Esophageal Atresia

Congenital MONDO:0001044 Pathograph 23 Show in embeddings browser esophageal disorder congenital digestive system anomaly

Esophageal atresia is a rare congenital foregut malformation in which esophageal continuity is interrupted, most often with an associated tracheoesophageal fistula. The neonatal presentation includes inability to swallow, excessive secretions, feeding difficulty, respiratory distress, and aspiration risk, while repaired patients often have persistent gastrointestinal and respiratory morbidity.

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5
Pathophys.
15
Phenotypes
23
Pathograph
6
Genes
3
Medical Actions
5
Subtypes
4
Datasets
1
Deep Research
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Subtypes

5
Gross Type A (pure esophageal atresia)
7% in the PMID:27993359 surgical cohort
Isolated or pure esophageal atresia without an associated tracheoesophageal fistula.
Show evidence (2 references)
PMID:20425471 SUPPORT Human Clinical
"Five subtypes are described, based on the location of the atresia and the type of connection between trachea and esophagus [2]."
This review supports Gross-style anatomical subtyping by atresia location and tracheoesophageal connection.
PMID:27993359 SUPPORT Human Clinical
"The most common anatomy was proximal EA with distal TEF (n=335; 85%) followed by pure EA (n=27; 7%)."
This contemporary surgical cohort quantifies pure EA as 7% of cases.
Gross Type B (esophageal atresia with proximal fistula)
Rare; not separately quantified in the PMID:27993359 cohort abstract
Esophageal atresia with a proximal tracheoesophageal fistula and no distal fistula.
Show evidence (1 reference)
PMID:20425471 SUPPORT Human Clinical
"Five subtypes are described, based on the location of the atresia and the type of connection between trachea and esophagus [2]."
This review supports inclusion of the rare proximal-fistula anatomical subtype.
Gross Type C (esophageal atresia with distal fistula)
85% in the PMID:27993359 surgical cohort
Proximal esophageal atresia with a distal tracheoesophageal fistula; this is the dominant anatomy in contemporary EA/TEF surgical cohorts.
Show evidence (2 references)
PMID:27993359 SUPPORT Human Clinical
"The most common anatomy was proximal EA with distal TEF (n=335; 85%) followed by pure EA (n=27; 7%)."
This cohort directly identifies proximal EA with distal TEF as the most common anatomy at 85%.
PMID:31571760 SUPPORT Human Clinical
"including all cases of Gross type C EA-TEF over a period of 3 years."
This cohort explicitly uses Gross type C for EA with distal TEF.
Gross Type D (esophageal atresia with proximal and distal fistulas)
Rare; not separately quantified in the PMID:27993359 cohort abstract
Esophageal atresia with both proximal and distal tracheoesophageal fistulas.
Show evidence (1 reference)
PMID:20425471 SUPPORT Human Clinical
"Five subtypes are described, based on the location of the atresia and the type of connection between trachea and esophagus [2]."
This review supports inclusion of the rare double-fistula anatomical subtype.
Gross Type E (isolated tracheoesophageal fistula)
Rare; not separately quantified in the PMID:27993359 cohort abstract
Isolated or H-type tracheoesophageal fistula without esophageal atresia; included in the EA/TEF Gross classification but not diagnostic for esophageal atresia itself.
Show evidence (1 reference)
PMID:20425471 SUPPORT Human Clinical
"Five subtypes are described, based on the location of the atresia and the type of connection between trachea and esophagus [2]."
This review supports inclusion of the fifth Gross EA/TEF anatomical subtype.
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Pathophysiology

