Congenital Total Pulmonary Venous Return Anomaly

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Mappings

ICD-10-CM

ICD10CM:Q26.2 Total anomalous pulmonary venous connection

ICD-10-CM Q26.2 is the diagnosis code for total anomalous pulmonary venous connection, the clinical synonym of this MONDO disease.

◆

Subtypes

4

Supracardiac TAPVR

Pulmonary venous drainage connects above the heart.

Show evidence (1 reference)

PMID:16638546 SUPPORT Human Clinical

"It constitutes between 1% and 1.5% of all children with congenital heart disease and can be categorized by the site of drainage into the systemic circulation (supracardiac, 45%; infracardiac, 25%; cardiac, 25%; mixed, 5%)."

The surgical review lists supracardiac TAPVR as one of the standard anatomic drainage-site categories.

Cardiac TAPVR

Pulmonary venous drainage connects at the heart, commonly to the coronary sinus or right atrium.

Show evidence (1 reference)

PMID:16638546 SUPPORT Human Clinical

"It constitutes between 1% and 1.5% of all children with congenital heart disease and can be categorized by the site of drainage into the systemic circulation (supracardiac, 45%; infracardiac, 25%; cardiac, 25%; mixed, 5%)."

The surgical review lists cardiac TAPVR as one of the standard anatomic drainage-site categories.

Infracardiac TAPVR

Pulmonary venous drainage connects below the diaphragm.

Show evidence (1 reference)

PMID:16638546 SUPPORT Human Clinical

"It constitutes between 1% and 1.5% of all children with congenital heart disease and can be categorized by the site of drainage into the systemic circulation (supracardiac, 45%; infracardiac, 25%; cardiac, 25%; mixed, 5%)."

The surgical review lists infracardiac TAPVR as one of the standard anatomic drainage-site categories.

Mixed TAPVR

Pulmonary veins drain through more than one anomalous pathway.

Show evidence (1 reference)

PMID:16638546 SUPPORT Human Clinical

"It constitutes between 1% and 1.5% of all children with congenital heart disease and can be categorized by the site of drainage into the systemic circulation (supracardiac, 45%; infracardiac, 25%; cardiac, 25%; mixed, 5%)."

The surgical review lists mixed TAPVR as one of the standard anatomic drainage-site categories.

⚙

Pathophysiology

2

Anomalous Pulmonary Venous Drainage

Total anomalous drainage returns oxygenated pulmonary venous blood to the right-sided circulation, creating obligatory right-to-left mixing at the atrial level and abnormal pulmonary blood flow.

blood vessel endothelial cell link vascular smooth muscle cell link

pulmonary vein morphogenesis link ⚠ ABNORMAL vasculature development link ⚠ ABNORMAL

Downstream

Pulmonary Venous Obstruction Abnormal anomalous drainage pathways can be narrowed or obstructed, raising pulmonary venous pressure and worsening postnatal compromise.

Show evidence (2 references)

PMID:16638546 SUPPORT Human Clinical

"The diagnosis of total anomalous pulmonary venous connection (TAPVC) is made when all four pulmonary veins drain anomalously to the right atrium or to a tributary of the systemic veins."

This review statement directly supports the defining anomalous pulmonary venous drainage mechanism.

PMID:27594934 SUPPORT Human Clinical

"TAPVC is caused by nonfusion of pulmonary venous confluence with LA, thus, the oxygenated pulmonary blood is redirected to right heart and pumped once again to the lungs"

The imaging case review describes the embryologic failure and resulting redirection of pulmonary venous return.

Pulmonary Venous Obstruction

Narrowed or obstructed anomalous venous pathways can elevate pulmonary venous pressure, worsening cyanosis, pulmonary edema, and pulmonary hypertension.

blood vessel endothelial cell link vascular smooth muscle cell link

blood vessel morphogenesis link ⚠ ABNORMAL

Downstream

Cyanosis Obstructed pulmonary venous return worsens systemic desaturation and respiratory compromise.

Show evidence (2 references)

PMID:16638546 SUPPORT Human Clinical

"The clinical presentation is different if the pulmonary venous drainage is unobstructed (heart failure, mild cyanosis) or obstructed (respiratory failure, severe heart failure)."

The review distinguishes obstructed from unobstructed TAPVR and links obstruction to more severe clinical compromise.

PMID:38988666 SUPPORT Human Clinical

"Our results suggest that a pre-discharge echocardiography Doppler velocity threshold of 1.2 m/s could serve as a critical predictor for reoperation, emphasizing the need for targeted follow-up strategies for at-risk patients."

The postoperative cohort supports pulmonary vein obstruction as an important post-repair risk marker requiring follow-up.

⬡

Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.

●

Phenotypes

5

Cardiovascular 2

Pulmonary Arterial Hypertension Pulmonary arterial hypertension (HP:0002092)

Show evidence (1 reference)

PMID:27594934 SUPPORT Human Clinical

"Based on its type and degree of pulmonary venous obstruction, TAPVC may result in pulmonary hypertension and congestive heart failure"

The imaging case review links TAPVR severity and obstruction to pulmonary hypertension.

Congestive Heart Failure Congestive heart failure (HP:0001635)

Show evidence (1 reference)

PMID:16638546 SUPPORT Human Clinical

"The clinical presentation is different if the pulmonary venous drainage is unobstructed (heart failure, mild cyanosis) or obstructed (respiratory failure, severe heart failure)."

The surgical review explicitly links TAPVR presentation to heart failure, particularly severe heart failure when pulmonary venous drainage is obstructed.

Integument 1

Cyanosis Cyanosis (HP:0000961)

Show evidence (1 reference)

PMID:16638546 SUPPORT Human Clinical

"The clinical presentation is different if the pulmonary venous drainage is unobstructed (heart failure, mild cyanosis) or obstructed (respiratory failure, severe heart failure)."

The review names cyanosis as a clinical manifestation of unobstructed TAPVR and severe compromise in obstructed TAPVR.

Respiratory 1

Respiratory Distress Respiratory distress (HP:0002098)

Show evidence (1 reference)

PMID:16638546 SUPPORT Human Clinical

"The clinical presentation is different if the pulmonary venous drainage is unobstructed (heart failure, mild cyanosis) or obstructed (respiratory failure, severe heart failure)."

The surgical review directly identifies respiratory failure as a presenting feature of obstructed total anomalous pulmonary venous return.

Other 1

Total Anomalous Pulmonary Venous Return OBLIGATE Total anomalous pulmonary venous return (HP:0005160)

Show evidence (1 reference)

PMID:16638546 SUPPORT Human Clinical

"The diagnosis of total anomalous pulmonary venous connection (TAPVC) is made when all four pulmonary veins drain anomalously to the right atrium or to a tributary of the systemic veins."

This directly supports total anomalous pulmonary venous return as the defining phenotype.

🧬

Genetic Associations

1

TBX5 (Associated)

Show evidence (1 reference)

PMID:35514310 PARTIAL Human Clinical

"The present findings extended the phenotypic cardiac defects associated with HOS; to the best of our knowledge, this is the first association of mixed‑type TAPVR with TBX5."

This family-based report supports TBX5 as a syndromic association for mixed‑type TAPVR, not as a universal cause of isolated TAPVR.

💊

Treatments

1

Surgical Repair

Action: surgical procedure MAXO:0000004

Surgical redirection of pulmonary venous drainage to the left atrium is the definitive treatment, with urgent repair required when venous obstruction is present.

Target Phenotypes: Total anomalous pulmonary venous return ↗

Show evidence (2 references)

PMID:16638546 SUPPORT Human Clinical

"Obstructed TAPVC requires urgent surgical intervention, whereas unobstructed TAPVC can be dealt with electively; although this is usually operated on once the diagnosis is made."

The review supports surgical repair as definitive management and distinguishes urgent management of obstructed TAPVR.

