Question: You are an expert researcher providing comprehensive, well-cited information.

Provide detailed information focusing on: 1. Key concepts and definitions with current understanding 2. Recent developments and latest research (prioritize 2023-2024 sources) 3. Current applications and real-world implementations 4. Expert opinions and analysis from authoritative sources 5. Relevant statistics and data from recent studies

Format as a comprehensive research report with proper citations. Include URLs and publication dates where available. Always prioritize recent, authoritative sources and provide specific citations for all major claims.

Disease Characteristics Research Template

Target Disease

• Disease Name: Vein of Galen Aneurysm
• MONDO ID: (if available)
• Category: Congenital

Research Objectives

Please provide a comprehensive research report on Vein of Galen Aneurysm covering all of the disease characteristics listed below. This report will be used to populate a disease knowledge base entry. Be thorough and cite primary literature (PMID preferred) for all claims.

For each section, suggested databases/resources are listed. These are the first places you should search for information on each topic.

1. Disease Information

Search first: OMIM, Orphanet, ICD-10/ICD-11, MeSH, PubMed

• What is the disease? Provide a concise overview.
• What are the key identifiers? (OMIM, Orphanet, ICD-10/ICD-11, MeSH, Mondo)
• What are the common synonyms and alternative names?
• Is the information derived from individual patients (e.g., EHR) or aggregated disease-level resources?

2. Etiology

• Disease Causal Factors: What are the primary causes? (genetic, environmental, infectious, mechanistic)
• Risk Factors:

  Search first: PubMed, Cochrane Library, UpToDate, clinical guidelines, ClinVar, ClinGen, GWAS Catalog, PheGenI, CTD, CDC, WHO, epidemiological databases

• Genetic risk factors (causal variants, susceptibility loci, modifier genes)
• Environmental risk factors (toxins, lifestyle, occupational exposures, age, sex, family history)
• Protective Factors:

  Search first: PubMed, Cochrane Library, clinical trial databases, GWAS Catalog, gnomAD, WHO, CDC, nutrition databases

• Genetic protective factors (protective variants, modifier alleles)
• Environmental protective factors (diet, lifestyle, exposures that reduce risk)
• Gene-Environment Interactions: How do genetic and environmental factors interact to influence disease?

  Search first: CTD, PubMed, PheGenI, GxE databases

3. Phenotypes

Search first: HPO (Human Phenotype Ontology), OMIM, Orphanet, PubMed, clinicaltrials.gov, MedDRA, SNOMED CT, DECIPHER, LOINC

For each phenotype, provide: - Phenotype type: symptoms, clinical signs, physical manifestations, behavioral changes, or laboratory abnormalities

For symptoms/signs: HPO, OMIM, Orphanet, PubMed For behavioral changes: HPO, DSM, RDoC (Research Domain Criteria), PubMed For laboratory abnormalities: LOINC, SNOMED CT, LabTests Online, PubMed - Phenotype characteristics: Search first: OMIM, Orphanet, HPO, PubMed - Age of symptom onset (neonatal, childhood, adult-onset, late-onset) - Symptom severity (mild, moderate, severe, variable) - Symptom progression (stable, progressive, episodic, fluctuating) - Frequency among affected individuals (percentage or qualitative) - Quality of life impact: Effects on daily functioning and well-being (per-phenotype when possible) Search first: EQ-5D database, SF-36, WHO QOL databases, PubMed - Suggest HPO (Human Phenotype Ontology) terms for each phenotype

4. Genetic/Molecular Information

• Causal Genes: Gene mutations or chromosomal abnormalities responsible for disease (gene symbols, OMIM IDs)

  Search first: OMIM, ClinVar, HGMD, Ensembl, NCBI Gene

• Pathogenic Variants:
• Affected genes (gene symbols, HGNC IDs) > Search first: OMIM, NCBI Gene, Ensembl, HGNC, UniProt, GeneCards
• Variant classification (pathogenic, likely pathogenic, VUS per ACMG/AMP guidelines) > Search first: ClinVar, ClinGen, ACMG/AMP guidelines, VarSome
• Variant type/class (missense, frameshift, nonsense, splice-site, structural)
• Allele frequency in population databases > Search first: gnomAD, 1000 Genomes, ExAC, TOPMed, dbSNP
• Somatic vs germline origin > Search first: COSMIC (somatic), ClinVar, ICGC, TCGA
• Functional consequences (loss of function, gain of function, dominant negative)
• Modifier Genes: Genes that modify disease severity or expression
• Epigenetic Information: DNA methylation, histone modifications, chromatin changes affecting disease

  Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

• Chromosomal Abnormalities: Large-scale genetic changes (aneuploidy, translocations, inversions)

  Search first: DECIPHER, ClinVar, ECARUCA, UCSC Genome Browser

5. Environmental Information

• Environmental Factors: Non-genetic contributing factors (toxins, radiation, pollution, occupational exposure)

  Search first: CTD (Comparative Toxicogenomics Database), TOXNET, PubMed, EPA databases

• Lifestyle Factors: Behavioral factors (smoking, diet, exercise, alcohol consumption)

  Search first: CDC databases, WHO, PubMed, NHANES

• Infectious Agents: If applicable, pathogens causing or triggering disease (bacteria, viruses, fungi, parasites)

  Search first: NCBI Taxonomy, ViPR, BV-BRC, MicrobeDB, GIDEON

6. Mechanism / Pathophysiology

• Molecular Pathways: Specific signaling cascades or biochemical pathways involved (Wnt, MAPK, mTOR, PI3K-AKT, etc.)

  Search first: KEGG, Reactome, WikiPathways, PathBank, BioCyc

• Cellular Processes: Cell-level mechanisms (apoptosis, autophagy, cell cycle dysregulation, inflammation, etc.)

  Search first: Gene Ontology (GO), Reactome, KEGG, PubMed

• Protein Dysfunction: How protein structure or function is altered (misfolding, aggregation, loss of function, gain of function)

  Search first: UniProt, PDB (Protein Data Bank), InterPro, Pfam, AlphaFold

• Metabolic Changes: Alterations in metabolic processes (energy metabolism, lipid metabolism, amino acid metabolism)

  Search first: KEGG, BioCyc, HMDB (Human Metabolome Database), BRENDA

• Immune System Involvement: Role of immune response (autoimmunity, immunodeficiency, chronic inflammation)

  Search first: ImmPort, Immunome Database, IEDB, Gene Ontology

• Tissue Damage Mechanisms: How tissues/ are injured (oxidative stress, ischemia, fibrosis, necrosis)

  Search first: PubMed, Gene Ontology, Reactome

• Biochemical Abnormalities: Specific molecular defects (enzyme deficiencies, receptor dysfunction, ion channel defects)

  Search first: BRENDA, UniProt, KEGG, OMIM, PubMed

• Epigenetic Changes: DNA methylation, histone modifications affecting gene expression in disease

  Search first: ENCODE, Roadmap Epigenomics, MethBase, DiseaseMeth

• Molecular Profiling (if available):
• Transcriptomics/gene expression changes > Search first: GEO (Gene Expression Omnibus), ArrayExpress, GTEx, Human Cell Atlas, SRA
• Proteomics findings > Search first: PRIDE, ProteomeXchange, Human Protein Atlas, STRING, BioGRID
• Metabolomics signatures > Search first: MetaboLights, Metabolomics Workbench, HMDB, METLIN
• Lipidomics alterations > Search first: LIPID MAPS, SwissLipids, LipidHome, Metabolomics Workbench
• Genomic structural features > Search first: UCSC Genome Browser, Ensembl, NCBI, dbVar, DGV
• Advanced Technologies (if applicable):
• Single-cell analysis findings (cell-type specific mechanisms, cellular heterogeneity) > Search first: Human Cell Atlas, Single Cell Portal, GEO, CELLxGENE
• Spatial transcriptomics findings > Search first: GEO, Spatial Research, Vizgen, 10x Genomics data
• Multi-omics integration results > Search first: TCGA, ICGC, cBioPortal, LinkedOmics, PubMed
• Functional genomics screens (CRISPR, RNAi) > Search first: DepMap, GenomeRNAi, PubMed, BioGRID ORCS

For each mechanism, describe: - The causal chain from initial trigger to clinical manifestation - Which mechanisms are upstream vs downstream - What cell types and biological processes are involved - Suggest GO terms for biological processes and CL terms for cell types

7. Anatomical Structures Affected

• Organ Level:
• Primary organs directly affected
• Secondary organ involvement (complications, secondary effects)
• Body systems involved (cardiovascular, nervous, digestive, respiratory, endocrine, etc.)