5
Developmental signaling defects in foregut morphogenesis
Human syndromic observations and animal models implicate disrupted foregut developmental signaling, including sonic hedgehog pathway effectors, in the susceptibility to esophageal atresia and tracheoesophageal fistula.
smoothened signaling pathway GO:0007224 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves dysregulated smoothened signaling pathway (GO:0007224). GO:0007224 is a biological process from the Gene Ontology. ↕ DYSREGULATED esophagus development GO:1903702 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves dysregulated esophagus development (GO:1903702). GO:1903702 is a biological process from the Gene Ontology. ↕ DYSREGULATED
foregut UBERON:0001041 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in foregut (UBERON:0001041). UBERON:0001041 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Incomplete embryonic foregut compartmentalization Disrupted foregut developmental signaling can impair normal partitioning of respiratory and esophageal lineages.
Clinically significant congenital heart disease EA/TEF often occurs in broader syndromic or developmental anomaly patterns that include cardiovascular malformations, although the specific intermediates vary across patients.
Show evidence (2 references)
PMID:20425471 SUPPORT Model Organism
"Studies in animal models implicate an essential role for sonic hedgehog signaling and its downstream effectors in the correct embryogenesis of the foregut."
This review summarizes model-organism evidence linking hedgehog pathway signaling to foregut embryogenesis.
PMID:32515280 SUPPORT Model Organism
"animal models have shown the involvement of multiple signaling pathways and transcription factors in the development of the esophagus and trachea."
This review supports developmental signaling and transcription-factor disruption as a mechanistic theme.
Incomplete embryonic foregut compartmentalization
The anterior foregut normally partitions into ventral respiratory and dorsal esophageal compartments; incomplete embryonic compartmentalization produces the developmental context for esophageal interruption and persistent airway communication.
esophagus development GO:1903702 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves dysregulated esophagus development (GO:1903702). GO:1903702 is a biological process from the Gene Ontology. ↕ DYSREGULATED respiratory system development GO:0060541 Gene Ontology (GO) Relation: this pathophysiological event involves this biological process This pathophysiological event involves dysregulated respiratory system development (GO:0060541). GO:0060541 is a biological process from the Gene Ontology. ↕ DYSREGULATED
foregut UBERON:0001041 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in foregut (UBERON:0001041). UBERON:0001041 is an anatomical location from the Uberon multi-species anatomy ontology. esophagus UBERON:0001043 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in esophagus (UBERON:0001043). UBERON:0001043 is an anatomical location from the Uberon multi-species anatomy ontology. trachea UBERON:0003126 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in trachea (UBERON:0003126). UBERON:0003126 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Interrupted esophageal continuity and tracheoesophageal communication Failed compartmentalization can leave esophageal discontinuity with persistent tracheoesophageal communication.
Show evidence (2 references)
PMID:31000707 SUPPORT Human Clinical
"Oesophageal atresia (EA) is a congenital abnormality of the oesophagus that is caused by incomplete embryonic compartmentalization of the foregut."
The disease primer directly identifies incomplete foregut compartmentalization as the causal developmental defect.
PMID:32515280 SUPPORT Model Organism
"Esophagus and trachea arise from a common origin, the anterior foregut tube."
This supports the shared developmental origin of the esophagus and trachea that must be partitioned correctly.
Interrupted esophageal continuity and tracheoesophageal communication
The defining anatomic outcome is interruption of esophageal continuity, with or without a persistent fistulous connection between the trachea and esophagus.
esophagus UBERON:0001043 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in esophagus (UBERON:0001043). UBERON:0001043 is an anatomical location from the Uberon multi-species anatomy ontology. trachea UBERON:0003126 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in trachea (UBERON:0003126). UBERON:0003126 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Esophageal atresia Interrupted esophageal continuity is the defining esophageal atresia malformation.
