proliferation of ECs. Furthermore, knockdown of endothelial JMJD3 decreased endothelial nitric oxide synthase expression and nitric oxide production, leading to the proliferation of vascular smooth muscle cells. In conclusion, we demonstrate that decreased expression of endothelial JMJD3 impairs EC regeneration and function and accelerates neointima formation in AVFs. We propose increasing the expression of endothelial JMJD3 could represent a new strategy for preventing endothelial dysfunction, attenuating NIH, and improving AVF patency in patients with kidney disease.
Assuntos
Fístula Arteriovenosa , Histona Desmetilases com o Domínio Jumonji/genética , Insuficiência Renal Crônica , Animais , Fístula Arteriovenosa/genética , Fístula Arteriovenosa/patologia , Regulação para Baixo , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Humanos , Hiperplasia/genética , Hiperplasia/patologia , Histona Desmetilases com o Domínio Jumonji/metabolismo , Camundongos , Neointima/genéticaRESUMO
Arteriovenous fistulas are the ideal form of vascular access that allows provision of haemodialysis. Stenotic lesions caused by neointimal hyperplasia commonly occur resulting in patients requiring a fistuloplasty. This is effective but there is a high recurrence rate. We sought to investigate the effects of a fistuloplasty on monocyte populations. Blood samples were taken from patients before and after their fistuloplasty procedure. Samples were analysed using flow cytometry, ELISA and Luminex assays. Univariate cox regression was carried out to investigate associations with post fistuloplasty patency. At 1-2 days post fistuloplasty, the proportion of classical (CD14++CD16-) monocytes decreased (p < 0.001), whilst intermediate (CD14++CD16+) and non-classical (CD14+CD16+) monocytes increased (both p < 0.01) in a cohort of 20 patients. A time course study carried out in 5 patients showed that this was due to an increase in absolute numbers of non-classical and intermediate monocytes. Higher levels of non-classical monocytes pre-fistuloplasty were associated with an increased risk for patency loss (p < 0.05). We measured 41 soluble factors in plasma samples taken before a fistuloplasty in 54 patients, with paired post-fistuloplasty samples (1-2 days) available in 30 patients. After correcting for false discovery, the only factor with a significant change in level was IL-6 (P = 0.0003, q = 0.0124). In a further time-course study in 6 patients, peak level of IL-6 occurred 2-3 h post fistuloplasty. This study demonstrates that there is a systemic inflammatory response to the fistuloplasty procedure and that monocyte subsets and IL-6 may be important in the pathophysiology of restenosis.
Assuntos
Fístula Arteriovenosa/genética , Hiperplasia/genética , Interleucina-6/genética , Monócitos/metabolismo , Receptores de IgG/genética , Insuficiência Renal Crônica/genética , Idoso , Angioplastia/métodos , Fístula Arteriovenosa/mortalidade , Fístula Arteriovenosa/patologia , Fístula Arteriovenosa/cirurgia , Biomarcadores/metabolismo , Feminino , Proteínas Ligadas por GPI/genética , Proteínas Ligadas por GPI/metabolismo , Expressão Gênica , Humanos , Hiperplasia/metabolismo , Hiperplasia/patologia , Hiperplasia/cirurgia , Interleucina-6/metabolismo , Receptores de Lipopolissacarídeos/genética , Receptores de Lipopolissacarídeos/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/patologia , Neointima/metabolismo , Neointima/patologia , Receptores de IgG/metabolismo , Recidiva , Diálise Renal/métodos , Diálise Renal/mortalidade , Insuficiência Renal Crônica/mortalidade , Insuficiência Renal Crônica/patologia , Insuficiência Renal Crônica/cirurgia , Análise de SobrevidaRESUMO
BACKGROUND: The mechanisms of brain arteriovenous malformation (bAVM) development, formation, and progress are still poorly understood. By gaining more knowledge about the molecular signature of bAVM in relation to hemorrhage, we might be able to find biomarkers associated with this serious complication, which can function as a goal for further research and can be a potential target for gene therapy. AIMS: To provide a comprehensive overview of the molecular signature of bAVM-related hemorrhage We conducted a systematic review, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, of articles published in Embase, Medline, Cochrane central, Scopus, and Chinese databases (CNKI, Wanfang). SUMMARY OF REVIEW: Our search identified 3944 articles, of which 3108 remained after removal of duplicates. After title, abstract, and full-text screening, 31 articles were included for analysis. The results show an overview of molecular characteristics. Several genetic polymorphisms are identified that increase the risk of bAVM rupture by increasing the expression of certain inflammatory cytokines (interleukin [IL]-6, IL-17A, IL-1ß, and tumor necrosis factor-α), NOTCH pathways, matrix metalloproteinase-9, and vascular endothelial growth factor-α. CONCLUSIONS: Several molecular factors are associated with the risk of bAVM-related hemorrhage. These factors are associated with increased inflammation on the cellular level and changes in the endothelium leading to instability of the vessel wall. Further investigation of these biomarkers regarding hemorrhage rates, together with their relationship with noninvasive diagnostic methods, should be a goal of future studies to improve the patient specific risk estimation and future treatment options.