  Search first: Uberon, FMA (Foundational Model of Anatomy), OMIM, HPO, ICD-11, MeSH, SNOMED CT

• Tissue and Cell Level:
• Specific tissue types affected (epithelial, connective, muscle, nervous)
• Specific cell populations targeted (with Cell Ontology terms)

  Search first: Uberon, Human Protein Atlas, Cell Ontology, Human Cell Atlas, CellMarker, PanglaoDB

• Subcellular Level:
• Cellular compartments involved (mitochondria, nucleus, ER, lysosomes) (with GO Cellular Component terms)

  Search first: Gene Ontology (Cellular Component), UniProt, Human Protein Atlas

• Localization:
• Specific anatomical sites (with UBERON terms) > Search first: FMA, Uberon, NeuroNames (for brain), SNOMED CT
• Lateralization (unilateral, bilateral, asymmetric) > Search first: HPO, clinical literature, imaging databases

8. Temporal Development

• Onset:
• Typical age of onset (congenital, pediatric, adult, geriatric)
• Onset pattern (acute, subacute, chronic, insidious)

  Search first: OMIM, Orphanet, HPO, PubMed

• Progression:
• Disease stages (early, intermediate, advanced, end-stage) > Search first: Cancer Staging Manual (AJCC), WHO classifications, PubMed
• Progression rate (rapid, slow, variable)
• Disease course pattern (episodic, relapsing-remitting, progressive, stable)
• Disease duration (self-limited, chronic lifelong)

  Search first: Disease registries, longitudinal cohort databases, natural history studies, PubMed, Orphanet, OMIM

• Patterns:
• Remission patterns (spontaneous, treatment-induced) > Search first: Clinical trial databases, disease registries, PubMed
• Critical periods (time windows of vulnerability or opportunity for intervention) > Search first: PubMed, developmental biology databases, clinical guidelines

9. Inheritance and Population

• Epidemiology:
• Prevalence (cases per 100,000 at given time)
• Incidence (new cases per 100,000 per year)

  Search first: Orphanet, CDC, WHO, GBD (Global Burden of Disease), national registries, SEER, disease registries

• For Genetic Etiology:
• Inheritance pattern (AD, AR, X-linked, mitochondrial, multifactorial, polygenic) > Search first: OMIM, Orphanet, ClinVar, GTR (Genetic Testing Registry)
• Penetrance (complete, incomplete, age-dependent) > Search first: ClinVar, OMIM, PubMed, ClinGen
• Expressivity (variable, consistent) > Search first: OMIM, ClinVar, PubMed
• Genetic anticipation (increasing severity in successive generations) > Search first: OMIM, PubMed (especially for repeat expansion disorders)
• Germline mosaicism > Search first: ClinVar, OMIM, genetic counseling literature, PubMed
• Founder effects (population-specific mutations) > Search first: gnomAD, population genetics databases, PubMed
• Consanguinity role > Search first: OMIM, population studies, genetic counseling resources
• Carrier frequency > Search first: gnomAD, carrier screening databases, GeneReviews, GTR
• Population Demographics:
• Affected populations (ethnic or demographic groups with higher prevalence) > Search first: gnomAD, 1000 Genomes, PAGE Study, PubMed, population registries
• Geographic distribution (endemic areas, regional variation) > Search first: WHO, CDC, GBD, Orphanet, geographic epidemiology databases
• Geographic distribution of specific variants
• Sex ratio (male:female) > Search first: Disease registries, OMIM, PubMed, epidemiological databases
• Age distribution of affected individuals > Search first: CDC, disease registries, SEER, Orphanet

10. Diagnostics

• Clinical Tests:
• Laboratory tests (blood, urine, tissue chemistry, specific enzyme assays) > Search first: LOINC, LabTests Online, PubMed
• Biomarkers (proteins, metabolites, genetic markers, circulating biomarkers) > Search first: FDA Biomarker List, BEST (Biomarkers, EndpointS, and other Tools), PubMed
• Imaging studies (X-ray, CT, MRI, PET, ultrasound) > Search first: RadLex, DICOM, Radiopaedia, imaging databases
• Functional tests (pulmonary function, cardiac stress tests) > Search first: LOINC, clinical guidelines, PubMed
• Electrophysiology (EEG, EMG, ECG, nerve conduction studies) > Search first: LOINC, clinical neurophysiology databases, PubMed
• Biopsy findings (histopathology, immunohistochemistry) > Search first: SNOMED CT, College of American Pathologists resources, PubMed
• Pathology findings (microscopic examination) > Search first: SNOMED CT, Digital Pathology databases, PubMed
• Genetic Testing:

  Search first: GTR (Genetic Testing Registry), GeneReviews, ClinGen

• Overview of recommended genetic testing approach
• Whole genome sequencing (WGS) utility > Search first: GTR, ClinVar, GEL (Genomics England), gnomAD
• Whole exome sequencing (WES) utility > Search first: GTR, ClinVar, OMIM, GeneMatcher
• Gene panels (which panels, which genes) > Search first: GTR, ClinVar, laboratory-specific databases
• Single gene testing > Search first: GTR, ClinVar, OMIM, GeneReviews
• Chromosomal microarray (CMA) > Search first: DECIPHER, ClinVar, dbVar, ECARUCA
• Karyotyping > Search first: Chromosome Abnormality Database, ClinVar, cytogenetics resources
• FISH > Search first: ClinVar, cytogenetics databases, PubMed
• Mitochondrial DNA testing > Search first: MITOMAP, MSeqDR, ClinVar, GTR
• Repeat expansion testing > Search first: GTR, ClinVar, repeat expansion databases, PubMed
• Omics-Based Diagnostics (if applicable):
• RNA sequencing / transcriptomics > Search first: GEO, ArrayExpress, GTEx, RNA-seq databases
• Proteomics > Search first: PRIDE, ProteomeXchange, FDA Biomarker database
• Metabolomics > Search first: MetaboLights, Metabolomics Workbench, HMDB
• Epigenomics > Search first: GEO, ENCODE, Roadmap Epigenomics, MethBase
• Liquid biopsy > Search first: COSMIC, ClinVar, liquid biopsy databases, PubMed
• Clinical Criteria:
• Standardized diagnostic criteria (DSM, ICD, society guidelines) > Search first: DSM-5, ICD-11, clinical society guidelines, UpToDate
• Differential diagnosis (other conditions to rule out, with distinguishing features) > Search first: DynaMed, UpToDate, clinical decision support systems
• Screening:
• Screening methods for asymptomatic individuals (newborn screening, carrier screening, cascade screening) > Search first: ACMG recommendations, CDC newborn screening, GTR

11. Outcome/Prognosis

• Survival and Mortality:
• Survival rate (5-year, 10-year, overall) > Search first: SEER, cancer registries, disease-specific registries, PubMed
• Life expectancy (with and without treatment if applicable) > Search first: Orphanet, disease registries, actuarial databases, PubMed
• Mortality rate > Search first: CDC, WHO, GBD, national mortality databases
• Disease-specific mortality (deaths directly attributable to disease) > Search first: Disease registries, CDC Wonder, GBD, PubMed
• Morbidity and Function:
• Morbidity (disease-related disability and health impacts) > Search first: GBD, WHO, disability databases, PubMed
• Disability outcomes (long-term functional impairments) > Search first: ICF (International Classification of Functioning), disability registries
• Quality of life measures (EQ-5D, SF-36, PROMIS, disease-specific tools) > Search first: EQ-5D database, SF-36, PROMIS, PubMed
• Disease Course:
• Complications (secondary problems: infections, organ failure, etc.) > Search first: ICD codes, disease registries, clinical databases, PubMed
• Recovery potential (likelihood and extent of recovery, with vs without treatment) > Search first: Natural history studies, rehabilitation databases, PubMed
• Prediction:
• Prognostic factors (age, disease severity, biomarkers, treatment response) > Search first: Prognostic models databases, clinical calculators, PubMed
• Prognostic biomarkers (molecular markers predicting disease course) > Search first: FDA Biomarker database, PubMed, cancer prognostic databases