Tracheoesophageal fistula Persistent tracheoesophageal communication is represented clinically by tracheoesophageal fistula.
Absence of stomach bubble on fetal sonography Prenatal esophageal interruption can prevent normal swallowed fluid from reaching the fetal stomach, producing an absent stomach bubble on sonography.
Neonatal feeding obstruction and aspiration risk Esophageal discontinuity and fistulous airway communication produce inability to swallow, retained secretions, and aspiration risk.
Post-repair esophageal dysmotility and aerodigestive morbidity The congenital esophageal lesion and its surgical repair create the clinical context in which long-term dysmotility and aerodigestive morbidity are observed.
Show evidence (2 references)
ORPHA:1199 SUPPORT Other
"an interruption in the continuity of the esophagus, with or without persistent communication with the trachea"
Orphanet defines the anatomic lesion as interrupted esophageal continuity with possible tracheal communication.
PMID:31000707 SUPPORT Human Clinical
"EA commonly occurs with a tracheo-oesophageal fistula (TEF)."
The disease primer supports frequent association with tracheoesophageal fistula.
Neonatal feeding obstruction and aspiration risk
Because swallowed material cannot pass normally to the stomach and may communicate with the airway, neonates develop feeding difficulty, excessive secretions, vomiting or choking, respiratory distress, and aspiration complications.
Downstream
Dysphagia Inability to swallow from neonatal esophageal obstruction manifests clinically as dysphagia.
Excessive salivation Retained secretions above the obstructed esophagus produce excessive salivation.
Feeding difficulties in infancy Esophageal obstruction prevents normal oral feeds from reaching the stomach in infancy.
Aspiration Impaired swallowing and fistulous airway communication create a direct aspiration risk.
Respiratory distress Severe neonatal obstruction or airway communication can produce respiratory distress.
Failure to thrive in infancy Persistent feeding obstruction and ineffective intake can impair infant growth.
Show evidence (2 references)
ORPHA:1199 SUPPORT Other
"can lead to the inability to swallow or, in the most severe cases, respiratory distress."
Orphanet directly links the anatomic lesion to inability to swallow and respiratory distress.
PMID:27190912 SUPPORT Human Clinical
"inability to pass a nasogastric tube (NGT)"
Inability to pass a nasogastric tube reflects neonatal esophageal obstruction.
Post-repair esophageal dysmotility and aerodigestive morbidity
Even after anatomic repair, esophageal dysmotility and reflux-related complications contribute to ongoing gastrointestinal and respiratory morbidity.
esophagus UBERON:0001043 Uberon multi-species anatomy ontology (UBERON) Relation: this pathophysiological event occurs in this anatomical location This pathophysiological event occurs in esophagus (UBERON:0001043). UBERON:0001043 is an anatomical location from the Uberon multi-species anatomy ontology.
Downstream
Gastrointestinal dysmotility Post-repair esophageal motility disorder is represented in the phenotype set as gastrointestinal dysmotility.
Gastroesophageal reflux Post-repair dysmotility and altered esophageal anatomy predispose to gastroesophageal reflux.
Esophagitis Reflux-related mucosal injury after EA repair can manifest as esophagitis.
Recurrent respiratory infections Chronic aerodigestive morbidity after EA/TEF can include recurrent respiratory infections.
Restrictive ventilatory defect Restrictive pulmonary function is part of the long-term respiratory phenotype, although the cached evidence does not resolve a single patient-level intermediate mechanism.
Show evidence (2 references)
PMID:31000707 SUPPORT Human Clinical
"Oesophageal motility disorders are probably ubiquitous in patients after undergoing EA repair"
The disease primer supports esophageal dysmotility as a common post-repair mechanism of morbidity.
PMID:27579697 SUPPORT Human Clinical
"These children face gastrointestinal (GI) problems not only in early childhood but also through adolescence and adulthood."
The ESPGHAN/NASPGHAN guideline supports persistent GI morbidity across childhood and later life.
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Pathograph