PMID:36713670 SUPPORT Human Clinical

"The primary sutureless technique may eliminate the differences between subtypes while decrease the postoperative PVO rate, which makes it applicable in any subtypes of TAPVC."

The 80-patient surgical series supports modern operative repair and postoperative obstruction prevention strategies.

{ }

Source YAML

click to show

name: Congenital Total Pulmonary Venous Return Anomaly
creation_date: "2026-05-06T03:15:55Z"
updated_date: "2026-05-06T03:15:55Z"
category: Congenital Cardiovascular Disorder
parents:
- Heart Disorder
- Vascular Disorder
disease_term:
  preferred_term: congenital total pulmonary venous return anomaly
  term:
    id: MONDO:0007130
    label: congenital total pulmonary venous return anomaly
mappings:
  icd10cm_mappings:
  - term:
      id: ICD10CM:Q26.2
      label: Total anomalous pulmonary venous connection
    mapping_predicate: skos:exactMatch
    mapping_source: ICD-10-CM
    mapping_justification: ICD-10-CM Q26.2 is the diagnosis code for total anomalous pulmonary venous connection, the clinical synonym of this MONDO disease.
description: >-
  Congenital total pulmonary venous return anomaly, also called total anomalous
  pulmonary venous return, is a congenital pulmonary venous malformation in
  which all pulmonary veins drain to the right atrium or systemic venous
  circulation instead of the left atrium.
synonyms:
- Total anomalous pulmonary venous connection
- Total anomalous pulmonary venous return
- TAPVC
- TAPVR
has_subtypes:
- name: Supracardiac
  display_name: Supracardiac TAPVR
  description: Pulmonary venous drainage connects above the heart.
  evidence:
  - reference: PMID:16638546
    reference_title: Surgical repair of total anomalous pulmonary venous connection.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "It constitutes between 1% and 1.5% of all children with congenital heart disease and can be categorized by the site of drainage into the systemic circulation (supracardiac, 45%; infracardiac, 25%; cardiac, 25%; mixed, 5%)."
    explanation: >-
      The surgical review lists supracardiac TAPVR as one of the standard
      anatomic drainage-site categories.
- name: Cardiac
  display_name: Cardiac TAPVR
  description: Pulmonary venous drainage connects at the heart, commonly to the coronary sinus or right atrium.
  evidence:
  - reference: PMID:16638546
    reference_title: Surgical repair of total anomalous pulmonary venous connection.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "It constitutes between 1% and 1.5% of all children with congenital heart disease and can be categorized by the site of drainage into the systemic circulation (supracardiac, 45%; infracardiac, 25%; cardiac, 25%; mixed, 5%)."
    explanation: >-
      The surgical review lists cardiac TAPVR as one of the standard anatomic
      drainage-site categories.
- name: Infracardiac
  display_name: Infracardiac TAPVR
  description: Pulmonary venous drainage connects below the diaphragm.
  evidence:
  - reference: PMID:16638546
    reference_title: Surgical repair of total anomalous pulmonary venous connection.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "It constitutes between 1% and 1.5% of all children with congenital heart disease and can be categorized by the site of drainage into the systemic circulation (supracardiac, 45%; infracardiac, 25%; cardiac, 25%; mixed, 5%)."
    explanation: >-
      The surgical review lists infracardiac TAPVR as one of the standard
      anatomic drainage-site categories.
- name: Mixed
  display_name: Mixed TAPVR
  description: Pulmonary veins drain through more than one anomalous pathway.
  evidence:
  - reference: PMID:16638546
    reference_title: Surgical repair of total anomalous pulmonary venous connection.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "It constitutes between 1% and 1.5% of all children with congenital heart disease and can be categorized by the site of drainage into the systemic circulation (supracardiac, 45%; infracardiac, 25%; cardiac, 25%; mixed, 5%)."
    explanation: >-
      The surgical review lists mixed TAPVR as one of the standard anatomic
      drainage-site categories.
pathophysiology:
- name: Anomalous Pulmonary Venous Drainage
  description: >-
    Total anomalous drainage returns oxygenated pulmonary venous blood to the
    right-sided circulation, creating obligatory right-to-left mixing at the
    atrial level and abnormal pulmonary blood flow.
  cell_types:
  - preferred_term: blood vessel endothelial cell
    term:
      id: CL:0000071
      label: blood vessel endothelial cell
  - preferred_term: vascular smooth muscle cell
    term:
      id: CL:0000359
      label: vascular associated smooth muscle cell
  biological_processes:
  - preferred_term: pulmonary vein morphogenesis
    term:
      id: GO:0060577
      label: pulmonary vein morphogenesis
    modifier: ABNORMAL
  - preferred_term: vasculature development
    term:
      id: GO:0001944
      label: vasculature development
    modifier: ABNORMAL
  evidence:
  - reference: PMID:16638546
    reference_title: Surgical repair of total anomalous pulmonary venous connection.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The diagnosis of total anomalous pulmonary venous connection (TAPVC) is made when all four pulmonary veins drain anomalously to the right atrium or to a tributary of the systemic veins."
    explanation: >-
      This review statement directly supports the defining anomalous pulmonary
      venous drainage mechanism.
  - reference: PMID:27594934
    reference_title: Computed tomography features of supracardiac total anomalous pulmonary venous connection in an infant.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "TAPVC is caused by nonfusion of pulmonary venous confluence with LA, thus, the oxygenated pulmonary blood is redirected to right heart and pumped once again to the lungs"
    explanation: >-
      The imaging case review describes the embryologic failure and resulting
      redirection of pulmonary venous return.
  downstream:
  - target: Pulmonary Venous Obstruction
    description: Abnormal anomalous drainage pathways can be narrowed or obstructed, raising pulmonary venous pressure and worsening postnatal compromise.
- name: Pulmonary Venous Obstruction
  description: >-
    Narrowed or obstructed anomalous venous pathways can elevate pulmonary
    venous pressure, worsening cyanosis, pulmonary edema, and pulmonary
    hypertension.
  cell_types:
  - preferred_term: blood vessel endothelial cell
    term:
      id: CL:0000071
      label: blood vessel endothelial cell
  - preferred_term: vascular smooth muscle cell
    term:
      id: CL:0000359
      label: vascular associated smooth muscle cell
  biological_processes:
  - preferred_term: blood vessel morphogenesis
    term:
      id: GO:0048514
      label: blood vessel morphogenesis
    modifier: ABNORMAL
  evidence:
  - reference: PMID:16638546
    reference_title: Surgical repair of total anomalous pulmonary venous connection.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The clinical presentation is different if the pulmonary venous drainage is unobstructed (heart failure, mild cyanosis) or obstructed (respiratory failure, severe heart failure)."
    explanation: >-
      The review distinguishes obstructed from unobstructed TAPVR and links
      obstruction to more severe clinical compromise.
  - reference: PMID:38988666
    reference_title: "Assessing the risk of reoperation for mild pulmonary vein obstruction post-TAPVC repair: a retrospective cohort study."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Our results suggest that a pre-discharge echocardiography Doppler velocity threshold of 1.2 m/s could serve as a critical predictor for reoperation, emphasizing the need for targeted follow-up strategies for at-risk patients."
    explanation: >-
      The postoperative cohort supports pulmonary vein obstruction as an
      important post-repair risk marker requiring follow-up.
  downstream:
  - target: Cyanosis
    description: Obstructed pulmonary venous return worsens systemic desaturation and respiratory compromise.
phenotypes:
- name: Total Anomalous Pulmonary Venous Return
  category: Cardiovascular
  frequency: OBLIGATE
  phenotype_term:
    preferred_term: Total anomalous pulmonary venous return
    term:
      id: HP:0005160
      label: Total anomalous pulmonary venous return
  description: >-
    All pulmonary veins drain anomalously rather than connecting normally to
    the left atrium.
  evidence:
  - reference: PMID:16638546
    reference_title: Surgical repair of total anomalous pulmonary venous connection.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The diagnosis of total anomalous pulmonary venous connection (TAPVC) is made when all four pulmonary veins drain anomalously to the right atrium or to a tributary of the systemic veins."
    explanation: >-
      This directly supports total anomalous pulmonary venous return as the
      defining phenotype.
- name: Cyanosis
  category: Cardiovascular
  phenotype_term:
    preferred_term: Cyanosis
    term:
      id: HP:0000961
      label: Cyanosis
  description: >-
    Systemic desaturation results from obligatory mixing of pulmonary and
    systemic venous blood.
  evidence:
  - reference: PMID:16638546
    reference_title: Surgical repair of total anomalous pulmonary venous connection.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The clinical presentation is different if the pulmonary venous drainage is unobstructed (heart failure, mild cyanosis) or obstructed (respiratory failure, severe heart failure)."
    explanation: >-
      The review names cyanosis as a clinical manifestation of unobstructed
      TAPVR and severe compromise in obstructed TAPVR.
- name: Respiratory Distress
  category: Respiratory
  phenotype_term:
    preferred_term: Respiratory distress
    term:
      id: HP:0002098
      label: Respiratory distress
  description: >-
    Obstructed TAPVR can present with severe respiratory compromise due to
    pulmonary venous hypertension and pulmonary edema.
  evidence:
  - reference: PMID:16638546
    reference_title: Surgical repair of total anomalous pulmonary venous connection.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The clinical presentation is different if the pulmonary venous drainage is unobstructed (heart failure, mild cyanosis) or obstructed (respiratory failure, severe heart failure)."
    explanation: >-
      The surgical review directly identifies respiratory failure as a
      presenting feature of obstructed total anomalous pulmonary venous return.
- name: Pulmonary Arterial Hypertension
  category: Cardiovascular
  phenotype_term:
    preferred_term: Pulmonary arterial hypertension
    term:
      id: HP:0002092
      label: Pulmonary arterial hypertension
  description: >-
    Increased pulmonary blood flow and venous obstruction can raise pulmonary
    arterial pressure.
  evidence:
  - reference: PMID:27594934
    reference_title: Computed tomography features of supracardiac total anomalous pulmonary venous connection in an infant.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Based on its type and degree of pulmonary venous obstruction, TAPVC may result in pulmonary hypertension and congestive heart failure"
    explanation: >-
      The imaging case review links TAPVR severity and obstruction to pulmonary
      hypertension.
- name: Congestive Heart Failure
  category: Cardiovascular
  phenotype_term:
    preferred_term: Congestive heart failure
    term:
      id: HP:0001635
      label: Congestive heart failure
  description: >-
    Pulmonary overcirculation and obstructed venous drainage can contribute to
    heart failure, particularly in infancy.
  evidence:
  - reference: PMID:16638546
    reference_title: Surgical repair of total anomalous pulmonary venous connection.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The clinical presentation is different if the pulmonary venous drainage is unobstructed (heart failure, mild cyanosis) or obstructed (respiratory failure, severe heart failure)."
    explanation: >-
      The surgical review explicitly links TAPVR presentation to heart failure,
      particularly severe heart failure when pulmonary venous drainage is
      obstructed.
genetic:
- name: TBX5
  gene_term:
    preferred_term: TBX5
    term:
      id: hgnc:11604
      label: TBX5
  association: Associated
  evidence:
  - reference: PMID:35514310
    reference_title: "TBX5 variant with the novel phenotype of mixed‑type total anomalous pulmonary venous return in Holt‑Oram Syndrome and variable intrafamilial heart defects."
    supports: PARTIAL
    evidence_source: HUMAN_CLINICAL
    snippet: "The present findings extended the phenotypic cardiac defects associated with HOS; to the best of our knowledge, this is the first association of mixed‑type TAPVR with TBX5."
    explanation: >-
      This family-based report supports TBX5 as a syndromic association for
      mixed‑type TAPVR, not as a universal cause of isolated TAPVR.
treatments:
- name: Surgical Repair
  treatment_term:
    preferred_term: surgical procedure
    term:
      id: MAXO:0000004
      label: surgical procedure
  description: >-
    Surgical redirection of pulmonary venous drainage to the left atrium is the
    definitive treatment, with urgent repair required when venous obstruction is
    present.
  target_phenotypes:
  - preferred_term: Total anomalous pulmonary venous return
    term:
      id: HP:0005160
      label: Total anomalous pulmonary venous return
  evidence:
  - reference: PMID:16638546
    reference_title: Surgical repair of total anomalous pulmonary venous connection.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Obstructed TAPVC requires urgent surgical intervention, whereas unobstructed TAPVC can be dealt with electively; although this is usually operated on once the diagnosis is made."
    explanation: >-
      The review supports surgical repair as definitive management and
      distinguishes urgent management of obstructed TAPVR.
  - reference: PMID:36713670
    reference_title: "Total anomalous pulmonary venous connection in 80 patients: Primary sutureless repair and outcomes."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The primary sutureless technique may eliminate the differences between subtypes while decrease the postoperative PVO rate, which makes it applicable in any subtypes of TAPVC."
    explanation: >-
      The 80-patient surgical series supports modern operative repair and
      postoperative obstruction prevention strategies.
references:
- reference: PMID:16638546
  title: Surgical repair of total anomalous pulmonary venous connection.
  findings: []
- reference: PMID:27594934
  title: Computed tomography features of supracardiac total anomalous pulmonary
    venous connection in an infant.
  findings: []
- reference: PMID:36713670
  title: "Total anomalous pulmonary venous connection in 80 patients: Primary sutureless repair and outcomes."
  findings: []
- reference: PMID:38988666
  title: "Assessing the risk of reoperation for mild pulmonary vein obstruction post-TAPVC repair: a retrospective cohort study."
  findings: []
- reference: PMID:35514310
  title: "TBX5 variant with the novel phenotype of mixed‑type total anomalous pulmonary venous return in Holt‑Oram Syndrome and variable intrafamilial heart defects."
  findings: []

