| Domain | Knowledge-base fact | Quantitative data | Evidence type/year | Ontology suggestions |
|---|---|---|---|---|
| Definition & anatomic determinants **(DORV-specific)** | DORV is defined by both great arteries arising primarily from the morphologic right ventricle; practical classification depends on **VSD location**, **great-artery relationship**, and **presence/level of outflow tract obstruction**, all of which drive surgical strategy and imaging needs. (pqac-00000001) | Represents **1–3% of all CHD**; incidence **3–9 per 100,000 live births**. (pqac-00000001) | Narrative review of pediatric CMR / 2024 (pqac-00000001) | MeSH: Double Outlet Right Ventricle; UBERON: right ventricle, ventricular septum, outflow tract; HPO: Ventricular septal defect, Abnormality of the outflow tract |
| Incidence / population burden **(DORV-specific + general CHD context)** | Available retrieved evidence supports DORV as a rare complex CHD within the conotruncal/outflow-tract spectrum. General CHD prevalence context should not be substituted for DORV prevalence. (pqac-00000001, pqac-00000008) | DORV: **3–9/100,000 live births**; general CHD prevalence in review literature: **9.41 per 1000 live births** globally (not DORV-specific). (pqac-00000001, pqac-00000008) | DORV imaging review / 2024; CHD models review / 2024 (pqac-00000001, pqac-00000008) | MONDO: congenital heart disease / DORV if mapped; MeSH: Heart Defects, Congenital |
| Imaging & preoperative assessment **(DORV-specific)** | Transthoracic echocardiography is first-line for defining anatomy; **preoperative CMR** is valuable for detailed visualization of the VSD and spatial relationships relevant to repair planning; **postoperative CMR** helps evaluate late complications. (pqac-00000001) | No sensitivity/specificity reported in retrieved DORV-specific source; 4D flow noted as useful for estimating RVOT diameters and flow characterization. (pqac-00000001) | Narrative review / 2024 (pqac-00000001) | NCIT: Magnetic Resonance Imaging; LOINC/RadLex terms for echocardiography/CMR; UBERON: right ventricular outflow tract |
| Real-world implementation: virtual surgical planning **(DORV-specific)** | A prospective observational study used standard-of-care **MRI, 3D echo, and CT** to reconstruct patient-specific anatomy and perform **virtual surgery** for complex lesions including DORV, aiming to compare planned vs implemented repairs. (pqac-00000005) | Trial enrollment **66**; age up to **22 years**; study completed. (pqac-00000005) | ClinicalTrials.gov observational study / first posted 2009, last updated 2022 (pqac-00000005) | NCIT: Surgical Planning; NCIT: Three Dimensional Imaging; MeSH: Computer Simulation |
| Genetic testing yield **(general CHD evidence; relevant to DORV workup, not DORV-specific)** | Genetic etiologies are common enough in complex CHD that chromosomal and sequencing-based testing is clinically relevant; CMA is used as a nontargeted first-line approach when a specific syndrome is not suspected. (pqac-00000004, pqac-00000003) | Genetic etiology identifiable in **20–30%** of CHD; postnatal CMA yield **4–28%** in prior CHD studies; in one neonatal cohort, pathogenic CNV in **21.3% (61/287)** by CMA and aneuploidy in additional **11% (58/525)** overall; conotruncal defects had **27.2%** CMA yield. (pqac-00000004) | Retrospective neonatal cohort / 2022; CHD genetics review / 2021 (pqac-00000004, pqac-00000003) | NCIT: Chromosomal Microarray Analysis; NCIT: Exome Sequencing; SO: copy number variant |
| Variant interpretation workflow **(general CHD evidence; relevant to DORV)** | Exome-based CHD studies prioritize rare variants using population frequency filters and classify them with **ACMG/AMP** frameworks, supported by ClinGen/ClinVar/VarSome/Franklin. (pqac-00000003) | Example family-based diagnostic rates cited in the review: **31%** with targeted NGS panels in CHD families; **33%** in one small familial CHD series. (pqac-00000003) | Narrative review / 2021 (pqac-00000003) | NCIT: Genetic Counseling; SO: missense variant, frameshift variant; ECO: clinical sequencing evidence |
| Mechanism: PCP–SHROOM3 **(DORV-specific mechanistic model evidence)** | In mouse, **SHROOM3** functions downstream of noncanonical **Wnt/planar cell polarity (PCP)** signaling; loss of function disrupts cardiomyocyte polarity, actomyosin organization, proliferation, and morphology, producing a CHD spectrum that includes **DORV**. (pqac-00000000) | DORV reported as part of a **variable penetrance spectrum** in Shroom3 knockout mice; no percentage given in retrieved text. (pqac-00000000) | Mouse mechanistic study / 2020 (pqac-00000000) | GO: planar cell polarity pathway; GO: actomyosin structure organization; CL: cardiomyocyte, cardiac neural crest cell, second heart field cell |