Use the checkboxes to hide or show graph categories. Hover nodes for evidence and cross-linked metadata.
Pathograph: causal mechanism network for Esophageal Atresia Interactive directed graph showing how pathophysiology mechanisms, phenotypes, genetic factors and variants, experimental models, environmental triggers, and treatments relate through causal and linked edges.
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Phenotypes

15
Digestive 5
Esophageal atresia HP:0002032 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Esophageal atresia (HP:0002032). HP:0002032 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:1199 SUPPORT Other
"interruption in the continuity of the esophagus"
Orphanet directly supports esophageal atresia as the defining malformation.
PMID:31000707 SUPPORT Human Clinical
"congenital abnormality of the oesophagus"
The disease primer supports esophageal atresia as a congenital esophageal abnormality.
Tracheoesophageal fistula VERY_FREQUENT HP:0002575 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Tracheoesophageal fistula (HP:0002575). HP:0002575 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:1199 SUPPORT Other
"HP:0002575 | Tracheoesophageal fistula | Very frequent (99-80%)"
Orphanet lists tracheoesophageal fistula as very frequent in esophageal atresia.
PMID:27993359 SUPPORT Human Clinical
"The most common anatomy was proximal EA with distal TEF (n=335; 85%)"
This multi-institutional cohort supports distal TEF as the most common anatomy.
Dysphagia FREQUENT HP:0002015 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Dysphagia (HP:0002015). HP:0002015 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:1199 SUPPORT Other
"HP:0002015 | Dysphagia | Frequent (79-30%)"
Orphanet lists dysphagia as frequent in esophageal atresia.
PMID:27579697 SUPPORT Human Clinical
"investigation and management of dysphagia"
The guideline includes dysphagia among common EA complications requiring evaluation and management.
Feeding difficulties in infancy FREQUENT HP:0008872 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Feeding difficulties in infancy (HP:0008872). HP:0008872 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:1199 SUPPORT Other
"HP:0008872 | Feeding difficulties in infancy | Frequent (79-30%)"
Orphanet lists infant feeding difficulty as frequent.
PMID:27579697 SUPPORT Human Clinical
"feeding difficulties, anastomotic strictures, congenital esophageal stenosis in EA patients"
The guideline directly identifies feeding difficulties among EA complications.
Gastroesophageal reflux OCCASIONAL HP:0002020 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Gastroesophageal reflux (HP:0002020). HP:0002020 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:1199 SUPPORT Other
"HP:0002020 | Gastroesophageal reflux | Occasional (29-5%)"
Orphanet lists gastroesophageal reflux as occasional.
PMID:27579697 SUPPORT Human Clinical
"diagnosis, and treatment of gastroesophageal reflux"
The guideline specifically addresses GERD diagnosis and treatment in children with EA/TEF.
Head and Neck 1
Excessive salivation FREQUENT HP:0003781 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Excessive salivation (HP:0003781). HP:0003781 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:1199 SUPPORT Other
"HP:0003781 | Excessive salivation | Frequent (79-30%)"
Orphanet lists excessive salivation as frequent in esophageal atresia.
Immune 1
Recurrent respiratory infections FREQUENT HP:0002205 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Recurrent respiratory infections (HP:0002205). HP:0002205 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:1199 SUPPORT Other
"HP:0002205 | Recurrent respiratory infections | Frequent (79-30%)"
Orphanet lists recurrent respiratory infections as frequent.
PMID:31000707 SUPPORT Human Clinical
"long-term gastrointestinal and respiratory complications and comorbidities in patients born with EA are common"
The disease primer supports respiratory complications as common after EA.
Respiratory 3
Respiratory distress OCCASIONAL HP:0002098 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Respiratory distress (HP:0002098). HP:0002098 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:1199 SUPPORT Other
"HP:0002098 | Respiratory distress | Occasional (29-5%)"
Orphanet lists respiratory distress as occasional.
ORPHA:1199 SUPPORT Other
"in the most severe cases, respiratory distress"
The Orphanet definition directly describes respiratory distress in severe cases.
Restrictive ventilatory defect FREQUENT HP:0002091 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Restrictive ventilatory defect (HP:0002091). HP:0002091 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:1199 SUPPORT Other
"HP:0002091 | Restrictive ventilatory defect | Frequent (79-30%)"
Orphanet lists restrictive ventilatory defect as frequent.
Aspiration OCCASIONAL HP:0002835 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Aspiration (HP:0002835). HP:0002835 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:1199 SUPPORT Other
"HP:0002835 | Aspiration | Occasional (29-5%)"
Orphanet lists aspiration as an occasional phenotype.
Other 5
Clinically significant congenital heart disease FREQUENT Abnormal cardiovascular system morphology HP:0030680 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Clinically significant congenital heart disease, annotated with Abnormal cardiovascular system morphology (HP:0030680). HP:0030680 is a phenotype from the Human Phenotype Ontology.
Show evidence (3 references)
PMID:27993359 SUPPORT Human Clinical
"Clinically significant congenital heart disease (CHD) was present in 137 (35%)."
This surgical cohort directly quantifies clinically significant congenital heart disease in 35% of EA/TEF cases.
PMID:27993359 SUPPORT Human Clinical
"Mortality was 7.5% and significantly associated with CHD"
This supports the prognostic significance of congenital heart disease in the cohort.
ORPHA:1199 SUPPORT Other
"HP:0030680 | Abnormal cardiovascular system morphology | Occasional (29-5%)"
Orphanet independently lists abnormal cardiovascular morphology among associated EA phenotypes.
Failure to thrive in infancy FREQUENT HP:0001531 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Failure to thrive in infancy (HP:0001531). HP:0001531 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:1199 SUPPORT Other
"HP:0001531 | Failure to thrive in infancy | Frequent (79-30%)"
Orphanet lists failure to thrive in infancy as frequent.
Gastrointestinal dysmotility FREQUENT HP:0002579 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Gastrointestinal dysmotility (HP:0002579). HP:0002579 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:1199 SUPPORT Other
"HP:0002579 | Gastrointestinal dysmotility | Frequent (79-30%)"
Orphanet lists gastrointestinal dysmotility as frequent.
PMID:31000707 SUPPORT Human Clinical
"Oesophageal motility disorders are probably ubiquitous in patients after undergoing EA repair"
The disease primer supports post-repair esophageal dysmotility as very common.
Absence of stomach bubble on fetal sonography FREQUENT HP:0010963 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Absence of stomach bubble on fetal sonography (HP:0010963). HP:0010963 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
ORPHA:1199 SUPPORT Other
"HP:0010963 | Absence of stomach bubble on fetal sonography | Frequent (79-30%)"
Orphanet lists absent stomach bubble on fetal sonography as frequent.
PMID:22247246 SUPPORT Human Clinical
"Prenatal detection rates varied by registry from >50% of cases to <10% of cases."
Registry data support prenatal detection as part of the clinical diagnostic course.
Esophagitis FREQUENT HP:0100633 Human Phenotype Ontology (HP) Relation: this clinical feature is this phenotype This clinical feature is Esophagitis (HP:0100633). HP:0100633 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
ORPHA:1199 SUPPORT Other
"HP:0100633 | Esophagitis | Frequent (79-30%)"
Orphanet lists esophagitis as frequent.
🧬