12. Treatment

• Pharmacotherapy:
• Pharmacological treatments (drug names, drug classes, mechanisms of action) > Search first: DrugBank, RxNorm, ATC classification, DailyMed, FDA databases
• Pharmacogenomics (how genetic variants affect drug metabolism, efficacy, toxicity) > Search first: PharmGKB, CPIC (Clinical Pharmacogenetics), FDA Table of PGx Biomarkers
• Advanced Therapeutics:
• Gene therapy (viral vectors, CRISPR, gene replacement, gene editing) > Search first: ClinicalTrials.gov, FDA gene therapy database, ASGCT resources
• Cell therapy (stem cell transplant, CAR-T, cellular therapeutics) > Search first: ClinicalTrials.gov, FDA cell therapy database, FACT standards
• RNA-based therapies (ASOs, siRNA, mRNA therapies) > Search first: ClinicalTrials.gov, FDA approvals, PubMed
• Targeted therapies (treatments directed at specific molecular targets) > Search first: My Cancer Genome, OncoKB, ClinicalTrials.gov, FDA approvals
• Immunotherapies (checkpoint inhibitors, monoclonal antibodies) > Search first: Cancer Immunotherapy Database, FDA approvals, ClinicalTrials.gov
• Surgical and Interventional:
• Surgical interventions (types of surgery, timing, outcomes) > Search first: CPT codes, surgical registries, clinical guidelines, PubMed
• Supportive and Rehabilitative:
• Supportive care (symptom management, pain control, nutrition) > Search first: Clinical guidelines, Cochrane Library, PubMed
• Rehabilitation (physical therapy, occupational therapy, speech therapy) > Search first: Rehabilitation medicine databases, clinical guidelines, PubMed
• Experimental:
• Experimental treatments in clinical trials (with NCT identifiers if available) > Search first: ClinicalTrials.gov, EU Clinical Trials Register, WHO ICTRP
• Treatment Outcomes:
• Treatment response rates > Search first: Clinical trial databases, FDA reviews, systematic reviews, PubMed
• Side effects and adverse events > Search first: FDA Adverse Event Reporting System (FAERS), MedWatch, PubMed
• Treatment Strategy:
• Treatment algorithms (clinical pathways, decision trees) > Search first: Clinical practice guidelines, NCCN Guidelines, UpToDate
• Combination therapies > Search first: ClinicalTrials.gov, treatment guidelines, PubMed
• Personalized medicine approaches (genotype-guided treatment) > Search first: My Cancer Genome, CIViC, PharmGKB, precision medicine databases

For each treatment, suggest NCIT (NCI Thesaurus) clinical-intervention terms where applicable.

13. Prevention

• Prevention Levels:
• Primary prevention (preventing disease occurrence: vaccination, risk factor modification) > Search first: CDC, WHO, USPSTF recommendations, Cochrane Library
• Secondary prevention (early detection and treatment: screening programs, early intervention) > Search first: USPSTF, CDC screening guidelines, WHO
• Tertiary prevention (preventing complications in those with disease) > Search first: Clinical guidelines, disease management protocols, PubMed
• Immunization: Vaccine strategies (if applicable)

  Search first: CDC vaccine schedules, WHO immunization, FDA vaccine database

• Screening and Early Detection:
• Screening programs (population-based: newborn screening, cancer screening) > Search first: CDC screening programs, USPSTF, cancer screening databases
• Genetic screening (carrier screening, preimplantation genetic diagnosis, prenatal testing) > Search first: ACMG recommendations, ACOG guidelines, GTR
• Risk stratification (identifying high-risk individuals for targeted prevention) > Search first: Risk prediction models, clinical calculators, PubMed
• Behavioral Interventions: Lifestyle modifications to reduce risk

  Search first: CDC, WHO, behavioral intervention databases, Cochrane Library

• Counseling: Genetic counseling (risk assessment, family planning guidance)

  Search first: NSGC resources, ACMG guidelines, GeneReviews

• Public Health:
• Public health interventions (sanitation, vector control, health education) > Search first: CDC, WHO, public health databases, PubMed
• Environmental interventions (reducing environmental risk factors) > Search first: EPA databases, WHO environmental health, PubMed
• Prophylaxis: Preventive medications or procedures

  Search first: Clinical guidelines, FDA approvals, PubMed

14. Other Species / Natural Disease

• Taxonomy: Species affected (with NCBI Taxon identifiers)

  Search first: NCBI Taxonomy

• Breed: Specific breeds affected (with VBO identifiers if applicable)

  Search first: VBO (Vertebrate Breed Ontology)

• Gene: Orthologous genes in other species (with NCBI Gene IDs)

  Search first: NCBI Gene

• Natural Disease:
• Naturally occurring disease in other species (companion animals, wildlife) > Search first: OMIA (Online Mendelian Inheritance in Animals), VetCompass, PubMed
• Veterinary relevance and importance in animal health > Search first: OMIA, veterinary databases, PubMed
• Comparative Biology:
• Comparative pathology (similarities and differences across species) > Search first: OMIA, comparative pathology databases, PubMed
• Evolutionary conservation of disease mechanisms > Search first: HomoloGene, OrthoMCL, Alliance of Genome Resources
• Transmission (if applicable):
• Zoonotic potential > Search first: CDC zoonotic diseases, WHO zoonoses, GIDEON
• Cross-species susceptibility > Search first: NCBI Taxonomy, veterinary databases, PubMed

15. Model Organisms

• Model Types:
• Model organism type (mammalian, invertebrate, cellular, in vitro) > Search first: Alliance of Genome Resources, model organism databases
• Specific model systems (mouse, rat, zebrafish, Drosophila, C. elegans, yeast, cell lines, organoids, iPSCs) > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, SGD, ATCC, Cellosaurus
• Induced models (drug treatment, surgical intervention, environmental manipulation) > Search first: MGI, model organism databases, PubMed
• Genetic Models:
• Types available (knockout, knock-in, transgenic, conditional, humanized) > Search first: MGI, IMPC, KOMP, EuMMCR, IMSR
• Model Characteristics:
• Phenotype recapitulation (how well model reproduces human disease features) > Search first: Model organism databases, comparative studies, PubMed
• Model limitations (aspects of human disease not captured) > Search first: Model organism databases, PubMed, review articles
• Applications:
• Research applications (what aspects of disease can be studied) > Search first: Model organism databases, PubMed
• Resources:
• Model databases > Search first: MGI, RGD, ZFIN, FlyBase, WormBase, IMSR, EMMA, MMRRC

Citation Requirements

• Cite primary literature (PMID preferred) for all mechanistic and clinical claims
• Prioritize recent reviews and landmark papers
• Include direct quotes from abstracts where possible to support key statements
• Distinguish evidence source types: human clinical, model organism, in vitro, computational

Output Format

Structure your response as a comprehensive narrative organized by the sections above. For each section, provide: - Factual content with specific details (numbers, percentages, gene names, variant nomenclature) - Ontology term suggestions (HPO, GO, CL, UBERON, CHEBI, NCIT, MONDO) where applicable - Evidence citations with PMIDs - Direct quotes from abstracts to support key claims - Clear indication when information is not available or not applicable for this disease

This report will be used to populate a disease knowledge base entry with: - Pathophysiology descriptions with causal chains - Gene/protein annotations (HGNC, GO terms) - Phenotype associations (HP terms) with frequencies - Cell type involvement (CL terms) - Anatomical locations (UBERON terms) - Chemical entities (CHEBI terms) - Treatment annotations (NCIT terms) - Evidence items with PMIDs and exact abstract quotes - Epidemiology, prognosis, diagnostic, and prevention information - Animal model descriptions with phenotype recapitulation details

Vein of Galen aneurysmal malformation: disease-characteristics report

Executive summary

Vein of Galen aneurysmal malformation (VGAM; increasingly VOGM, “vein of Galen malformation”) is a congenital, high-flow cerebral arteriovenous shunt. Primitive choroidal/subependymal arteries connect directly to the persistent median prosencephalic vein of Markowski, without an intervening capillary bed. It is therefore neither a true aneurysm nor usually a lesion of the mature vein of Galen. The resulting low-resistance circuit can produce fetal or neonatal high-output heart failure, pulmonary hypertension, systemic and cerebral steal, venous hypertension, hydrocephalus, and irreversible brain injury. True VOGM must be separated from a pial AV fistula or AVM that secondarily drains into an enlarged vein of Galen because anatomy, genetics, and treatment risk differ. (tas2022arteriovenouscerebralhigh pages 4-5, tas2022arteriovenouscerebralhigh pages 2-3, zhao2023mutationofkey pages 1-2)

The most important recent advance is the 2023 demonstration that VOGM is partly a disorder of developing endothelial Ras-regulatory networks. Analysis of 310 proband-family exomes and 336,326 cerebrovascular single-cell transcriptomes implicated RASA1, EPHB4, ACVRL1, NOTCH1, ITGB1, and PTPN11 and localized susceptibility to fetal endothelial cells. Endovascular embolization remains standard treatment; fetal embolization is investigational. (zhao2023mutationofkey pages 7-8, zhao2023mutationofkey pages 1-2, zhao2023mutationofkey pages 13-14)

Table: This table summarizes the strongest currently available evidence for vein of Galen aneurysmal malformation across definition, epidemiology, clinical features, genetics, mechanisms, diagnosis, treatment, prognosis, prevention, and models. It is designed as a concise knowledge-base matrix that distinguishes established findings from current evidence gaps.