| Mechanism: FOXJ1–motile cilia / left-right patterning **(DORV-specific human + model evidence)** | A truncating **FOXJ1** variant identified by clinical exome sequencing was associated with isolated CHD including **DORV** and TGA; functional data support impaired ciliogenesis/transactivation, and Foxj1 loss-of-function mice show abnormal looping and complex CHD including **DORV**, linking DORV to cilia-dependent **left-right organizer/NODAL-axis** biology. (pqac-00000002) | Single reported proband in retrieved paper; CHD overall affects nearly **11 per 1000 newborns** in the paper’s introduction (general, not DORV-specific). (pqac-00000002) | Human genetics + functional assays + mouse model / 2023 (pqac-00000002) | GO: cilium movement; GO: determination of left/right symmetry; CL: ciliated epithelial cell; HPO: Dextrocardia, Transposition of the great arteries |
| Mechanism: retinoic acid / second heart field **(general developmental pathway relevant to DORV)** | Properly controlled **retinoic acid (RA)** signaling is required for outflow-tract elongation and septation by maintaining/differentiating cardiogenic progenitors in the **second heart field**; defective or excess RA signaling is a recognized route to outflow-tract CHD and is therefore mechanistically relevant to DORV. (pqac-00000006) | No DORV-specific frequency in retrieved source. (pqac-00000006) | Developmental biology review / 2019 (pqac-00000006) | GO: retinoic acid receptor signaling pathway; GO: heart development; CL: second heart field progenitor cell |
| Environmental / teratogenic factors **(general CHD evidence; not DORV-specific)** | Retrieved recent review evidence lists environmental contributors to CHD including **dioxins, pesticides, polychlorinated biphenyls**, and maternal exposure to **alcohol, isotretinoin, thalidomide, antiseizure medications, and antiretrovirals**; these should be treated as CHD-level rather than DORV-proven risks unless lesion-specific data are available. (pqac-00000008) | No DORV-specific effect sizes reported in retrieved evidence. (pqac-00000008) | CHD models/background review / 2024 (pqac-00000008) | CHEBI: retinoic acid, ethanol; MeSH: Teratogens |
| Prenatal diagnosis & care pathways **(general complex CHD / single-ventricle context; partly applicable to selected DORV)** | Prenatal echocardiography and fetal cardiac MRI can delineate complex CHD and support **planned delivery at tertiary centers**, improving survival outcomes; this is particularly relevant for DORV cases with functionally univentricular physiology or severe associated lesions. (pqac-00000007) | Most heart malformations recognizable at **16–18 weeks**; reported sensitivity **>96%** and specificity **approaching 100%** in cited review text for prenatal recognition generally. (pqac-00000007) | Narrative review / 2023 (pqac-00000007) | NCIT: Fetal Echocardiography; NCIT: Magnetic Resonance Imaging; HPO: Prenatal onset |
| Treatment pathways **(DORV-specific)** | DORV treatment is anatomy-driven: imaging must define whether **biventricular repair** is feasible and characterize VSD-arterial alignment/outflow obstruction; postoperative CMR surveillance is used for late structural/functional complications. Retrieved evidence supports surgical planning rather than a single universal operation. (pqac-00000001, pqac-00000005) | No single outcome rate supported in retrieved DORV-specific contexts. (pqac-00000001, pqac-00000005) | CMR review / 2024; observational surgical-planning study / 2022 update (pqac-00000001, pqac-00000005) | NCIT: Cardiac Surgical Procedure; NCIT: Biventricular Repair; NCIT: Fontan Procedure |
| Model organisms & experimental systems **(general CHD, includes DORV-relevant models)** | Current CHD model platforms include **mouse, zebrafish, Xenopus, chick, canine, primate, Drosophila, and iPSCs**; for DORV-relevant mechanisms, mouse and zebrafish are especially useful for outflow-tract, cilia, PCP, and second-heart-field biology, while iPSCs support variant interrogation but have maturation/2D limitations. (pqac-00000008, pqac-00000003) | No DORV-specific model prevalence data. (pqac-00000008, pqac-00000003) | Models review / 2024; genetics review / 2021 (pqac-00000008, pqac-00000003) | NCBI Taxon: Mus musculus, Danio rerio, Xenopus; EFO/NCIT: induced pluripotent stem cell |
| Septal anatomy relevant to repair **(general anatomy with direct DORV relevance)** | In hearts with valvar overriding and DORV-related ventricular septal deficiency, the clinically relevant “defect” is the **curved right-ventricular boundary** around which a surgeon places a patch to tunnel flow to the appropriate outflow, underscoring why septal topology matters for DORV repair planning. (pqac-00000009) | No DORV-specific percentages. (pqac-00000009) | Anatomic/pathology review / 2014 (pqac-00000009) | UBERON: ventricular septum; HPO: Overriding aorta; NCIT: Patch Closure |


*Table: This table summarizes DORV-specific facts and carefully separated general CHD evidence relevant to a disease knowledge-base entry. It highlights anatomic determinants, imaging, genetics, developmental mechanisms, treatment planning, and model systems while avoiding unsupported lesion-specific claims.*