Genetic Associations

6
Syndromic and chromosomal associations (Syndromic and chromosomal association)
Show evidence (3 references)
PMID:31000707 SUPPORT Human Clinical
"Associated birth defects or anomalies, such as VACTERL association, trisomy 18 or 21 and CHARGE syndrome, occur in the majority of patients born with EA."
The disease primer supports common syndromic and chromosomal associations in EA.
PMID:20425471 SUPPORT Human Clinical
"In 6% to 10% of patients a defined genetic syndrome can be diagnosed"
This review quantifies defined genetic syndrome diagnoses among EA/TEF patients.
PMID:20425471 SUPPORT Human Clinical
"Many well-known chromosomal aberrations are observed in EA/TEF patients, such as Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), and Patau syndrome (trisomy 13)"
This review documents chromosomal trisomies and other chromosomal aberrations in EA/TEF patients.
VACTERL association (Syndromic association)
Show evidence (1 reference)
PMID:20425471 SUPPORT Human Clinical
"EA/TEF is a component of the VACTERL association, which includes vertebral, anal, cardiovascular, tracheoesophageal, renal, and limb anomalies, and is seen in 10% to 30% of EA/TEF patients [1, 19]."
This review directly supports VACTERL association as a frequent associated context in EA/TEF.
CHD7-associated CHARGE syndrome (Syndromic association)
Gene: CHD7 hgnc:20626 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is CHD7 (hgnc:20626). hgnc:20626 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: SUSCEPTIBILITY
Show evidence (2 references)
PMID:20425471 SUPPORT Human Clinical
"About 10% of patients with CHARGE syndrome display EA/TEF."
This review supports EA/TEF as a feature in a subset of CHARGE syndrome patients.
PMID:20425471 SUPPORT Human Clinical
"caused by mutations in the chromodomain helicase DNA-binding (CHD7) gene"
This supports CHD7 as the gene underlying the relevant syndromic association.
MYCN-associated Feingold syndrome (Syndromic association)
Gene: MYCN hgnc:7559 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is MYCN (hgnc:7559). hgnc:7559 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: SUSCEPTIBILITY
Show evidence (2 references)
PMID:20425471 SUPPORT Human Clinical
"Feingold syndrome is caused by germline mutations in, or deletions of, the MYCN gene on chromosome 2p24.1."
This review identifies MYCN as the causal gene for the Feingold syndrome association.
PMID:20425471 SUPPORT Human Clinical
"About 30% to 40% of patients diagnosed with Feingold syndrome have EA/TEF [25]."
This review directly supports EA/TEF enrichment in Feingold syndrome.
SOX2-associated anophthalmia-esophageal-genital syndrome (Syndromic association)
Gene: SOX2 hgnc:11195 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is SOX2 (hgnc:11195). hgnc:11195 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: SUSCEPTIBILITY
Show evidence (1 reference)
PMID:20425471 SUPPORT Human Clinical
"Deletions and mutations of the SOX2 gene are causative for the phenotype of clinical anophthalmia/optic nerve hypoplasia, esophageal atresia, and/or genital anomalies in the AEG syndrome [28]."
This review directly links SOX2 alterations to a syndromic phenotype including esophageal atresia.
FOXF1 and sonic hedgehog pathway developmental susceptibility (Developmental susceptibility)
Gene: FOXF1 hgnc:3809 HUGO Gene Nomenclature Committee (hgnc) Relation: this disease-associated gene is this gene This disease-associated gene is FOXF1 (hgnc:3809). hgnc:3809 is a gene from the HUGO Gene Nomenclature Committee. relationship_type: SUSCEPTIBILITY
Show evidence (2 references)
PMID:20425471 SUPPORT Human Clinical
"mutations in the FOXF1 gene, in patients with alveolar capillary dysplasia combined with VACTERL-associated anomalies, including EA/TEF [24••]."
This review links FOXF1-region alterations to human VACTERL-associated anomalies including EA/TEF.
PMID:20425471 SUPPORT Model Organism
"Genes of developmental pathways are involved, including vitamin A effectors (Rarα, Rarβ), effectors of the sonic hedgehog (SHH) pathway (Shh, Gli2, Gli3, Foxf1)"
This supports FOXF1 and SHH-pathway effectors as model-organism developmental susceptibility genes for tracheoesophageal anomalies.
💊