1. Disease information

Definition and terminology

Preferred terms are vein of Galen aneurysmal malformation, vein of Galen malformation, VGAM, and VOGM. Other names include aneurysmal malformation of the vein of Galen, Galenic arteriovenous malformation, and median prosencephalic arteriovenous fistula. “Vein of Galen aneurysm” is clinically common but anatomically misleading.

A genuine VOGM drains into the embryonic median prosencephalic vein, which drains the shunt while normal deep cerebral venous blood is rerouted through alternative channels. It should not be conflated with “vein of Galen aneurysmal dilatation,” in which another AVM/AVF drains into the mature Galenic system. (tas2022arteriovenouscerebralhigh pages 4-5, tas2022arteriovenouscerebralhigh pages 2-3, vivanti2018lossoffunction pages 1-2)

Identifiers

• MONDO: a stable disease-specific MONDO identifier could not be verified from the retrieved primary literature; validate directly against the current MONDO release before ingestion.
• OMIM: no single, universally accepted disease-specific OMIM entry was established in the retrieved evidence. Relevant Mendelian disorders include RASA1/EPHB4-related capillary malformation–AVM and ACVRL1/ENG-related hereditary hemorrhagic telangiectasia.
• MeSH: generally indexed under Arteriovenous Malformations and related cerebral vascular-malformation terms rather than a unique VGAM descriptor.
• ICD-10/ICD-11: no uniquely specific code was verified; cases are generally coded under congenital cerebral/circulatory-system vascular malformations. Local coding rules should be checked.
• Orphanet: a disease-specific number was not independently verified in the retrieved evidence.

The evidence summarized here is aggregated disease-level evidence from family exomes, clinical cohorts, single-cell atlases, functional studies, and trial registries—not individual EHR-derived data.

2. Etiology, risk, and protective factors

VOGM originates during embryonic cerebrovascular development, approximately gestational weeks 6–11. Persistence of abnormal primitive arteriovenous connections prevents normal capillary and arterial–venous hierarchy formation. (singh2022recurrentveinof pages 1-2, zhao2023mutationofkey pages 1-2)

Genetic factors

The disease is usually apparently sporadic, but rare damaging germline variants explain an important subset. In a 115-child high-flow-shunt cohort, variants were found in 39% overall; RASA1, EPHB4, and HHT-associated genes represented 25%, 8%, and 5%, respectively. Those percentages describe that mixed referral cohort and should not be treated as population-wide VOGM frequencies. (tas2022arteriovenouscerebralhigh pages 2-3, tas2022arteriovenouscerebralhigh pages 1-2)

Established or strongly supported genes are RASA1 and EPHB4; additional evidence implicates ACVRL1, NOTCH1, ITGB1, and PTPN11. Rare ENG/SMAD4-associated presentations have been reported, but some may represent phenotypically related cerebral AV shunts rather than anatomically genuine VOGM. (singh2022recurrentveinof pages 1-2, zhao2023mutationofkey pages 7-8, zhao2023mutationofkey pages 1-2)

Environmental, infectious, and lifestyle factors

No reproducible maternal toxin, infection, medication, diet, smoking, alcohol, occupational exposure, or lifestyle risk factor is established. No protective genetic allele, diet, medication, or behavior is validated. The malformation is congenital and developmental, not infectious or contagious. Consequently, evidence for gene–environment interaction is presently insufficient.

3. Phenotypes

Presentation varies with shunt flow, venous restriction, brain injury, and age.

• Fetal: cardiomegaly, tricuspid regurgitation, hydrops, enlarged neck vessels, and abnormal intracranial flow; severe antenatal cardiac failure is an adverse sign. Detection is usually in the late second or third trimester. Suggested HPO labels: fetal cardiomegaly, hydrops fetalis, arteriovenous malformation, abnormal fetal ultrasonography. (singh2022recurrentveinof pages 1-2)
• Neonatal: high-output congestive heart failure, pulmonary hypertension, respiratory distress, hypotension/systemic hypoperfusion, multiorgan dysfunction, and encephalopathy. Severity ranges from compensated to rapidly fatal. Suggested HPO: high-output cardiac failure, pulmonary hypertension, respiratory distress, hypotension, encephalopathy. (singh2022recurrentveinof pages 1-2, zhao2023mutationofkey pages 1-2)
• Infant/child: macrocephaly, hydrocephalus, prominent scalp veins, seizures, developmental delay, focal neurologic deficit, and failure to thrive. These may evolve progressively through venous hypertension or prior ischemic/hemorrhagic injury. Suggested HPO: hydrocephalus, macrocephaly, seizure, global developmental delay, abnormality of cerebral veins. (singh2022recurrentveinof pages 1-2, zhao2023mutationofkey pages 1-2)
• Older child/adult: uncommon; headache, seizures, hemorrhage, hydrocephalus, cognitive difficulty, or incidental detection may occur.

In the 115-child mixed cerebral high-flow-shunt cohort, 62% had a good and 38% a poor outcome at a median 27-month survivor follow-up. This is not a phenotype-frequency survey of unselected VOGM. (tas2022arteriovenouscerebralhigh pages 2-3)

Quality-of-life effects can include motor, language, cognitive, educational, and caregiver burdens. Disease-specific validated patient-reported outcome data are sparse; formal long-term neuropsychological follow-up is preferable to survival or gross motor status alone.

4. Genetic and molecular information

RASA1

RASA1 encodes p120 RasGAP, a negative regulator of RAS. In the 2023 study, de novo loss-of-function variants showed 2,042.5-fold enrichment (p=4.79×10⁻⁷); case-control enrichment versus gnomAD had OR 67.5 (p=2.20×10⁻⁸). Reported protein variants include p.Arg427, p.Val527Mfs16, p.Arg709, p.Tyr872, and p.His743Thrfs*24. These are germline nonsense/frameshift variants expected to cause loss of function, often through nonsense-mediated decay and excessive Ras/ERK/MAPK activity. (zhao2023geneticdysregulationof pages 6-8, zhao2023geneticdysregulationof pages 30-35)

EPHB4

EPHB4 encodes a venous endothelial receptor tyrosine kinase. Rare damaging transmitted variants were enriched 17.5-fold (p=1.22×10⁻⁵). Examples include p.Lys650Asn, p.Arg838Trp, and p.Phe867Leu. Functional assays found preserved protein stability but reduced or absent phosphotyrosine signal, supporting impaired kinase function. EPHB4 variants appeared specific to genuine VOGM in one comparative cohort. (tas2022arteriovenouscerebralhigh pages 1-2, zhao2023mutationofkey pages 1-2, zhao2023geneticdysregulationof pages 30-35, zhao2023mutationofkey pages 5-7)

Additional genes

• ACVRL1/ALK1: reported p.Cys344Tyr and p.Arg484Gln kinase-domain variants; multigenerational segregation and zebrafish rescue experiments support pathogenicity.
• PTPN11/SHP2: p.Tyr63Cys is an example; activating PTPN11 variation can increase RAS signaling.
• NOTCH1 and ITGB1: rare damaging variants implicate arterial specification and focal-adhesion/PI3K-AKT biology, but evidence is less mature than for RASA1/EPHB4. (zhao2023mutationofkey pages 7-8, zhao2023mutationofkey pages 1-2, zhao2023mutationofkey pages 13-14, zhao2023geneticdysregulationof pages 30-35)

Variants are usually heterozygous germline, de novo or inherited. Inherited disease behaves as autosomal dominant with incomplete penetrance and variable expressivity; relatives may have capillary malformations, other AVMs, or no detected VOGM. A local postzygotic “second hit” is biologically plausible and supported by model data, but direct demonstration in human VOGM tissue remains limited. Population allele frequencies must be retrieved variant-by-variant from the current gnomAD release; no meaningful carrier frequency exists for VOGM as a whole. (zhao2023geneticdysregulationof pages 12-14, duran2019mutationsinchromatin pages 1-3, zhao2023mutationofkey pages 5-7)

No recurrent chromosomal abnormality, repeat expansion, mitochondrial variant, epigenetic signature, or validated modifier gene is established. Chromatin-modifier de novo variants were enriched in an earlier 55-proband study, but a clinically actionable epigenetic classification has not emerged. (duran2019mutationsinchromatin pages 1-3)

5. Environmental information

No validated environmental, lifestyle, or infectious cause is known. VOGM is not attributable to postnatal behavior, and there is no evidence that diet or exercise changes occurrence. Maternal exposures should therefore not be represented as causal without case-specific evidence. CTD/toxicogenomic associations would be hypothesis-generating rather than disease-defining.