📚

References & Deep Research

References

5

PMID:16638546

Surgical repair of total anomalous pulmonary venous connection.

No top-level findings curated for this source.

PMID:27594934

Computed tomography features of supracardiac total anomalous pulmonary venous connection in an infant.

No top-level findings curated for this source.

PMID:36713670

Total anomalous pulmonary venous connection in 80 patients: Primary sutureless repair and outcomes.

No top-level findings curated for this source.

PMID:38988666

Assessing the risk of reoperation for mild pulmonary vein obstruction post-TAPVC repair: a retrospective cohort study.

No top-level findings curated for this source.

PMID:35514310

TBX5 variant with the novel phenotype of mixed‑type total anomalous pulmonary venous return in Holt‑Oram Syndrome and variable intrafamilial heart defects.

No top-level findings curated for this source.

Deep Research

1

Falcon ▸

1. Disease Information

Edison Scientific Literature 36 citations 2026-05-05T23:38:55.696400

1. Disease Information

1.1 Overview (current understanding)

TAPVC/TAPVR is a rare cyanotic congenital heart disease in which oxygenated pulmonary venous blood returns to the right-sided circulation/systemic veins rather than the left atrium, causing systemic desaturation and abnormal pulmonary/systemic blood flow patterns. (cheng2024clinicaldiagnosisand pages 1-4, xue2023prenataldiagnosisand pages 1-2)

A major determinant of early clinical deterioration is pulmonary venous obstruction (PVO) along the anomalous venous pathway, which increases pulmonary venous pressure, drives pulmonary edema, and worsens hypoxemia/hemodynamic compromise. (xue2023prenataldiagnosisand pages 2-3, cheng2024clinicaldiagnosisand pages 4-6)

1.2 Key identifiers and coding systems

ICD-10 (registry definition): Q262 / Q26.2 “Total anomalous pulmonary venous connection” used to identify TAPVC in a nationwide registry study. (henningsen2025nationwideregistrystudy pages 2-3)
Prenatal classification system: Commonly described using the historical Darling classification into four anatomic types: supracardiac, intracardiac/cardiac, infracardiac, and mixed. (cheng2024clinicaldiagnosisand pages 4-6, xue2023prenataldiagnosisand pages 1-2)
MONDO / Orphanet / OMIM / MeSH: Not retrievable from the currently available full-text corpus in this run; therefore not reported here.