Medical Actions

3
Primary surgical repair with tracheoesophageal fistula ligation
Action: surgical repairNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is surgical repair, annotated with Surgical Procedure (NCIT:C15329). NCIT:C15329 is a clinical intervention from the NCI Thesaurus. Ontology label: Surgical Procedure NCIT:C15329
Standard neonatal management restores esophageal continuity and ligates or divides a tracheoesophageal fistula when present.
Target Phenotypes: Esophageal atresia HP:0002032 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Esophageal atresia (HP:0002032). HP:0002032 is a phenotype from the Human Phenotype Ontology. Tracheoesophageal fistula HP:0002575 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Tracheoesophageal fistula (HP:0002575). HP:0002575 is a phenotype from the Human Phenotype Ontology.
Show evidence (2 references)
PMID:31000707 SUPPORT Human Clinical
"EA is treated surgically to restore the oesophageal interruption and, if present, ligate and divide the TEF."
The disease primer directly states the surgical repair goals.
PMID:27993359 SUPPORT Human Clinical
"surgical repair of their defect defined as esophageal reconstruction with or without ligation of TEF"
The surgical cohort defines repair as esophageal reconstruction with or without TEF ligation.
Gastroesophageal reflux treatment
Action: PharmacotherapyNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is Pharmacotherapy (NCIT:C15986). NCIT:C15986 is a clinical intervention from the NCI Thesaurus. NCIT:C15986
Long-term care includes treatment of gastroesophageal reflux after EA/TEF repair.
Target Phenotypes: Gastroesophageal reflux HP:0002020 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Gastroesophageal reflux (HP:0002020). HP:0002020 is a phenotype from the Human Phenotype Ontology. Dysphagia HP:0002015 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Dysphagia (HP:0002015). HP:0002015 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:27579697 SUPPORT Human Clinical
"Questions on the diagnosis, and treatment of gastroesophageal reflux"
The guideline explicitly covers treatment of GERD in children with EA/TEF.
Balloon dilatation for post-repair anastomotic strictures
Action: endoscopic procedureNCI Thesaurus (NCIT) Relation: this treatment is this clinical intervention This treatment is endoscopic procedure (NCIT:C16546). NCIT:C16546 is a clinical intervention from the NCI Thesaurus. Ontology label: Endoscopic Procedure NCIT:C16546
Anastomotic strictures after esophageal atresia repair are often managed with fluoroscopic or endoscopic balloon dilatation.
Target Phenotypes: Dysphagia HP:0002015 Human Phenotype Ontology (HP) Relation: this treatment targets this phenotype This treatment targets Dysphagia (HP:0002015). HP:0002015 is a phenotype from the Human Phenotype Ontology.
Show evidence (1 reference)
PMID:23877544 SUPPORT Human Clinical
"These strictures are often treated by balloon dilatation (BD) and currently balloon dilatation (fluoroscopic or endoscopic) is the preferred primary treatment method."
This systematic review directly supports balloon dilatation for anastomotic strictures after EA repair.
🔬

Diagnosis

2
Nasogastric tube passage with chest radiograph
In the newborn period, inability to pass a nasogastric tube and radiographic localization of the arrested tube support diagnosis and can help estimate esophageal gap length before repair.
radiograph imaging procedure NCIT:C38101 NCI Thesaurus (NCIT)
Results: Arrested nasogastric tube in the upper esophageal pouch; esophageal gap length estimate.
Show evidence (2 references)
PMID:31571760 SUPPORT Human Clinical
"Plain radiograph including chest and abdomen with nasogastric tube no 8 Fr in the upper esophagus were taken for all patients to confirm the diagnosis"
This prospective cohort directly supports radiography with a nasogastric tube for diagnosis.
PMID:27190912 SUPPORT Human Clinical
"confirmed by contrast study showing blind upper oesophageal pouch."
This case report supports imaging confirmation of a blind upper esophageal pouch.
Post-repair motility and reflux assessment
High-resolution impedance manometry and pH-multichannel intraluminal impedance testing can characterize post-repair dysmotility and reflux burden.
clinical assessment NCIT:C124351 NCI Thesaurus (NCIT)
Results: Esophageal motility pattern, reflux burden, and symptom correlation.
Show evidence (1 reference)
PMID:31000707 SUPPORT Human Clinical
"including high-resolution impedance manometry, pH-multichannel intraluminal impedance testing"
The disease primer identifies manometry and pH-impedance testing as clinical tools for post-repair morbidity.
📈

Progression

2
Neonatal recognition
Esophageal atresia is present at birth and is commonly recognized in the newborn period because of failure to pass a nasogastric tube, excessive secretions, feeding difficulty, and respiratory symptoms.
Show evidence (2 references)
ORPHA:1199 SUPPORT Other
"Age of onset: Neonatal"
Orphanet lists neonatal onset for esophageal atresia.
PMID:27190912 SUPPORT Human Clinical
"commonly diagnosed in the newborn period by inability to pass a nasogastric tube"
This case report abstract summarizes the classic neonatal diagnostic presentation.
Post-repair long-term morbidity
Survival after modern repair is high, but gastrointestinal dysmotility, reflux, strictures, feeding difficulty, and respiratory complications often require long-term follow-up.
Show evidence (1 reference)
PMID:31000707 SUPPORT Human Clinical
"long-term gastrointestinal and respiratory complications and comorbidities in patients born with EA are common"
The disease primer explicitly supports persistent long-term GI and respiratory morbidity after EA.
📊