6. Mechanism and pathophysiology

Causal chain

1. Upstream developmental susceptibility: damaging variants disturb EPHB4–RASA1, ACVRL1/TGF-β-BMP, NOTCH, integrin/focal-adhesion, or PTPN11-RAS signaling in fetal endothelial cells.
2. Arteriovenous specification failure: endothelial identity, angiogenic sprouting, remodeling, and arterial-capillary-venous hierarchy formation are impaired.
3. Anatomic lesion: primitive choroidal arteries retain direct connections to the median prosencephalic vein.
4. Hemodynamic amplification: the low-resistance shunt causes extreme venous flow/pressure and arterial steal.
5. Downstream organ injury: high cardiac preload produces high-output failure and pulmonary hypertension; systemic steal causes renal/hepatic/gut hypoperfusion; cerebral venous hypertension and reduced effective perfusion cause edema, hydrocephalus, ischemia, calcification, atrophy, or hemorrhage. (zhao2023mutationofkey pages 1-2, zhao2023geneticdysregulationof pages 12-14)

The 2023 integrated analysis found endothelial-cell enrichment (p=6.43×10⁻⁶), 11.4-fold enrichment for positive regulation of vascular development (p=7.95×10⁻⁸), and involvement of focal-adhesion–PI3K–AKT–mTOR pathways. Its abstract states: “Integrative genomic analysis defined developing endothelial cells as a likely spatio-temporal locus of VOGM pathophysiology.” (zhao2023mutationofkey pages 7-8, zhao2023mutationofkey pages 1-2)

Suggested GO biological-process labels include blood-vessel development, angiogenesis, artery morphogenesis, vein morphogenesis, endothelial-cell differentiation, RAS protein signal transduction, ERK1/ERK2 cascade, and regulation of vascular permeability. Suggested CL labels are endothelial cell, vascular endothelial cell, arterial endothelial cell, and venous endothelial cell. These labels should be mapped to the current ontology release before ingestion.

Single-cell transcriptomics is currently the strongest molecular-profiling evidence. Disease-specific proteomic, metabolomic, lipidomic, spatial-transcriptomic, and validated circulating biomarker signatures are not established. No VOGM-specific CRISPR screen or patient-organoid platform is yet standard.

7. Anatomical structures affected

The primary lesion occupies the midline deep cerebral venous compartment, involving the median prosencephalic vein, primitive choroidal/subependymal arterial feeders, falcine/straight sinus outflow, and associated dural sinuses. Normal deep veins may use alternative drainage. The lesion is midline rather than meaningfully unilateral. (tas2022arteriovenouscerebralhigh pages 4-5, vivanti2018lossoffunction pages 1-2, zhao2023mutationofkey pages 1-2)

Secondary structures include cerebral white matter and cortex, ventricles, heart, pulmonary vasculature, and—through systemic steal—the kidneys, liver, and gastrointestinal tract. Relevant tissue is vascular endothelium and vessel wall; the principal subcellular components are the plasma membrane receptor-signaling complex and cytoplasmic RAS/MAPK machinery.

Suggested UBERON labels: brain, cerebral blood vessel, cerebral vein, diencephalon, ventricular system of brain, heart, and pulmonary artery. Exact identifiers require current-release validation. Suggested GO cellular-component labels include plasma membrane, receptor complex, and cytoplasm.

8. Temporal development

The lesion forms prenatally, classically during weeks 6–11, but may not become sonographically conspicuous until late gestation. Clinical course is driven by physiology rather than a formal stage system. (singh2022recurrentveinof pages 1-2)

A practical sequence is: fetal compensated shunt → fetal cardiac strain/hydrops in severe disease → abrupt neonatal decompensation as placental resistance disappears → later compensated infancy with hydrocephalus or neurodevelopmental sequelae. Untreated severe neonatal disease can progress rapidly; treated disease remains chronic until durable shunt closure and surveillance are achieved. Spontaneous thrombosis is reported but is unpredictable and not a prevention strategy.

The principal therapeutic window is before irreversible brain or multiorgan injury. Stable infants are often allowed to grow before staged embolization; refractory neonatal failure demands earlier intervention. Experimental fetal treatment targets selected late-gestation fetuses expected to decompensate after birth. (NCT07483255 chunk 1, NCT04434729 chunk 1)

9. Inheritance and population

Published incidence estimates vary from approximately 1 in 25,000 to 1 in 50,000 births. One source reports a male:female ratio near 3:1 and approximately 30% of pediatric vascular malformations, but referral and definitional differences limit generalization. No well-established ethnic or endemic geographic concentration exists. (singh2022recurrentveinof pages 1-2, vivanti2018lossoffunction pages 1-2)

Most cases remain isolated. Mendelian cases are generally autosomal dominant with incomplete penetrance and variable expressivity. Anticipation, founder effects, consanguinity dependence, carrier frequency, and germline mosaicism have not been established. A report of recurrent severe fetal disease in a consanguineous family with parental ENG p.Asp264Asn proposed biallelic fetal disease, but fetal DNA was unavailable; this remains a case-level hypothesis rather than a general inheritance model. (singh2022recurrentveinof pages 1-2)

10. Diagnostics

Imaging and physiological assessment

• Prenatal Doppler ultrasound: midline cystic-appearing structure with turbulent high-velocity flow; assesses cardiomegaly, hydrops, and umbilical/cerebral hemodynamics.
• Fetal MRI: confirms anatomy, falcine/straight sinus dimensions, venous outflow, and pre-existing ischemic, hemorrhagic, or atrophic brain injury.
• Postnatal cranial Doppler and echocardiography: quantify shunt physiology, ventricular function, pulmonary hypertension, systemic steal, and venous congestion.
• MRI/MRA/MRV: define brain integrity, arterial supply, venous drainage, hydrocephalus, and treatment planning.
• Catheter digital-subtraction angiography: definitive angioarchitecture and procedural roadmap; generally performed when intervention is intended.
• CT: useful in emergencies for hemorrhage/calcification but avoided when MRI/ultrasound suffice because of radiation.

No diagnostic blood biomarker, enzyme assay, biopsy, histopathologic criterion, EEG signature, or newborn-screening analyte exists. ECG, blood gases, lactate, renal/hepatic tests, BNP/troponin, and EEG are supportive measures of organ injury, not disease-specific diagnostics.

Clinical triage and differential diagnosis

Multidisciplinary teams integrate cardiac, cerebral, respiratory, hepatic, and renal status—often using the Bicêtre neonatal evaluation score—to distinguish candidates for stabilization/delayed treatment, urgent embolization, or palliation where irreversible brain injury makes intervention futile. Exact cutoffs should be taken from the institution’s validated protocol rather than reconstructed from secondary summaries.

Differentials include arachnoid cyst, porencephalic cyst, Dandy–Walker-spectrum lesion, dural sinus malformation, pial AVF, cerebral AVM draining into the Galenic system, and other causes of neonatal high-output failure. Demonstration of internal blood flow separates VOGM from a simple cyst.

Genetic testing

Testing is reasonable when there are capillary malformations, telangiectases, multiple AVMs, family history, recurrent fetal disease, or syndromic findings. A vascular-malformation panel should include RASA1, EPHB4, ACVRL1, ENG, SMAD4, GDF2, NOTCH1, ITGB1, and PTPN11, with phenotype-directed interpretation. Trio WES/WGS is appropriate for unexplained disease and improves de novo-variant detection; the largest study explicitly demonstrates WES utility. CMA/karyotype is reserved for additional congenital anomalies and is not a primary VOGM test. FISH, mtDNA, and repeat-expansion tests have no routine role. A negative blood test does not exclude low-level lesion-restricted mosaicism. (zhao2023mutationofkey pages 1-2, zhao2023mutationofkey pages 13-14)

11. Outcome and prognosis

Adverse prognostic factors include antenatal hydrops/cardiac failure, severe neonatal multiorgan dysfunction, extensive pre-treatment brain injury, uncontrolled pulmonary hypertension, restrictive venous outflow, and ischemic/hemorrhagic procedural complications. Favorable factors include preserved brain parenchyma, successful physiologic stabilization, and staged flow reduction at an expert center.