1.3 Common synonyms and alternative names

Total anomalous pulmonary venous connection (TAPVC)
Total anomalous pulmonary venous return (TAPVR)
Total anomalous pulmonary venous drainage (TAPVD) (terminology varies across fetal imaging literature) (azab2022tbx5variantwith pages 1-2)

1.4 Evidence provenance (patient-level vs aggregated)

Most information below is derived from aggregated cohorts (fetal cohorts and surgical cohorts), retrospective registries, and review-level synthesis, supplemented by smaller case series. (xue2023prenataldiagnosisand pages 1-2, li2023totalanomalouspulmonary pages 1-2, henningsen2025nationwideregistrystudy pages 2-3)

2. Etiology

2.1 Primary causal factors (mechanistic)

Clinical and surgical literature describes TAPVC/TAPVR as arising from abnormal embryologic development/remodeling of pulmonary venous connections and venous pole structures, with contributions from genetic variation in some patients. (cheng2024clinicaldiagnosisand pages 4-6, xue2023prenataldiagnosisand pages 1-2)

2.2 Genetic risk factors (genes and syndromic associations)

TBX5 (Holt–Oram syndrome expansion): - A pathogenic TBX5 nonsense variant (c.577G>T; p.Gly193) was reported in a family where the proband had mixed-type TAPVR, and subsequent phenotyping supported Holt–Oram syndrome. This report is described as the first genetic investigation* reporting this association. (azab2022tbx5variantwith pages 1-2)

ANKRD1 (candidate gene; gain-of-function signal; mechanistic animal model): - A mechanistic study reports that increased ANKRD1 levels (including gain-of-function contexts) have been associated in humans with TAPVR and motivated creation of a myocardial ANKRD1 overexpression mouse model. In transgenic mice, myocardial ANKRD1 overexpression caused sinus venosus/venous pole remodeling defects with abnormal pulmonary vein–systemic venous communications, linking a plausible developmental mechanism to anomalous venous return phenotypes. (piroddi2020myocardialoverexpressionof pages 1-3, piroddi2020myocardialoverexpressionof pages 7-9, piroddi2020myocardialoverexpressionof pages 3-4)

Associated laterality/heterotaxy context (clinical association): In fetal cohorts, TAPVC frequently co-occurs with complex congenital heart disease and laterality disorders such as right atrial isomerism (a heterotaxy phenotype). (xue2023prenataldiagnosisand pages 7-7, xue2023prenataldiagnosisand pages 8-10)

2.3 Environmental risk/protective factors; GxE

No TAPVC-specific, well-supported protective factors or gene–environment interaction evidence was identified in the retrieved corpus. Environmental teratogen evidence is not established in the extracted TAPVC-focused texts.

3. Phenotypes

3.1 Core clinical presentation (typical)

Neonatal/infant presentations in clinical series commonly include respiratory distress/shortness of breath, cyanosis, recurrent respiratory infections/pneumonia, and heart failure/poor growth—particularly in obstructed forms. (cheng2024clinicaldiagnosisand pages 1-4, cheng2024clinicaldiagnosisand pages 4-6)

3.2 Fetal imaging phenotypes and prenatal “suspicious signs”

A structured fetal echocardiography approach highlighted suspicious ultrasound findings such as: - “a small LA,” “an increased distance from the LA to the descending aorta,” “a smooth posterior wall of the LA,” “unobservable orifices of the PV,” “evident extra vessels and centrifugal venous flow,” and “an abnormal dilated vein (e.g., SVC, INN, AZV, IVC, or CS).” (xue2023prenataldiagnosisand pages 2-3)

3.3 Suggested HPO terms (examples)

Note: HPO IDs are suggested based on phenotype labels; they were not retrieved from an ontology database in this run. - Cyanosis (HP:0000969) - Respiratory distress (HP:0002098) - Tachypnea (HP:0002789) - Recurrent pneumonia (HP:0006532) - Pulmonary venous obstruction/stenosis (concept; may map to Pulmonary vein stenosis (HP:0012728)) - Failure to thrive (HP:0001508)

3.4 Quality of life impact

No TAPVC-specific validated QoL instrument results (e.g., PedsQL, SF-36) were found in the retrieved TAPVC-focused corpus.

4. Genetic / Molecular Information

4.1 Causal genes and pathogenic variants (evidence-supported in retrieved corpus)

TBX5: c.577G>T; p.Gly193* (nonsense; loss-of-function) associated with mixed-type TAPVR in a Holt–Oram syndrome context (family-based trio exome sequencing). (azab2022tbx5variantwith pages 1-2)

4.2 Candidate genes / functional mechanisms

ANKRD1: gain-of-function/dysregulation implicated as a candidate driver of venous pole remodeling defects relevant to anomalous pulmonary venous return; transgenic overexpression produces congenital sinus venosus defects and later diastolic dysfunction. (piroddi2020myocardialoverexpressionof pages 1-3, piroddi2020myocardialoverexpressionof pages 7-9)

4.3 Variant class and origin

TBX5 variant reported: nonsense (likely pathogenic in the report’s interpretation). (azab2022tbx5variantwith pages 1-2)
ANKRD1 evidence in retrieved corpus: gain-of-function/dysregulation signal and experimental overexpression model; specific human variant nomenclature is not fully extractable from the limited snippets provided. (piroddi2020myocardialoverexpressionof pages 3-4, piroddi2020myocardialoverexpressionof pages 1-3)

4.4 Modifier genes, epigenetics, chromosomal abnormalities

No specific, TAPVC-focused modifier gene sets, epigenetic signatures, or recurrent CNVs could be extracted from the retrieved full-text corpus in this run.

5. Environmental Information

No TAPVC-specific environmental, lifestyle, occupational, or infectious causal triggers were identified in the retrieved TAPVC-focused literature.

6. Mechanism / Pathophysiology

6.1 Causal chain (integrated clinical + developmental model)

Developmental misconnection/remodeling failure results in absent direct pulmonary vein–left atrium connection and anomalous drainage to systemic venous pathways/right atrium. (xue2023prenataldiagnosisand pages 1-2, cheng2024clinicaldiagnosisand pages 1-4)
Mixing of oxygenated pulmonary venous blood with systemic venous blood in the right atrium leads to cyanosis/hypoxemia and abnormal loading conditions. (cheng2024clinicaldiagnosisand pages 1-4)
Pulmonary venous obstruction (when present) increases pulmonary venous pressure, aggravating pulmonary congestion and worsening hypoxemia and hemodynamics; obstruction status strongly influences prognosis and urgency of intervention. (xue2023prenataldiagnosisand pages 2-3, cheng2024clinicaldiagnosisand pages 4-6)
Post-repair, some patients develop pulmonary vein stenosis (PVS)/recurrent obstruction, a major driver of reintervention, morbidity, and mortality. (wen2024insightintothe pages 12-14, alifu2024assessingtherisk pages 3-5)

6.2 Molecular/cellular processes (evidence-linked)

ANKRD1 gain-of-function model (mouse): myocardial overexpression causes sinus venosus defects originating from impaired embryonic remodeling, with early transcriptional perturbations involving GATA4 and NKX2-5 and downstream sarcomeric/titin modulation; embryos show abnormal venous pole connections, and adults develop progressive diastolic dysfunction. (piroddi2020myocardialoverexpressionof pages 1-3, piroddi2020myocardialoverexpressionof pages 7-9)