Assuntos
Fístula Arteriovenosa/complicações , Fístula Arteriovenosa/genética , Hemorragia Cerebral/genética , Malformações Arteriovenosas Intracranianas/complicações , Malformações Arteriovenosas Intracranianas/genética , Humanos , Polimorfismo GenéticoRESUMO
PURPOSE: Dural arteriovenous fistulae (dAVF) are an uncommon feature of PTEN hamartoma tumor syndrome (PHTS). We report a case of an adolescent male diagnosed with PHTS following the treatment of multiple intracranial dAVF to emphasize the association of vascular anomalies with this disorder and discuss potential implications. CASE REPORT: An adolescent male presented with bilateral proptosis secondary to intracranial venous hypertension. Workup revealed the presence of a complex intracranial dAVF which was treated with several embolization procedures. Following treatment, a de novo dAVF was identified on surveillance imaging. A genetic workup revealed a pathogenic mutation in PTEN consistent with a diagnosis of PHTS. CONCLUSIONS: Recognition that PHTS may be associated with dAVF, and potentially delayed spontaneous formation of dAVF, is critically important due to the potential for devastating yet preventable neurologic sequelae.
Assuntos
Fístula Arteriovenosa , Malformações Vasculares do Sistema Nervoso Central , Embolização Terapêutica , Síndrome do Hamartoma Múltiplo , Adolescente , Fístula Arteriovenosa/complicações , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/genética , Malformações Vasculares do Sistema Nervoso Central/complicações , Criança , Síndrome do Hamartoma Múltiplo/complicações , Síndrome do Hamartoma Múltiplo/diagnóstico por imagem , Síndrome do Hamartoma Múltiplo/genética , Humanos , Masculino , PTEN Fosfo-Hidrolase/genéticaRESUMO
Vertebro-Vertebral arteriovenous fistula (VV-AVF) associated with neurofibromatosis Type I (NF-1) is rare. We presented two female NF-1 patients with a diagnosis of VV-AVF treated with endovascular approach. The fistula was completely obliterated with balloon assisted embolization and covered stent separately and VA patency was preserved in both cases. Reviewing the literature with a focus on endovascular treatment, endovascular occlusion of VV-AVF in NF-1 patients is safe and effective. To preserve the parent VA patency and obliterate the fistula simultaneously is challenging generally, but feasible in some cases.
Assuntos
Fístula Arteriovenosa/genética , Fístula Arteriovenosa/terapia , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Neurofibromatose 1/complicações , Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Artéria Vertebral/anormalidades , Artéria Vertebral/cirurgiaRESUMO
Matrix metalloproteinase 9 (MMP-9) expression is upregulated in vascular inflammation and participates in vascular remodeling, including aneurysm dilatation and arterial neointima development. Neointima at the arteriovenous (AV) fistula anastomosis site primarily causes AV fistula stenosis and failure; however, the effects of MMP-9 on perioperative AV fistula remodeling remain unknown. Therefore, we created AV fistulas (end-to-side anastomosis) in wild-type (WT) and MMP-9 knockout mice with chronic kidney disease to further clarify this. Neointima progressively developed in the AV fistula venous segment of WT mice during the four-week postoperative course, and MMP-9 knockout increased the lumen area and attenuated neointima size by reducing smooth muscle cell and collagen components. Early perioperative AV fistula mRNA sequencing data revealed that inflammation-related gene sets were negatively enriched in AV fistula of MMP-9 knockout mice compared to that in WT mice. qPCR results also showed that inflammatory genes, including tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1), were downregulated. In addition, Western blot results showed that MMP-9 knockout reduced CD44 and RAC-alpha serine/threonine-protein kinase (Akt) and extracellular signal-regulated kinases (ERK) phosphorylation. In vitro, MMP-9 addition enhanced IL-6 and MCP-1 expression in vascular smooth muscle cells, as well as cell migration, which was reversed by an MMP-9 inhibitor. In conclusion, MMP-9 knockout attenuated AV fistula stenosis by reducing perioperative vascular inflammation.