Historical untreated severe infantile disease was described as nearly uniformly fatal; this should not be used as a modern treated mortality estimate. One recent source summarized approximately 80% mortality with antenatal cardiac failure. In the mixed 115-child cohort, 62% had a good outcome and 38% a poor outcome. Contemporary center-specific survival is better, but no defensible universal 5- or 10-year survival percentage was available in the retrieved evidence. (singh2022recurrentveinof pages 1-2, tas2022arteriovenouscerebralhigh pages 2-3, tas2022arteriovenouscerebralhigh pages 1-2)

Survivors may have normal development or persistent epilepsy, motor impairment, cerebral palsy, language/cognitive deficits, behavioral/educational difficulty, hydrocephalus, or visual impairment. Long-term Bayley/Vineland-type testing is more informative than discharge neurological examination. Disease-specific EQ-5D/SF-36 norms and validated molecular prognostic biomarkers are unavailable.

12. Treatment

Standard strategy

Staged endovascular embolization is standard disease-modifying therapy. A transarterial approach commonly uses n-butyl cyanoacrylate or another liquid embolic to occlude selected fistulous connections progressively while avoiding abrupt venous thrombosis and perfusion shifts. Transvenous coil techniques may be used in selected anatomy or as a final curative procedure at specialized centers. Open surgery and radiosurgery have little routine role because of deep location, high flow, and treatment latency. Improved antenatal detection and endovascular treatment have improved prognosis. (vivanti2018lossoffunction pages 1-2, tas2022arteriovenouscerebralhigh pages 1-2)

A practical algorithm is:

1. Deliver at a tertiary fetal/neonatal cardiac and neurointerventional center.
2. Stabilize ventilation, pulmonary pressure, perfusion, and heart failure.
3. Image brain and angioarchitecture; assess reversibility of organ injury.
4. If stable, defer/stage embolization to permit growth; if refractory failure persists, perform urgent partial flow reduction.
5. Repeat staged embolization until physiological control or angiographic cure; continue cardiac, imaging, and neurodevelopmental surveillance.

Supportive treatment includes cautious ventilation, inotropes/vasoactive therapy, diuretics when appropriate, pulmonary-hypertension management, nutrition, seizure treatment, and physical/occupational/speech therapy. Drugs do not close the malformation. There is no validated pharmacogenomic, gene, cell, RNA, immunologic, or RAS-targeted therapy for VOGM.

Important embolization complications include cerebral ischemia, hemorrhage, venous thrombosis, non-target embolization, vessel perforation, contrast/radiation exposure, and acute hemodynamic instability. NCIT label suggestions include Endovascular Embolization, Transarterial Embolization, Coil Embolization, Magnetic Resonance Imaging, Ultrasonography, Physical Therapy, Occupational Therapy, and Speech Therapy; exact NCIT codes require release validation.

Experimental fetal treatment

NCT04434729 enrolled seven pregnancies in a prospective single-arm study using maternal transuterine, fetal transcranial torcular puncture and coil embolization of the median prosencephalic vein. Eligibility included preserved brain parenchyma and a straight/falcine sinus ≥7 mm; outcomes included fetal safety, neonatal death, urgent neonatal embolization, brain injury, and two-year neurodevelopment. ClinicalTrials.gov, registered study information retrieved as 2022. (NCT04434729 chunk 1)

NCT07483255 is a planned/recruiting Phase II study of 20 pregnancies using a related technique at ≥34 weeks, with 30-day mortality and 24-month safety/neurodevelopmental outcomes. Its registry start is 2026, so it is a future/current-development item rather than 2023–2024 evidence. ClinicalTrials.gov. (NCT07483255 chunk 1)

13. Prevention

There is no established primary prevention, vaccine, prophylactic drug, or lifestyle intervention. Secondary prevention consists of prenatal detection, referral before delivery, planned delivery at an expert center, and rapid postnatal assessment. Tertiary prevention includes timely embolization before irreversible injury, management of heart failure/pulmonary hypertension, seizure control, rehabilitation, and developmental surveillance.

For a pathogenic familial variant, genetic counseling should explain autosomal-dominant transmission but incomplete penetrance and unpredictable expression. Targeted prenatal or preimplantation testing can establish fetal genotype but cannot reliably predict whether or how severely VOGM will develop. Serial targeted fetal ultrasound/MRI is therefore relevant in known RASA1/EPHB4/HHT families. (vivanti2018lossoffunction pages 1-2, zhao2023mutationofkey pages 13-14, zhao2023mutationofkey pages 5-7)

14. Other species and natural disease

No reproducible naturally occurring homologous VGAM syndrome was identified in companion animals, livestock, or wildlife. There is no zoonotic potential or transmission. Orthologues of RASA1, EPHB4, ACVRL1, NOTCH1, ITGB1, and PTPN11 are evolutionarily conserved, but database-specific NCBI Gene and VBO identifiers should be populated directly from NCBI/Alliance releases rather than inferred from the human literature.

15. Model organisms

• Mouse: endothelial conditional expression of VOGM-associated EPHB4 p.Phe867Leu, particularly with a second-hit allele, impaired fetal angiogenesis, vascular-plexus remodeling, VEGF-regulated sprouting, and hierarchical arterial-capillary-venous development. It models developmental mechanism better than the full human cardiocerebral syndrome. (zhao2023mutationofkey pages 1-2, zhao2023mutationofkey pages 13-14)
• Zebrafish: acvrl1a/b depletion caused enlarged vessels and supernumerary AV connections/VOGM-like venous dilation; wild-type but not mutant ACVRL1 mRNA rescued the phenotype. Advantages are live vascular imaging and rapid functional testing; limitations include species-specific cerebral venous anatomy and hemodynamics. (zhao2023mutationofkey pages 7-8, zhao2023geneticdysregulationof pages 30-35)
• Cellular assays: COS-7 transfection, cycloheximide chase, immunoblotting, and phosphotyrosine assays showed that EPHB4 domain-missense variants can preserve stability while impairing kinase activity. These assays establish protein dysfunction but do not reproduce organ-level shunting. (zhao2023mutationofkey pages 5-7)

Key recent source and evidence notes

The principal 2023 primary paper is Zhao et al., “Mutation of key signaling regulators of cerebrovascular development in vein of Galen malformations,” Nature Communications, published November 2023, DOI 10.1038/s41467-023-43062-z. Its abstract reports: “We found the Ras suppressor p120 RasGAP (RASA1) harbored a genome-wide significant burden of loss-of-function de novo variants,” and that developing endothelial cells were the likely spatiotemporal locus. (zhao2023mutationofkey pages 1-2)

Other key sources are Tas et al., Frontiers in Pediatrics, April 2022, DOI 10.3389/fped.2022.871565; Vivanti et al., Brain, April 2018, DOI 10.1093/brain/awy020; and Duran et al., Neuron, February 2019, DOI 10.1016/j.neuron.2018.11.041. (tas2022arteriovenouscerebralhigh pages 2-3, vivanti2018lossoffunction pages 1-2, duran2019mutationsinchromatin pages 1-3)

PMIDs were not exposed in the retrieved records and therefore are not guessed. The most important evidence gaps are contemporary population epidemiology, standardized long-term quality-of-life data, lesion-tissue somatic sequencing, validated prognostic biomarkers, disease-specific multi-omics, and controlled evidence for fetal intervention.

References

1. (tas2022arteriovenouscerebralhigh pages 4-5): Berivan Tas, Daniele Starnoni, Stanislas Smajda, Alexandre J. Vivanti, Catherine Adamsbaum, Mélanie Eyries, Judith Melki, Marcel Tawk, Augustin Ozanne, Nicole Revencu, Florent Soubrier, Selima Siala, Miikka Vikkula, Kumaran Deiva, and Guillaume Saliou. Arteriovenous cerebral high flow shunts in children: from genotype to phenotype. Frontiers in Pediatrics, Apr 2022. URL: https://doi.org/10.3389/fped.2022.871565, doi:10.3389/fped.2022.871565. This article has 13 citations.

2. (tas2022arteriovenouscerebralhigh pages 2-3): Berivan Tas, Daniele Starnoni, Stanislas Smajda, Alexandre J. Vivanti, Catherine Adamsbaum, Mélanie Eyries, Judith Melki, Marcel Tawk, Augustin Ozanne, Nicole Revencu, Florent Soubrier, Selima Siala, Miikka Vikkula, Kumaran Deiva, and Guillaume Saliou. Arteriovenous cerebral high flow shunts in children: from genotype to phenotype. Frontiers in Pediatrics, Apr 2022. URL: https://doi.org/10.3389/fped.2022.871565, doi:10.3389/fped.2022.871565. This article has 13 citations.