6.3 Suggested ontology mappings

GO (Biological Process) suggestions: - Heart morphogenesis (GO:0003007) - Cardiovascular system development (GO:0072358) - Pulmonary vein development (term exists conceptually; exact GO ID not retrieved in this run) - Blood vessel morphogenesis (GO:0048514)

CL (Cell Ontology) suggestions: - Cardiomyocyte (CL:0000746) - Endothelial cell (CL:0000115) - Cardiac fibroblast (CL term exists; exact ID not retrieved in this run)

UBERON (Anatomy) suggestions: - Pulmonary vein (UBERON term) - Left atrium (UBERON term) - Sinus venosus / venous pole region (UBERON term)

7. Anatomical Structures Affected

7.1 Organ/system level

Primary: pulmonary veins and their confluence, left atrium (failed connection), right atrium/systemic venous pathways receiving pulmonary venous return. (xue2023prenataldiagnosisand pages 1-2, cheng2024clinicaldiagnosisand pages 1-4)
Secondary functional involvement: lungs (pulmonary congestion/edema, especially with obstruction), pulmonary vasculature (risk of pulmonary hypertension), and systemic oxygen delivery (cyanosis). (cheng2024clinicaldiagnosisand pages 4-6, cheng2024clinicaldiagnosisand pages 1-4)

8. Temporal Development

Onset: congenital; often clinically apparent in the neonatal period, especially in obstructed TAPVC. (cheng2024clinicaldiagnosisand pages 4-6)
Course: without surgery, high early mortality is reported; after repair, risk of postoperative pulmonary vein stenosis/obstruction often appears within months and can progress rapidly. (cheng2024clinicaldiagnosisand pages 4-6, wen2024insightintothe pages 12-14)

9. Inheritance and Population

9.1 Epidemiology (selected recent/representative statistics)

TAPVC is described as approximately 2% of congenital heart disease in a recent clinical summary. (cheng2024clinicaldiagnosisand pages 4-6)
In a TBX5-associated report, TAPVR is described as ~7 per 100,000 live births (and ~1–3% of CHD). (azab2022tbx5variantwith pages 1-2)

9.2 Sex ratio / demographics

A clinical summary notes TAPVC is reported more frequently in males than females. (cheng2024clinicaldiagnosisand pages 4-6)

9.3 Inheritance

The retrieved corpus supports heterogeneous genetic architecture: sporadic cases predominate, but rare monogenic syndromic associations (e.g., TBX5 in Holt–Oram) and candidate gene mechanisms (ANKRD1 gain-of-function contexts) exist. (azab2022tbx5variantwith pages 1-2, piroddi2020myocardialoverexpressionof pages 1-3)

10. Diagnostics

10.1 Prenatal diagnosis (real-world implementation)

A fetal cohort describes a four-step prenatal ultrasonography workflow: 1) demonstrate absent PV–LA connections; 2) identify common pulmonary vein and drainage route for subtype classification; 3) assess obstruction (turbulence and max velocity >50 cm/s suggested); 4) assess associated malformations. (xue2023prenataldiagnosisand pages 2-3)

Performance (2023 fetal cohort): diagnostic accuracy by type was reported as 95% (supracardiac), 75% (intracardiac), 95% (infracardiac), 77% (mixed); among isolated TAPVC (n=21), 6 were missed and 1 misclassified prenatally. (xue2023prenataldiagnosisand pages 8-10, xue2023prenataldiagnosisand pages 1-2)

Figure/Table evidence (classification + drainage routes + obstruction): Table 5 from the fetal cohort provides structured subtype and drainage-route detail along with obstruction findings. (xue2023prenataldiagnosisand media 1a8f0ae4)

10.2 Postnatal diagnosis

Transthoracic echocardiography (TTE) is typically first-line but can have mis-/underdiagnosis in some settings.
Computed tomographic angiography (CTA) can increase anatomic diagnostic clarity and can also be used for surgical planning, but introduces radiation/contrast considerations. (cheng2024clinicaldiagnosisand pages 4-6, matsuhisa2020computedtomographybasedsurgical pages 1-2)

10.3 Differential diagnosis (not exhaustively captured in retrieved corpus)

Differentials for cyanotic neonatal CHD with pulmonary overcirculation/respiratory distress may include transposition physiology, obstructed left-sided lesions, and other complex CHD; specific differential algorithms were not retrievable from society guidelines in the current corpus.

11. Outcome / Prognosis

11.1 Natural history without intervention

A clinical summary reports very poor natural prognosis without timely surgical intervention (e.g., mortality up to 48.8% in infancy and high mortality in the first year in severe physiologic circumstances). (cheng2024clinicaldiagnosisand pages 4-6)

11.2 Contemporary surgical outcomes and complications

Review-level synthesis describes early postoperative mortality in published series commonly ranging from <10% to ~20%, with postoperative pulmonary vein stenosis (PVS) as the most common complication and an incidence often cited around 10–20%. (wen2024insightintothe pages 12-14)
In a single-center 2023 series using primary sutureless repair (n=80), there were 2 early deaths and 1 late death, and 2 patients developed postoperative PVO with no reintervention required. (li2023totalanomalouspulmonary pages 1-2)

11.3 Reoperation risk stratification (2024 evidence)

A 2024 cohort found that pre-discharge mild PVO (Doppler velocity >1.2 m/s) was associated with substantially higher reoperation rates; in the fully adjusted model, HR 13.90 (95% CI 1.16–166.5) for reoperation within 1 year. (alifu2024assessingtherisk pages 3-5, alifu2024assessingtherisk pages 5-6)

12. Treatment

12.1 Surgical/interventional treatment (current practice)

Definitive management is surgical repair, typically in the neonatal period when clinically indicated. (cheng2024clinicaldiagnosisand pages 4-6)

Primary sutureless repair (2023 outcomes): In a single-center series (2015–2020), primary sutureless repair across all Darling subtypes showed low postoperative PVO incidence (2/80) and no reintervention, supporting the view that sutureless approaches may reduce anastomotic-level restenosis risk across subtypes. (li2023totalanomalouspulmonary pages 1-2)

Imaging-guided surgical planning (CTA era effect): A 112-patient era comparison reported marked improvement in 5-year survival with a CTA-based strategy (biventricular: 69%→97%; single-ventricle: 21%→70%) and reduced/managed PVS burden with aggressive reintervention. (matsuhisa2020computedtomographybasedsurgical pages 1-2)

Technique comparisons: For supracardiac TAPVC, a modified L-shaped incision approach was associated with improved freedom from death/postoperative PVO versus the posterior technique, especially in those with preoperative obstruction. (feng2020midtermresultsof pages 1-2)

12.2 Supportive perioperative management

Postoperative management may include intensive care strategies and pulmonary hypertension-directed therapies (e.g., inhaled nitric oxide, endothelin receptor antagonists, PDE-5 inhibitors, prostacyclin) as adjuncts when pulmonary hypertension is present. (cheng2024clinicaldiagnosisand pages 4-6)

12.3 Pharmacotherapy / advanced therapeutics

No TAPVC-specific disease-modifying pharmacotherapy trials, gene therapy, or RNA therapeutics were identified in the retrieved corpus.

12.4 Suggested MAXO terms (examples)

Note: MAXO IDs not retrieved in this run; terms suggested as labels. - Surgical repair of congenital heart defect (e.g., “TAPVC repair”) - Sutureless pulmonary venous anastomosis - Computed tomography angiography for preoperative planning - Echocardiographic surveillance / follow-up

13. Prevention

Primary prevention of TAPVC is not established. Practical prevention focuses on: - Secondary prevention via prenatal detection and perinatal planning (delivery at tertiary center; timely neonatal stabilization/surgery). (xue2023prenataldiagnosisand pages 8-10) - Genetic counseling/testing when syndromic features or familial recurrence is suspected (e.g., TBX5/Holt–Oram context). (azab2022tbx5variantwith pages 1-2)

14. Other Species / Natural Disease

No naturally occurring veterinary TAPVC disease series were identified in the retrieved corpus.