Assuntos
Fístula Arteriovenosa/genética , Inflamação/genética , Metaloproteinase 9 da Matriz/genética , Neointima/genética , Animais , Movimento Celular/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/patologia , Período Perioperatório , Remodelação Vascular/genéticaRESUMO
Pial arteriovenous fistulas (AVFs) are rare vascular lesions; their exact pathophysiology is largely unknown. Pial AVFs have been reported to develop within capillary malformation-arteriovenous malformation (CM-AVM); however, only a few cases have been reported. Variants in the RASA1 gene have been reported as a cause of CM-AVM. We report the case of an adult patient with pial AVF, who carried variants in the RASA1 and COL4A2 genes. The patient in the current report was likely to have been affected by CM-AVM and the RASA1 variant seemed to be the primary factor in the pathogenesis of pial AVF. However, COL4A2 may have also contributed to the development of pial AVF because the COL4A2 and RASA1 variants have a common pathophysiology, wherein the patient develops lesions due to collagen type IV deficiency.
Assuntos
Fístula Arteriovenosa/genética , Malformações Arteriovenosas/genética , Capilares/anormalidades , Colágeno Tipo IV/genética , Mancha Vinho do Porto/genética , Proteína p120 Ativadora de GTPase/genética , Adulto , Fístula Arteriovenosa/diagnóstico por imagem , Malformações Arteriovenosas/diagnóstico por imagem , Capilares/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Mancha Vinho do Porto/diagnóstico por imagemRESUMO
In this retrospective single-center study, we evaluated whether/how pathogenic/likely pathogenic variants of three hereditary hemorrhagic telangiectasia (HHT)-associated genes (ENG, ACVRL1, and SMAD4) are associated with specific clinical presentations of HHT. We also characterized the morphological features of pulmonary arteriovenous malformations (AVMs) in patients with these variants. Pathogenic or likely pathogenic variants were detected in 64 patients. Using nonparametric statistical tests, we compared the type and prevalence of specific HHT diagnostic features associated with these three variants. Pathogenic variants in these genes resulted in gene-specific HHT clinical presentations. Epistaxis was present in 93%, 94%, and 100% of patients with ENG, ACVRL1, and SMAD4 variants, respectively (p = 0.79). Pulmonary AVMs were more common in patients with the ENG variant (p = 0.034) compared with other subgroups. ACVRL1 variant was associated with the lowest frequency of pulmonary AVMs (p = 0.034) but the highest frequency of hepatic AVMs (p = 0.015). Patients with the ACVRL1 variant did not have significantly more pancreatic AVMs compared with the other groups (p = 0.72). ENG, ACVRL1, and SMAD4 pathogenic or likely pathogenic variants are associated with gene-specific HHT presentations, which is consistent with results from other HHT centers.