3. (zhao2023mutationofkey pages 1-2): Shujuan Zhao, Kedous Y. Mekbib, Martijn A. van der Ent, Garrett Allington, Andrew Prendergast, Jocelyn E. Chau, Hannah Smith, John Shohfi, Jack Ocken, Daniel Duran, Charuta G. Furey, Le Thi Hao, Phan Q. Duy, Benjamin C. Reeves, Junhui Zhang, Carol Nelson-Williams, Di Chen, Boyang Li, Timothy Nottoli, Suxia Bai, Myron Rolle, Xue Zeng, Weilai Dong, Po-Ying Fu, Yung-Chun Wang, Shrikant Mane, Paulina Piwowarczyk, Katie Pricola Fehnel, Alfred Pokmeng See, Bermans J. Iskandar, Beverly Aagaard-Kienitz, Quentin J. Moyer, Evan Dennis, Emre Kiziltug, Adam J. Kundishora, Tyrone DeSpenza, Ana B. W. Greenberg, Seblewengel M. Kidanemariam, Andrew T. Hale, James M. Johnston, Eric M. Jackson, Phillip B. Storm, Shih-Shan Lang, William E. Butler, Bob S. Carter, Paul Chapman, Christopher J. Stapleton, Aman B. Patel, Georges Rodesch, Stanislas Smajda, Alejandro Berenstein, Tanyeri Barak, E. Zeynep Erson-Omay, Hongyu Zhao, Andres Moreno-De-Luca, Mark R. Proctor, Edward R. Smith, Darren B. Orbach, Seth L. Alper, Stefania Nicoli, Titus J. Boggon, Richard P. Lifton, Murat Gunel, Philip D. King, Sheng Chih Jin, and Kristopher T. Kahle. Mutation of key signaling regulators of cerebrovascular development in vein of galen malformations. Nature Communications, Nov 2023. URL: https://doi.org/10.1038/s41467-023-43062-z, doi:10.1038/s41467-023-43062-z. This article has 32 citations and is from a highest quality peer-reviewed journal.

4. (zhao2023mutationofkey pages 7-8): Shujuan Zhao, Kedous Y. Mekbib, Martijn A. van der Ent, Garrett Allington, Andrew Prendergast, Jocelyn E. Chau, Hannah Smith, John Shohfi, Jack Ocken, Daniel Duran, Charuta G. Furey, Le Thi Hao, Phan Q. Duy, Benjamin C. Reeves, Junhui Zhang, Carol Nelson-Williams, Di Chen, Boyang Li, Timothy Nottoli, Suxia Bai, Myron Rolle, Xue Zeng, Weilai Dong, Po-Ying Fu, Yung-Chun Wang, Shrikant Mane, Paulina Piwowarczyk, Katie Pricola Fehnel, Alfred Pokmeng See, Bermans J. Iskandar, Beverly Aagaard-Kienitz, Quentin J. Moyer, Evan Dennis, Emre Kiziltug, Adam J. Kundishora, Tyrone DeSpenza, Ana B. W. Greenberg, Seblewengel M. Kidanemariam, Andrew T. Hale, James M. Johnston, Eric M. Jackson, Phillip B. Storm, Shih-Shan Lang, William E. Butler, Bob S. Carter, Paul Chapman, Christopher J. Stapleton, Aman B. Patel, Georges Rodesch, Stanislas Smajda, Alejandro Berenstein, Tanyeri Barak, E. Zeynep Erson-Omay, Hongyu Zhao, Andres Moreno-De-Luca, Mark R. Proctor, Edward R. Smith, Darren B. Orbach, Seth L. Alper, Stefania Nicoli, Titus J. Boggon, Richard P. Lifton, Murat Gunel, Philip D. King, Sheng Chih Jin, and Kristopher T. Kahle. Mutation of key signaling regulators of cerebrovascular development in vein of galen malformations. Nature Communications, Nov 2023. URL: https://doi.org/10.1038/s41467-023-43062-z, doi:10.1038/s41467-023-43062-z. This article has 32 citations and is from a highest quality peer-reviewed journal.

5. (zhao2023mutationofkey pages 13-14): Shujuan Zhao, Kedous Y. Mekbib, Martijn A. van der Ent, Garrett Allington, Andrew Prendergast, Jocelyn E. Chau, Hannah Smith, John Shohfi, Jack Ocken, Daniel Duran, Charuta G. Furey, Le Thi Hao, Phan Q. Duy, Benjamin C. Reeves, Junhui Zhang, Carol Nelson-Williams, Di Chen, Boyang Li, Timothy Nottoli, Suxia Bai, Myron Rolle, Xue Zeng, Weilai Dong, Po-Ying Fu, Yung-Chun Wang, Shrikant Mane, Paulina Piwowarczyk, Katie Pricola Fehnel, Alfred Pokmeng See, Bermans J. Iskandar, Beverly Aagaard-Kienitz, Quentin J. Moyer, Evan Dennis, Emre Kiziltug, Adam J. Kundishora, Tyrone DeSpenza, Ana B. W. Greenberg, Seblewengel M. Kidanemariam, Andrew T. Hale, James M. Johnston, Eric M. Jackson, Phillip B. Storm, Shih-Shan Lang, William E. Butler, Bob S. Carter, Paul Chapman, Christopher J. Stapleton, Aman B. Patel, Georges Rodesch, Stanislas Smajda, Alejandro Berenstein, Tanyeri Barak, E. Zeynep Erson-Omay, Hongyu Zhao, Andres Moreno-De-Luca, Mark R. Proctor, Edward R. Smith, Darren B. Orbach, Seth L. Alper, Stefania Nicoli, Titus J. Boggon, Richard P. Lifton, Murat Gunel, Philip D. King, Sheng Chih Jin, and Kristopher T. Kahle. Mutation of key signaling regulators of cerebrovascular development in vein of galen malformations. Nature Communications, Nov 2023. URL: https://doi.org/10.1038/s41467-023-43062-z, doi:10.1038/s41467-023-43062-z. This article has 32 citations and is from a highest quality peer-reviewed journal.

6. (singh2022recurrentveinof pages 1-2): Arati Singh, Neelam Saini, Geetanjli Behl, Shagun Aggarwal, and Geeta Kolar. Recurrent vein of galen aneurysmal malformation as a presentation of hereditary hemorrhagic telangiectasia. Molecular Syndromology, 13:440-446, Apr 2022. URL: https://doi.org/10.1159/000522352, doi:10.1159/000522352. This article has 5 citations and is from a peer-reviewed journal.

7. (vivanti2018lossoffunction pages 1-2): Alexandre Vivanti, Augustin Ozanne, Cynthia Grondin, Guillaume Saliou, Loic Quevarec, Helène Maurey, Patrick Aubourg, Alexandra Benachi, Marta Gut, Ivo Gut, Jelena Martinovic, Marie Victoire Sénat, Marcel Tawk, and Judith Melki. Loss of function mutations in ephb4 are responsible for vein of galen aneurysmal malformation. Brain, 141:979–988, Apr 2018. URL: https://doi.org/10.1093/brain/awy020, doi:10.1093/brain/awy020. This article has 75 citations and is from a highest quality peer-reviewed journal.

8. (tas2022arteriovenouscerebralhigh pages 1-2): Berivan Tas, Daniele Starnoni, Stanislas Smajda, Alexandre J. Vivanti, Catherine Adamsbaum, Mélanie Eyries, Judith Melki, Marcel Tawk, Augustin Ozanne, Nicole Revencu, Florent Soubrier, Selima Siala, Miikka Vikkula, Kumaran Deiva, and Guillaume Saliou. Arteriovenous cerebral high flow shunts in children: from genotype to phenotype. Frontiers in Pediatrics, Apr 2022. URL: https://doi.org/10.3389/fped.2022.871565, doi:10.3389/fped.2022.871565. This article has 13 citations.

9. (zhao2023geneticdysregulationof pages 6-8): Shujuan Zhao, Kedous Y. Mekbib, Martijn A. van der Ent, Garrett Allington, Andrew Prendergast, Jocelyn E. Chau, Hannah Smith, John Shohfi, Jack Ocken, Daniel Duran, Charuta G. Furey, Hao Thi Le, Phan Q. Duy, Benjamin C. Reeves, Junhui Zhang, Carol Nelson-Williams, Di Chen, Boyang Li, Timothy Nottoli, Suxia Bai, Myron Rolle, Xue Zeng, Weilai Dong, Po-Ying Fu, Yung-Chun Wang, Shrikant Mane, Paulina Piwowarczyk, Katie Pricola Fehnel, Alfred Pokmeng See, Bermans J. Iskandar, Beverly Aagaard-Kienitz, Adam J. Kundishora, Tyrone DeSpenza, Ana B.W. Greenberg, Seblewengel M. Kidanemariam, Andrew T. Hale, James M. Johnston, Eric M. Jackson, Phillip B. Storm, Shih-Shan Lang, William E. Butler, Bob S. Carter, Paul Chapman, Christopher J. Stapleton, Aman B. Patel, Georges Rodesch, Stanislas Smajda, Alejandro Berenstein, Tanyeri Barak, E. Zeynep Erson-Omay, Hongyu Zhao, Andres Moreno-De-Luca, Mark R. Proctor, Edward R. Smith, Darren B. Orbach, Seth L. Alper, Stefania Nicoli, Titus J. Boggon, Richard P. Lifton, Murat Gunel, Philip D. King, Sheng Chih Jin, and Kristopher T. Kahle. Genetic dysregulation of an endothelial ras signaling network in vein of galen malformations. BioRxiv, Mar 2023. URL: https://doi.org/10.1101/2023.03.18.532837, doi:10.1101/2023.03.18.532837. This article has 3 citations.