15. Model Organisms

A transgenic mouse model with myocardial ANKRD1 overexpression demonstrates congenital venous pole defects (sinus venosus defects; abnormal PV–systemic venous communications) and progressive functional deterioration, providing a mechanistic model relevant to anomalous pulmonary venous return. (piroddi2020myocardialoverexpressionof pages 1-3, piroddi2020myocardialoverexpressionof pages 7-9)

Recent developments (2023–2024 highlights)

Structured fetal diagnostic protocols with quantified type-specific accuracy and documentation that isolated TAPVC is more likely to be missed than syndromic/heterotaxy-associated TAPVC. (xue2023prenataldiagnosisand pages 8-10, xue2023prenataldiagnosisand pages 1-2)
Expansion of sutureless repair evidence showing low postoperative obstruction rates in a 2023 single-center cohort. (li2023totalanomalouspulmonary pages 1-2)
Quantitative echocardiographic risk stratification immediately prior to discharge (1.2 m/s threshold) associated with markedly increased reoperation risk within 1 year. (alifu2024assessingtherisk pages 3-5)

Evidence map of key studies

Topic	Key findings with quantitative stats	Population/Design	Year	Publication (journal)	Identifier (DOI and PMID if available)	URL
Classification / prenatal diagnosis	Four-step prenatal ultrasonography in 62 confirmed fetal TAPVC cases; subtype distribution: supracardiac 20/62 (32%), intracardiac 12/62 (19%), infracardiac 21/62 (34%), mixed 9/62 (15%); prenatal diagnostic accuracy by type: 95%, 75%, 95%, 77%, respectively; among 21 isolated TAPVC cases, 6 were missed and 1 was misclassified prenatally; literature cited in-study reported prenatal PVO prevalence 34.1% (95% CI 22.7%–47.7%); suspicious signs included small LA, increased LA–descending aorta distance, smooth posterior LA wall, absent PV orifices, extra vessels/centrifugal venous flow, and dilated systemic veins; obstruction marker on Doppler: turbulent flow or max velocity >50 cm/s (xue2023prenataldiagnosisand pages 8-10, xue2023prenataldiagnosisand pages 2-3, xue2023prenataldiagnosisand pages 1-2)	Retrospective fetal cohort; prenatal US with postnatal echo/surgery/autopsy confirmation	2023	Frontiers in Pediatrics	DOI: 10.3389/fped.2023.1206032; PMID: not available in context	https://doi.org/10.3389/fped.2023.1206032
Surgery / outcomes	Primary sutureless repair in 80 TAPVC patients: supracardiac 35 (43.8%), cardiac 24 (30%), infracardiac 17 (21.2%), mixed 4 (5%); median age at repair 16.5 days, median weight 3.5 kg; preoperative PVO 20/80 (25%); early deaths 2, late death 1; postoperative PVO in 2 patients, none required reintervention; prolonged CPB time (p=0.009), preoperative pneumonia (p=0.022), and gender (p=0.041) associated with higher postoperative PV flow velocity; authors argue primary sutureless repair may reduce subtype-related differences in postoperative obstruction (li2023totalanomalouspulmonary pages 1-2)	Single-center retrospective surgical series (2015–2020)	2023	Frontiers in Surgery	DOI: 10.3389/fsurg.2022.1086596; PMID: not available in context	https://doi.org/10.3389/fsurg.2022.1086596
Postoperative obstruction predictors	Mild pre-discharge pulmonary vein obstruction defined as Doppler velocity >1.2 m/s; postoperative mild obstruction present in 12/38 (31.6%); median follow-up 10.0 months; reoperation within 1 year was higher with mild obstruction (33.3% vs 7.7%); fully adjusted HR for reoperation 13.90 (95% CI 1.16–166.5), with threshold analysis supporting 1.2 m/s as a practical cutoff for intensified follow-up; routine follow-up echo at 1, 3, 6, and 12 months (alifu2024assessingtherisk pages 1-2, alifu2024assessingtherisk pages 5-6, alifu2024assessingtherisk pages 3-5, alifu2024assessingtherisk pages 2-3)	Single-center retrospective cohort after TAPVC repair	2024	Frontiers in Cardiovascular Medicine	DOI: 10.3389/fcvm.2024.1399659; PMID: not available in context	https://doi.org/10.3389/fcvm.2024.1399659
Surgery / outcomes / imaging-guided planning	CTA-based surgical planning in 112 repaired TAPVC patients comparing era 1 (1996–2010, n=56) vs era 2 (2011–2018, n=56); 5-year survival in biventricular hearts improved from 69% to 97% (P=0.0024); in single-ventricle hearts from 21% to 70% (P=0.0007); post-repair PVS in biventricular hearts fell from 23% to 13%, and in single-ventricle hearts from 60% to 36%; since 2011, 12 patients with post-repair PVS had multiple reinterventions with 5-year survival 88%; preoperative CTA associated with improved survival and PVS-free survival (matsuhisa2020computedtomographybasedsurgical pages 1-2)	Retrospective era-comparison cohort	2020	European Journal of Cardio-Thoracic Surgery	DOI: 10.1093/ejcts/ezaa028; PMID: not available in context	https://doi.org/10.1093/ejcts/ezaa028
Surgery / technique comparison	Modified L-shaped incision vs posterior technique for supracardiac TAPVC in 121 patients (53 vs 68; matched 52 pairs); median follow-up 33 months; operative mortality 5/121 (4.1%), late mortality 12/121 (9.9%); postoperative PVO in 21 patients overall; in matched patients with preoperative PVO, freedom from death and postoperative PVO at 1 and 3 years was 100% and 85.7% in L-shaped group vs 90% and 22.9% in posterior-technique group (P=0.002); posterior technique independently increased risk of death/PVO (HR 4.12, 95% CI 1.12–15.16; P=0.03) (feng2020midtermresultsof pages 1-2)	Single-center retrospective comparative study with propensity matching	2020	European Journal of Cardio-Thoracic Surgery	DOI: 10.1093/ejcts/ezaa264; PMID: not available in context	https://doi.org/10.1093/ejcts/ezaa264
Genetics / molecular	First genetically confirmed association of mixed-type TAPVR with Holt-Oram syndrome due to TBX5 nonsense variant c.577G>T (p.Gly193*); trio WES identified cosegregating variant; study notes TAPVR accounts for ~1–3% of CHD and ~7 per 100,000 live births; protein modeling indicated reduced non-covalent bonding and impaired DNA-binding stability of mutant TBX5; expands cardiac phenotype spectrum for TBX5/HOS (azab2022tbx5variantwith pages 1-2)	Family-based human genetic case report with trio exome sequencing	2022	Molecular Medicine Reports	DOI: 10.3892/mmr.2022.12726; PMID: not available in context	https://doi.org/10.3892/mmr.2022.12726
Genetics / molecular / model organism	ANKRD1 gain-of-function/overexpression linked to anomalous pulmonary venous return biology: prior human evidence cited TAPVR patients with ANKRD1 dysregulation (3–4-fold transcript increase or 10–20% protein-stability increase); myocardial ANKRD1-overexpressing transgenic mice developed sinus venosus defects with anomalous PV–systemic venous communications, venous-pole remodeling defects, early GATA4/Nkx2.5 upregulation, and progressive diastolic dysfunction/heart failure; provides mechanistic support for ANKRD1 as a TAPVR candidate gene (piroddi2020myocardialoverexpressionof pages 3-4, piroddi2020myocardialoverexpressionof pages 12-13, piroddi2020myocardialoverexpressionof pages 1-3, piroddi2020myocardialoverexpressionof pages 7-9)	Transgenic mouse model with supporting human candidate-gene context	2020	Cardiovascular Research	DOI: 10.1093/cvr/cvz291; PMID: not available in context	https://doi.org/10.1093/cvr/cvz291

Table: This table condenses high-value recent and foundational studies on TAPVC/TAPVR across prenatal diagnosis, operative strategy, postoperative obstruction risk, and genetics. It is useful as a quick-reference evidence map for building a disease knowledge base entry.