Assuntos
Receptores de Activinas Tipo II/genética , Fístula Arteriovenosa/genética , Endoglina/genética , Artéria Pulmonar/anormalidades , Veias Pulmonares/anormalidades , Proteína Smad4/genética , Telangiectasia Hemorrágica Hereditária/genética , Adulto , Fístula Arteriovenosa/complicações , Fístula Arteriovenosa/patologia , Feminino , Predisposição Genética para Doença , Fator 2 de Diferenciação de Crescimento/genética , Humanos , Masculino , Mutação/genética , Artéria Pulmonar/patologia , Veias Pulmonares/patologia , Estudos Retrospectivos , Telangiectasia Hemorrágica Hereditária/patologia , Proteína p120 Ativadora de GTPase/genéticaRESUMO
Percutaneous transluminal angioplasty (PTA) of stenotic arteriovenous fistulas (AVFs) is performed to maintain optimal function and patency. The one-year patency rate is 60% because of venous neointimal hyperplasia (VNH) and venous stenosis (VS) formation. Immediate early response gene X-1 (Iex-1) also known as Ier3 increases in response to wall shear stress (WSS), and can cause VNH/VS formation in murine AVF. In human stenotic samples from AVFs, we demonstrated increased gene expression of Ier3. We hypothesized that 1α, 25-dihydroxyvitamin D3, an inhibitor of IER3 delivered as 1α, 25-dihydroxyvitamin D3 encapsulated in poly lactic-co-glycolic acid (PLGA) nanoparticles loaded in Pluronic F127 hydrogel (1,25 NP) to the adventitia of the stenotic outflow vein after PTA would decrease VNH/VS formation by reducing Ier3 and chemokine (C-C motif) ligand 2 (Ccl2) expression. In our murine model of AVF stenosis treated with PTA, increased expression of Ier3 and Ccl2 was observed. Using this model, PTA was performed and 10-µL of 1,25 NP or control vehicle (PLGA in hydrogel) was administered by adventitial delivery. Animals were sacrificed at day 3 for unbiased whole genome transcriptomic analysis and at day 21 for immunohistochemical analysis. Doppler US was performed weekly after AVF creation. At day 3, significantly lower gene expression of Ier3 and Ccl2 was noted in 1,25 NP treated vessels. Twenty-one days after PTA, 1,25 NP treated vessels had increased lumen vessel area, with decreased neointima area/media area ratio and cell density compared to vehicle controls. There was a significant increase in apoptosis, with a reduction in CD68, F4/80, CD45, pro-inflammatory macrophages, fibroblasts, Picrosirius red, Masson's trichrome, collagen IV, and proliferation accompanied with higher wall shear stress (WSS) and average peak velocity. IER3 staining was localized to CD68 and FSP-1 (+) cells. After 1,25 NP delivery, there was a decrease in the proliferation of α-SMA (+) and CD68 (+) cells with increase in the apoptosis of FSP-1 (+) and CD68 (+) cells compared to vehicle controls. RNA sequencing revealed a decrease in inflammatory and apoptosis pathways following 1,25 NP delivery. These data suggest that adventitial delivery of 1,25 NP reduces VNH and venous stenosis formation after PTA.
Assuntos
Angioplastia , Fístula Arteriovenosa/terapia , Calcitriol/administração & dosagem , Constrição Patológica/tratamento farmacológico , Vitaminas/administração & dosagem , Adulto , Túnica Adventícia/metabolismo , Idoso , Angioplastia/efeitos adversos , Animais , Proteínas Reguladoras de Apoptose/antagonistas & inibidores , Proteínas Reguladoras de Apoptose/genética , Fístula Arteriovenosa/genética , Calcitriol/uso terapêutico , Constrição Patológica/genética , Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Feminino , Humanos , Masculino , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/genética , Camundongos , Pessoa de Meia-Idade , Nanopartículas/química , Vitaminas/uso terapêuticoRESUMO
BACKGROUND: Brain arteriovenous malformation (BAVM) is a main cause of cerebral hemorrhage and hemorrhagic stroke in adolescents. Morphologically, a BAVM is an abnormal connection between cerebrovascular arteries and veins. The genetic etiology of BAVMs has not been fully elucidated. In this study, we aim to investigate potential recessive genetic variants in BAVMs by interrogation of rare compound heterozygous variants. METHODS: We performed whole exome sequencing (WES) on 112 BAVM trios and analyzed the data for rare and deleterious compound heterozygous mutations associated with the disease. RESULTS: We identified 16 genes with compound heterozygous variants that were recurrent in more than one trio. Two genes (LRP2, MUC5B) were recurrently mutated in three trios. LRP2 has been previously associated with BAVM pathogenesis. Fourteen genes (MYLK, HSPG2, PEAK1, PIEZO1, PRUNE2, DNAH14, DNAH5, FCGBP, HERC2, HMCN1, MYH1, NHSL1, PLEC, RP1L1) were recurrently mutated in two trios, and five of these genes (MYLK, HSPG2, PEAK1, PIEZO1, PRUNE2) have been reported to play a role in angiogenesis or vascular diseases. Additionally, abnormal expression of the MYLK protein is related to spinal arteriovenous malformations. CONCLUSION: Our study indicates that rare recessive compound heterozygous variants may underlie cases of BAVM. These findings improve our understanding of BAVM pathology and indicate genes for functional validation.