10. (zhao2023geneticdysregulationof pages 30-35): Shujuan Zhao, Kedous Y. Mekbib, Martijn A. van der Ent, Garrett Allington, Andrew Prendergast, Jocelyn E. Chau, Hannah Smith, John Shohfi, Jack Ocken, Daniel Duran, Charuta G. Furey, Hao Thi Le, Phan Q. Duy, Benjamin C. Reeves, Junhui Zhang, Carol Nelson-Williams, Di Chen, Boyang Li, Timothy Nottoli, Suxia Bai, Myron Rolle, Xue Zeng, Weilai Dong, Po-Ying Fu, Yung-Chun Wang, Shrikant Mane, Paulina Piwowarczyk, Katie Pricola Fehnel, Alfred Pokmeng See, Bermans J. Iskandar, Beverly Aagaard-Kienitz, Adam J. Kundishora, Tyrone DeSpenza, Ana B.W. Greenberg, Seblewengel M. Kidanemariam, Andrew T. Hale, James M. Johnston, Eric M. Jackson, Phillip B. Storm, Shih-Shan Lang, William E. Butler, Bob S. Carter, Paul Chapman, Christopher J. Stapleton, Aman B. Patel, Georges Rodesch, Stanislas Smajda, Alejandro Berenstein, Tanyeri Barak, E. Zeynep Erson-Omay, Hongyu Zhao, Andres Moreno-De-Luca, Mark R. Proctor, Edward R. Smith, Darren B. Orbach, Seth L. Alper, Stefania Nicoli, Titus J. Boggon, Richard P. Lifton, Murat Gunel, Philip D. King, Sheng Chih Jin, and Kristopher T. Kahle. Genetic dysregulation of an endothelial ras signaling network in vein of galen malformations. BioRxiv, Mar 2023. URL: https://doi.org/10.1101/2023.03.18.532837, doi:10.1101/2023.03.18.532837. This article has 3 citations.

11. (zhao2023mutationofkey pages 5-7): Shujuan Zhao, Kedous Y. Mekbib, Martijn A. van der Ent, Garrett Allington, Andrew Prendergast, Jocelyn E. Chau, Hannah Smith, John Shohfi, Jack Ocken, Daniel Duran, Charuta G. Furey, Le Thi Hao, Phan Q. Duy, Benjamin C. Reeves, Junhui Zhang, Carol Nelson-Williams, Di Chen, Boyang Li, Timothy Nottoli, Suxia Bai, Myron Rolle, Xue Zeng, Weilai Dong, Po-Ying Fu, Yung-Chun Wang, Shrikant Mane, Paulina Piwowarczyk, Katie Pricola Fehnel, Alfred Pokmeng See, Bermans J. Iskandar, Beverly Aagaard-Kienitz, Quentin J. Moyer, Evan Dennis, Emre Kiziltug, Adam J. Kundishora, Tyrone DeSpenza, Ana B. W. Greenberg, Seblewengel M. Kidanemariam, Andrew T. Hale, James M. Johnston, Eric M. Jackson, Phillip B. Storm, Shih-Shan Lang, William E. Butler, Bob S. Carter, Paul Chapman, Christopher J. Stapleton, Aman B. Patel, Georges Rodesch, Stanislas Smajda, Alejandro Berenstein, Tanyeri Barak, E. Zeynep Erson-Omay, Hongyu Zhao, Andres Moreno-De-Luca, Mark R. Proctor, Edward R. Smith, Darren B. Orbach, Seth L. Alper, Stefania Nicoli, Titus J. Boggon, Richard P. Lifton, Murat Gunel, Philip D. King, Sheng Chih Jin, and Kristopher T. Kahle. Mutation of key signaling regulators of cerebrovascular development in vein of galen malformations. Nature Communications, Nov 2023. URL: https://doi.org/10.1038/s41467-023-43062-z, doi:10.1038/s41467-023-43062-z. This article has 32 citations and is from a highest quality peer-reviewed journal.

12. (duran2019mutationsinchromatin pages 1-3): Daniel Duran, Xue Zeng, Sheng Chih Jin, Jungmin Choi, Carol Nelson-Williams, Bogdan Yatsula, Jonathan Gaillard, Charuta Gavankar Furey, Qiongshi Lu, Andrew T. Timberlake, Weilai Dong, Michelle A. Sorscher, Erin Loring, Jennifer Klein, August Allocco, Ava Hunt, Sierra Conine, Jason K. Karimy, Mark W. Youngblood, Jinwei Zhang, Michael L. DiLuna, Charles C. Matouk, Shrikant Mane, Irina R. Tikhonova, Christopher Castaldi, Francesc López-Giráldez, James Knight, Shozeb Haider, Mariya Soban, Seth L. Alper, Masaki Komiyama, Andrew F. Ducruet, Joseph M. Zabramski, Alan Dardik, Brian P. Walcott, Christopher J. Stapleton, Beverly Aagaard-Kienitz, Georges Rodesch, Eric Jackson, Edward R. Smith, Darren B. Orbach, Alejandro Berenstein, Kaya Bilguvar, Miikka Vikkula, Murat Gunel, Richard P. Lifton, and Kristopher T. Kahle. Mutations in chromatin modifier and ephrin signaling genes in vein of galen malformation. Neuron, 101:429-443.e4, Feb 2019. URL: https://doi.org/10.1016/j.neuron.2018.11.041, doi:10.1016/j.neuron.2018.11.041. This article has 90 citations and is from a highest quality peer-reviewed journal.

13. (zhao2023geneticdysregulationof pages 12-14): Shujuan Zhao, Kedous Y. Mekbib, Martijn A. van der Ent, Garrett Allington, Andrew Prendergast, Jocelyn E. Chau, Hannah Smith, John Shohfi, Jack Ocken, Daniel Duran, Charuta G. Furey, Hao Thi Le, Phan Q. Duy, Benjamin C. Reeves, Junhui Zhang, Carol Nelson-Williams, Di Chen, Boyang Li, Timothy Nottoli, Suxia Bai, Myron Rolle, Xue Zeng, Weilai Dong, Po-Ying Fu, Yung-Chun Wang, Shrikant Mane, Paulina Piwowarczyk, Katie Pricola Fehnel, Alfred Pokmeng See, Bermans J. Iskandar, Beverly Aagaard-Kienitz, Adam J. Kundishora, Tyrone DeSpenza, Ana B.W. Greenberg, Seblewengel M. Kidanemariam, Andrew T. Hale, James M. Johnston, Eric M. Jackson, Phillip B. Storm, Shih-Shan Lang, William E. Butler, Bob S. Carter, Paul Chapman, Christopher J. Stapleton, Aman B. Patel, Georges Rodesch, Stanislas Smajda, Alejandro Berenstein, Tanyeri Barak, E. Zeynep Erson-Omay, Hongyu Zhao, Andres Moreno-De-Luca, Mark R. Proctor, Edward R. Smith, Darren B. Orbach, Seth L. Alper, Stefania Nicoli, Titus J. Boggon, Richard P. Lifton, Murat Gunel, Philip D. King, Sheng Chih Jin, and Kristopher T. Kahle. Genetic dysregulation of an endothelial ras signaling network in vein of galen malformations. BioRxiv, Mar 2023. URL: https://doi.org/10.1101/2023.03.18.532837, doi:10.1101/2023.03.18.532837. This article has 3 citations.

14. (NCT07483255 chunk 1): Darren Orbach. A Phase II Trial of Fetal Embolization for Vein of Galen Malformation. Darren Orbach. 2026. ClinicalTrials.gov Identifier: NCT07483255

15. (NCT04434729 chunk 1): Darren Orbach. Fetal Treatment of Galenic Malformations. Darren Orbach. 2022. ClinicalTrials.gov Identifier: NCT04434729

Artifacts

• Edison artifact artifact-00

Reference Validation

Checked with linkml-reference-validator 0.2.1.

All extracted references resolved successfully.