Key visual evidence

The following table image (from a 2023 fetal cohort) summarizes TAPVC anatomic subtypes, drainage routes, and obstruction findings, supporting the classification and prenatal evaluation sections. (xue2023prenataldiagnosisand media 1a8f0ae4)

Limitations of this report (data availability)

MONDO/Orphanet/OMIM/MeSH identifiers, formal guideline documents, and TAPVC-specific QoL datasets were not retrievable in the accessible corpus for this run; therefore, these elements are flagged as unavailable rather than inferred.
Some epidemiology estimates are study-/setting-specific; population-level prevalence estimates vary by ascertainment method and inclusion criteria.

References

(cheng2024clinicaldiagnosisand pages 1-4): Weiping Cheng, Junzhao Zhu, Youbo Xu, Yingqiang Guo, and Lexiang Shi. Clinical diagnosis and treatment of 5 cases of tapcv in infants. Unknown journal, Oct 2024. URL: https://doi.org/10.21203/rs.3.rs-3480976/v1, doi:10.21203/rs.3.rs-3480976/v1.
(xue2023prenataldiagnosisand pages 1-2): Xiaoying Xue, Qiumei Wu, Mingtao Xiong, Wen Ling, Shan Guo, Hong Ma, Biying Huang, Min Liu, Xiuqing Qiu, and Zongjie Weng. Prenatal diagnosis and postnatal verification in fetuses with total anomalous pulmonary venous connection. Frontiers in Pediatrics, Jun 2023. URL: https://doi.org/10.3389/fped.2023.1206032, doi:10.3389/fped.2023.1206032. This article has 6 citations.
(xue2023prenataldiagnosisand pages 2-3): Xiaoying Xue, Qiumei Wu, Mingtao Xiong, Wen Ling, Shan Guo, Hong Ma, Biying Huang, Min Liu, Xiuqing Qiu, and Zongjie Weng. Prenatal diagnosis and postnatal verification in fetuses with total anomalous pulmonary venous connection. Frontiers in Pediatrics, Jun 2023. URL: https://doi.org/10.3389/fped.2023.1206032, doi:10.3389/fped.2023.1206032. This article has 6 citations.
(cheng2024clinicaldiagnosisand pages 4-6): Weiping Cheng, Junzhao Zhu, Youbo Xu, Yingqiang Guo, and Lexiang Shi. Clinical diagnosis and treatment of 5 cases of tapcv in infants. Unknown journal, Oct 2024. URL: https://doi.org/10.21203/rs.3.rs-3480976/v1, doi:10.21203/rs.3.rs-3480976/v1.
(henningsen2025nationwideregistrystudy pages 2-3): Maj Beldring Henningsen, Cathrine Bohnstedt, Therese Risom Vestergaard, Morten Holdgaard Smerup, Pi Vejsig Madsen, and Lone Graff Stensballe. Nationwide registry study of long term survival and comorbidities in total anomalous pulmonary venous connection in denmark. Scientific Reports, Aug 2025. URL: https://doi.org/10.1038/s41598-025-15769-0, doi:10.1038/s41598-025-15769-0. This article has 3 citations and is from a peer-reviewed journal.
(azab2022tbx5variantwith pages 1-2): Bilal Azab, Dunia Aburizeg, Weizhen Ji, Lauren Jeffries, Nooredeen Isbeih, Amal Al‑Akily, Hashim Mohammad, Yousef Osba, Mohammad Shahin, Zain Dardas, Ma'mon Hatmal, Iyad Al‑Ammouri, and Saquib Lakhani. Tbx5 variant with the novel phenotype of mixed-type total anomalous pulmonary venous return in holt-oram syndrome and variable intrafamilial heart defects. Molecular Medicine Reports, May 2022. URL: https://doi.org/10.3892/mmr.2022.12726, doi:10.3892/mmr.2022.12726. This article has 11 citations and is from a peer-reviewed journal.
(li2023totalanomalouspulmonary pages 1-2): Gefei Li, Baoying Meng, Cheng Zhang, Weimin Zhang, Xiaodong Zhou, Qing Zhang, and Yiqun Ding. Total anomalous pulmonary venous connection in 80 patients: primary sutureless repair and outcomes. Frontiers in Surgery, Jan 2023. URL: https://doi.org/10.3389/fsurg.2022.1086596, doi:10.3389/fsurg.2022.1086596. This article has 5 citations.
(piroddi2020myocardialoverexpressionof pages 1-3): Nicoletta Piroddi, Paola Pesce, Beatrice Scellini, Stefano Manzini, Giulia S Ganzetti, Ileana Badi, Michela Menegollo, Virginia Cora, Simone Tiso, Raffaella Cinquetti, Laura Monti, Giulia Chiesa, Steven B Bleyl, Marco Busnelli, Federica Dellera, Daniele Bruno, Federico Caicci, Annalisa Grimaldi, Roberto Taramelli, Lucia Manni, David Sacerdoti, Chiara Tesi, Corrado Poggesi, Simonetta Ausoni, Francesco Acquati, and Marina Campione. Myocardial overexpression of ankrd1 causes sinus venosus defects and progressive diastolic dysfunction. Cardiovascular research, 116:1458-1472, Nov 2020. URL: https://doi.org/10.1093/cvr/cvz291, doi:10.1093/cvr/cvz291. This article has 40 citations and is from a domain leading peer-reviewed journal.
(piroddi2020myocardialoverexpressionof pages 7-9): Nicoletta Piroddi, Paola Pesce, Beatrice Scellini, Stefano Manzini, Giulia S Ganzetti, Ileana Badi, Michela Menegollo, Virginia Cora, Simone Tiso, Raffaella Cinquetti, Laura Monti, Giulia Chiesa, Steven B Bleyl, Marco Busnelli, Federica Dellera, Daniele Bruno, Federico Caicci, Annalisa Grimaldi, Roberto Taramelli, Lucia Manni, David Sacerdoti, Chiara Tesi, Corrado Poggesi, Simonetta Ausoni, Francesco Acquati, and Marina Campione. Myocardial overexpression of ankrd1 causes sinus venosus defects and progressive diastolic dysfunction. Cardiovascular research, 116:1458-1472, Nov 2020. URL: https://doi.org/10.1093/cvr/cvz291, doi:10.1093/cvr/cvz291. This article has 40 citations and is from a domain leading peer-reviewed journal.
(piroddi2020myocardialoverexpressionof pages 3-4): Nicoletta Piroddi, Paola Pesce, Beatrice Scellini, Stefano Manzini, Giulia S Ganzetti, Ileana Badi, Michela Menegollo, Virginia Cora, Simone Tiso, Raffaella Cinquetti, Laura Monti, Giulia Chiesa, Steven B Bleyl, Marco Busnelli, Federica Dellera, Daniele Bruno, Federico Caicci, Annalisa Grimaldi, Roberto Taramelli, Lucia Manni, David Sacerdoti, Chiara Tesi, Corrado Poggesi, Simonetta Ausoni, Francesco Acquati, and Marina Campione. Myocardial overexpression of ankrd1 causes sinus venosus defects and progressive diastolic dysfunction. Cardiovascular research, 116:1458-1472, Nov 2020. URL: https://doi.org/10.1093/cvr/cvz291, doi:10.1093/cvr/cvz291. This article has 40 citations and is from a domain leading peer-reviewed journal.
(xue2023prenataldiagnosisand pages 7-7): Xiaoying Xue, Qiumei Wu, Mingtao Xiong, Wen Ling, Shan Guo, Hong Ma, Biying Huang, Min Liu, Xiuqing Qiu, and Zongjie Weng. Prenatal diagnosis and postnatal verification in fetuses with total anomalous pulmonary venous connection. Frontiers in Pediatrics, Jun 2023. URL: https://doi.org/10.3389/fped.2023.1206032, doi:10.3389/fped.2023.1206032. This article has 6 citations.
(xue2023prenataldiagnosisand pages 8-10): Xiaoying Xue, Qiumei Wu, Mingtao Xiong, Wen Ling, Shan Guo, Hong Ma, Biying Huang, Min Liu, Xiuqing Qiu, and Zongjie Weng. Prenatal diagnosis and postnatal verification in fetuses with total anomalous pulmonary venous connection. Frontiers in Pediatrics, Jun 2023. URL: https://doi.org/10.3389/fped.2023.1206032, doi:10.3389/fped.2023.1206032. This article has 6 citations.
(wen2024insightintothe pages 12-14): Chen Wen, Geng Shen, Chenhao Fang, and Lan Tian. Insight into the research history and trends of total anomalous pulmonary venous connection: a bibliometric analysis. Journal of Cardiothoracic Surgery, May 2024. URL: https://doi.org/10.1186/s13019-024-02787-8, doi:10.1186/s13019-024-02787-8. This article has 6 citations and is from a peer-reviewed journal.
(alifu2024assessingtherisk pages 3-5): Ailixiati Alifu, Haifan Wang, and Renwei Chen. Assessing the risk of reoperation for mild pulmonary vein obstruction post-tapvc repair: a retrospective cohort study. Frontiers in Cardiovascular Medicine, Jun 2024. URL: https://doi.org/10.3389/fcvm.2024.1399659, doi:10.3389/fcvm.2024.1399659. This article has 2 citations and is from a peer-reviewed journal.
(xue2023prenataldiagnosisand media 1a8f0ae4): Xiaoying Xue, Qiumei Wu, Mingtao Xiong, Wen Ling, Shan Guo, Hong Ma, Biying Huang, Min Liu, Xiuqing Qiu, and Zongjie Weng. Prenatal diagnosis and postnatal verification in fetuses with total anomalous pulmonary venous connection. Frontiers in Pediatrics, Jun 2023. URL: https://doi.org/10.3389/fped.2023.1206032, doi:10.3389/fped.2023.1206032. This article has 6 citations.
(matsuhisa2020computedtomographybasedsurgical pages 1-2): Hironori Matsuhisa, Yoshihiro Oshima, Tomonori Higuma, Shunsuke Matsushima, Shota Hasegawa, Yuson Wada, Michio Matsuoka, and Toshikatsu Tanaka. Computed tomography-based surgical strategy for total anomalous pulmonary venous connection. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, 58:237-245, Feb 2020. URL: https://doi.org/10.1093/ejcts/ezaa028, doi:10.1093/ejcts/ezaa028. This article has 8 citations.
(alifu2024assessingtherisk pages 5-6): Ailixiati Alifu, Haifan Wang, and Renwei Chen. Assessing the risk of reoperation for mild pulmonary vein obstruction post-tapvc repair: a retrospective cohort study. Frontiers in Cardiovascular Medicine, Jun 2024. URL: https://doi.org/10.3389/fcvm.2024.1399659, doi:10.3389/fcvm.2024.1399659. This article has 2 citations and is from a peer-reviewed journal.
(feng2020midtermresultsof pages 1-2): Zicong Feng, Yang Yang, Fengpu He, Kunjing Pang, Kai Ma, Sen Zhang, Lei Qi, Guanxi Wang, Fengqun Mao, Jianhui Yuan, and Shoujun Li. Mid-term results of modified l-shaped incision technique for supracardiac total anomalous pulmonary venous connection. European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery, 58:1261-1268, Sep 2020. URL: https://doi.org/10.1093/ejcts/ezaa264, doi:10.1093/ejcts/ezaa264. This article has 9 citations.
(alifu2024assessingtherisk pages 1-2): Ailixiati Alifu, Haifan Wang, and Renwei Chen. Assessing the risk of reoperation for mild pulmonary vein obstruction post-tapvc repair: a retrospective cohort study. Frontiers in Cardiovascular Medicine, Jun 2024. URL: https://doi.org/10.3389/fcvm.2024.1399659, doi:10.3389/fcvm.2024.1399659. This article has 2 citations and is from a peer-reviewed journal.
(alifu2024assessingtherisk pages 2-3): Ailixiati Alifu, Haifan Wang, and Renwei Chen. Assessing the risk of reoperation for mild pulmonary vein obstruction post-tapvc repair: a retrospective cohort study. Frontiers in Cardiovascular Medicine, Jun 2024. URL: https://doi.org/10.3389/fcvm.2024.1399659, doi:10.3389/fcvm.2024.1399659. This article has 2 citations and is from a peer-reviewed journal.
(piroddi2020myocardialoverexpressionof pages 12-13): Nicoletta Piroddi, Paola Pesce, Beatrice Scellini, Stefano Manzini, Giulia S Ganzetti, Ileana Badi, Michela Menegollo, Virginia Cora, Simone Tiso, Raffaella Cinquetti, Laura Monti, Giulia Chiesa, Steven B Bleyl, Marco Busnelli, Federica Dellera, Daniele Bruno, Federico Caicci, Annalisa Grimaldi, Roberto Taramelli, Lucia Manni, David Sacerdoti, Chiara Tesi, Corrado Poggesi, Simonetta Ausoni, Francesco Acquati, and Marina Campione. Myocardial overexpression of ankrd1 causes sinus venosus defects and progressive diastolic dysfunction. Cardiovascular research, 116:1458-1472, Nov 2020. URL: https://doi.org/10.1093/cvr/cvz291, doi:10.1093/cvr/cvz291. This article has 40 citations and is from a domain leading peer-reviewed journal.