Assuntos
Fístula Arteriovenosa/genética , Sequenciamento do Exoma/métodos , Exoma/genética , Variação Genética/genética , Malformações Arteriovenosas Intracranianas/genética , Adolescente , Adulto , Fístula Arteriovenosa/epidemiologia , China/epidemiologia , Proteínas do Olho/genética , Feminino , Humanos , Malformações Arteriovenosas Intracranianas/epidemiologia , Masculino , Adulto JovemAssuntos
Fístula Arteriovenosa/genética , Endoglina/genética , Artéria Pulmonar/anormalidades , Veias Pulmonares/anormalidades , Telangiectasia Hemorrágica Hereditária/genética , Feto Abortado/patologia , Adulto , Fístula Arteriovenosa/complicações , Fístula Arteriovenosa/patologia , Malformações Arteriovenosas/genética , Malformações Arteriovenosas/mortalidade , Malformações Arteriovenosas/fisiopatologia , Feminino , Humanos , Masculino , Mutação/genética , Artéria Pulmonar/patologia , Veias Pulmonares/patologia , Telangiectasia Hemorrágica Hereditária/complicações , Telangiectasia Hemorrágica Hereditária/patologiaAssuntos
Fístula Arteriovenosa , Malformações Arteriovenosas , Abscesso Encefálico , Veias Pulmonares , Telangiectasia Hemorrágica Hereditária , Fístula Arteriovenosa/complicações , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/genética , Malformações Arteriovenosas/complicações , Malformações Arteriovenosas/diagnóstico por imagem , Malformações Arteriovenosas/genética , Abscesso Encefálico/diagnóstico por imagem , Humanos , Artéria Pulmonar/diagnóstico por imagem , Veias Pulmonares/diagnóstico por imagem , Telangiectasia Hemorrágica Hereditária/diagnóstico , Telangiectasia Hemorrágica Hereditária/diagnóstico por imagemRESUMO
Children can have a variety of intracranial vascular anomalies ranging from small and incidental with no clinical consequences to complex lesions that can cause substantial neurologic deficits, heart failure, or profoundly affect development. In contrast to high-flow lesions with direct arterial-to-venous shunts, low-flow lesions such as cavernous malformations are associated with a lower likelihood of substantial hemorrhage, and a more benign course. Management of vascular anomalies in children has to incorporate an understanding of how treatment strategies may affect the normal development of the central nervous system. In this review, we discuss the etiologies, epidemiology, natural history, and genetic risk factors of three high-flow vascular malformations seen in children: brain arteriovenous malformations, intracranial dural arteriovenous fistulas, and vein of Galen malformations.
Assuntos
Fístula Arteriovenosa , Embolização Terapêutica , Malformações Arteriovenosas Intracranianas , Radiocirurgia , Fístula Arteriovenosa/diagnóstico , Fístula Arteriovenosa/etiologia , Fístula Arteriovenosa/genética , Fístula Arteriovenosa/terapia , Criança , Humanos , Malformações Arteriovenosas Intracranianas/diagnóstico , Malformações Arteriovenosas Intracranianas/etiologia , Malformações Arteriovenosas Intracranianas/genética , Malformações Arteriovenosas Intracranianas/terapiaAssuntos
Fístula Arteriovenosa/genética , Malformações Arteriovenosas Intracranianas/genética , Malformações Vasculares , Anormalidades Múltiplas , Idoso , Amaurose Fugaz/etiologia , Fístula Arteriovenosa/complicações , Fístula Arteriovenosa/diagnóstico por imagem , Feminino , Humanos , Malformações Arteriovenosas Intracranianas/complicações , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Masculino , Mutação , Linhagem , Tomografia Computadorizada por Raios XRESUMO
Capillary malformation-arteriovenous malformation syndrome (CM-AVM) is a rare condition associated with mutations in the genes RASA1 and EPHB4. We present a challenging case of CM-AVM in a 17-month-old boy with permanent diplegia from an undiagnosed arteriovenous malformation underlying a large atypical capillary malformation over the lower thoracic spine. This case demonstrates that clinicians should have a low threshold for neuroimaging in the context of new neurologic symptoms in patients with atypical capillary malformations.