Prevalence

2
European congenital anomaly registries
Birth Prevalence 24.3 per 100,000 1–9 per 10,000
EUROCAT surveillance across 23 European regions found an overall prevalence of 2.43 cases per 10,000 births between 1987 and 2006.
Show evidence (1 reference)
PMID:22247246 SUPPORT Human Clinical
"The overall prevalence was 2.43 cases per 10 000 births"
This population-based registry study directly reports the European prevalence estimate.
Europe
Birth Prevalence 10.0–50.0 per 100,000 1–9 per 10,000
Orphanet classifies European point prevalence and prevalence at birth in the 1-5 per 10,000 range.
Show evidence (1 reference)
ORPHA:1199 SUPPORT Other
"1-5 / 10 000 | Europe | Prevalence at birth | PMID:22247246,REG"
Orphanet provides a structured European birth-prevalence estimate for esophageal atresia.
📊

Related Datasets

4
Investigating the mechanisms by which SMAD6 mutations cause tracheoesophageal birth defects geo:GSE305960
Esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) are tracheoesophageal (TE) birth defects which affect 1 in 3000 live births in the United States. EA occurs when the esophagus fails to form a continuous tube from the oral cavity to the stomach and TEF occurs when there is an abnormal connection between the trachea and esophagus. The etiology of EA/TEF arises when the common foregut tube fails to properly separate into the esophagus and respiratory tract during early embryogenesis. This process is essential for proper organ function and involves complex molecular and morphological processes.
human BULK RNA SEQ n=54
Identified by GEO DataSets index search for Esophageal Atresia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
Chromosomal abnormalities and pregnancy outcomes for fetuses with gastrointestinal tract obstructions geo:GSE203126
Fetal gastrointestinal tract obstructions (GITO) is the most frequently encountered gastrointestinal defects in prenatal. This study aimed to investigate the genetic disorders and pregnancy outcomes of fetal GITO. We reviewed data from 70 pregnancies who were referred for invasive prenatal testing due to fetal GITO. According to the levels of obstruction, they were classified into esophageal atresia/stenosis, duodenal atresia/stenosis, jejunal or ileal atresia/stenosis, and anal atresia. Traditional karyotyping was performed on all 70 pregnancies, and chromosomal microarray analysis (CMA) was performed on 32 of them in parallel.
human n=32
PMID:35783302
Identified by GEO DataSets index search for Esophageal Atresia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
Tracheoesophageal fistula characterisation geo:GSE148247
Esophageal atresia and tracheoesophageal fistula (EA/TEF) are relatively frequently occurring foregut malformations with a largely unknown etiology. EA/TEF is thought to have a strong genetic component and several genes have been proven to be involved in syndromic EA/TEF. However, it is not clear which biological processes or gene networks are disturbed. To gain more insight in the origin of the TEF, we aimed to examine and describe TEF composition using a combination of whole-genome transcription profiling and (immuno-) histochemical stainings. We hypothesized that such characterization of human TEFs provides insight in the molecular and mechanistic etiology of EA/TEF.
human BULK RNA SEQ n=31
PMID:33201890
Identified by GEO DataSets index search for Esophageal Atresia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
Kids First: Genomic Analysis of Esophageal Atresia and Tracheoesophageal Fistulas and Associated Congenital Anomalies dbgap:phs002161
The Gabriella Miller Kids First Pediatric Research Program (Kids First) is a trans-NIH effort initiated in response to the 2014 Gabriella Miller Kids First Research Act and supported by the NIH Common Fund. This program focuses on gene discovery in pediatric cancers and structural birth defects and the development of the Gabriella Miller Kids First Pediatric Data Resource (Kids First Data Resource). All of the WGS and phenotypic data from this study are accessible through dbGaP and kidsfirstdrc.org , where ot
Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Esophageal Atresia"). Retrieved 2026-08-02.
{ }