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References & Deep Research

References

Deep Research

1. Disease Information

1.1 Overview (current understanding)

1.2 Key identifiers and coding systems

1.3 Common synonyms and alternative names

1.4 Evidence provenance (patient-level vs aggregated)

2. Etiology

2.1 Primary causal factors (mechanistic)

2.2 Genetic risk factors (genes and syndromic associations)

2.3 Environmental risk/protective factors; GxE

3. Phenotypes

3.1 Core clinical presentation (typical)

3.2 Fetal imaging phenotypes and prenatal “suspicious signs”

3.3 Suggested HPO terms (examples)

3.4 Quality of life impact

4. Genetic / Molecular Information

4.1 Causal genes and pathogenic variants (evidence-supported in retrieved corpus)

4.2 Candidate genes / functional mechanisms

4.3 Variant class and origin

4.4 Modifier genes, epigenetics, chromosomal abnormalities

5. Environmental Information

6. Mechanism / Pathophysiology

6.1 Causal chain (integrated clinical + developmental model)

6.2 Molecular/cellular processes (evidence-linked)

6.3 Suggested ontology mappings

7. Anatomical Structures Affected

7.1 Organ/system level

8. Temporal Development

9. Inheritance and Population

9.1 Epidemiology (selected recent/representative statistics)

9.2 Sex ratio / demographics

9.3 Inheritance

10. Diagnostics

10.1 Prenatal diagnosis (real-world implementation)

10.2 Postnatal diagnosis

10.3 Differential diagnosis (not exhaustively captured in retrieved corpus)

11. Outcome / Prognosis

11.1 Natural history without intervention

11.2 Contemporary surgical outcomes and complications

11.3 Reoperation risk stratification (2024 evidence)

12. Treatment

12.1 Surgical/interventional treatment (current practice)

12.2 Supportive perioperative management

12.3 Pharmacotherapy / advanced therapeutics

12.4 Suggested MAXO terms (examples)

13. Prevention

14. Other Species / Natural Disease

15. Model Organisms

Recent developments (2023–2024 highlights)

Evidence map of key studies

Key visual evidence

Limitations of this report (data availability)