Source YAML

click to show 
name: Esophageal Atresia
creation_date: "2026-05-07T23:23:53Z"
description: >-
  Esophageal atresia is a rare congenital foregut malformation in which
  esophageal continuity is interrupted, most often with an associated
  tracheoesophageal fistula. The neonatal presentation includes inability to
  swallow, excessive secretions, feeding difficulty, respiratory distress, and
  aspiration risk, while repaired patients often have persistent gastrointestinal
  and respiratory morbidity.
category: Congenital
disease_term:
  preferred_term: esophageal atresia
  term:
    id: MONDO:0001044
    label: esophageal atresia
parents:
- esophageal disorder
- congenital digestive system anomaly
synonyms:
- Congenital esophageal atresia
- EA/TEF
- Esophageal atresia with or without tracheoesophageal fistula
- Oesophageal atresia
has_subtypes:
- name: Gross Type A
  display_name: Gross Type A (pure esophageal atresia)
  description: >-
    Isolated or pure esophageal atresia without an associated
    tracheoesophageal fistula.
  subtype_frequency: 7% in the PMID:27993359 surgical cohort
  classification: Gross anatomical classification
  evidence:
  - reference: PMID:20425471
    reference_title: "Etiology of esophageal atresia and tracheoesophageal fistula: \"mind the gap\"."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Five subtypes are described, based on the location of the atresia and the type of connection between trachea and esophagus [2]."
    explanation: This review supports Gross-style anatomical subtyping by atresia location and tracheoesophageal connection.
  - reference: PMID:27993359
    reference_title: Perioperative management and outcomes of esophageal atresia and tracheoesophageal fistula.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The most common anatomy was proximal EA with distal TEF (n=335; 85%) followed by pure EA (n=27; 7%)."
    explanation: This contemporary surgical cohort quantifies pure EA as 7% of cases.
- name: Gross Type B
  display_name: Gross Type B (esophageal atresia with proximal fistula)
  description: >-
    Esophageal atresia with a proximal tracheoesophageal fistula and no distal
    fistula.
  subtype_frequency: Rare; not separately quantified in the PMID:27993359 cohort abstract
  classification: Gross anatomical classification
  evidence:
  - reference: PMID:20425471
    reference_title: "Etiology of esophageal atresia and tracheoesophageal fistula: \"mind the gap\"."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Five subtypes are described, based on the location of the atresia and the type of connection between trachea and esophagus [2]."
    explanation: This review supports inclusion of the rare proximal-fistula anatomical subtype.
- name: Gross Type C
  display_name: Gross Type C (esophageal atresia with distal fistula)
  description: >-
    Proximal esophageal atresia with a distal tracheoesophageal fistula; this is
    the dominant anatomy in contemporary EA/TEF surgical cohorts.
  subtype_frequency: 85% in the PMID:27993359 surgical cohort
  classification: Gross anatomical classification
  evidence:
  - reference: PMID:27993359
    reference_title: Perioperative management and outcomes of esophageal atresia and tracheoesophageal fistula.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The most common anatomy was proximal EA with distal TEF (n=335; 85%) followed by pure EA (n=27; 7%)."
    explanation: This cohort directly identifies proximal EA with distal TEF as the most common anatomy at 85%.
  - reference: PMID:31571760
    reference_title: Prediction of Gap Length by Plain Radiograph of Chest with Nasogastric Tube in the Upper Esophagus in Patients with Esophageal Atresia and Distal Tracheoesophageal Fistula.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "including all cases of Gross type C EA-TEF over a period of 3 years."
    explanation: This cohort explicitly uses Gross type C for EA with distal TEF.
- name: Gross Type D
  display_name: Gross Type D (esophageal atresia with proximal and distal fistulas)
  description: >-
    Esophageal atresia with both proximal and distal tracheoesophageal fistulas.
  subtype_frequency: Rare; not separately quantified in the PMID:27993359 cohort abstract
  classification: Gross anatomical classification
  evidence:
  - reference: PMID:20425471
    reference_title: "Etiology of esophageal atresia and tracheoesophageal fistula: \"mind the gap\"."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Five subtypes are described, based on the location of the atresia and the type of connection between trachea and esophagus [2]."
    explanation: This review supports inclusion of the rare double-fistula anatomical subtype.
- name: Gross Type E
  display_name: Gross Type E (isolated tracheoesophageal fistula)
  description: >-
    Isolated or H-type tracheoesophageal fistula without esophageal atresia;
    included in the EA/TEF Gross classification but not diagnostic for
    esophageal atresia itself.
  subtype_frequency: Rare; not separately quantified in the PMID:27993359 cohort abstract
  classification: Gross anatomical classification
  evidence:
  - reference: PMID:20425471
    reference_title: "Etiology of esophageal atresia and tracheoesophageal fistula: \"mind the gap\"."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Five subtypes are described, based on the location of the atresia and the type of connection between trachea and esophagus [2]."
    explanation: This review supports inclusion of the fifth Gross EA/TEF anatomical subtype.
prevalence:
- population: European congenital anomaly registries
  measure_type: BIRTH_PREVALENCE
  prevalence_class: BAND_1_5_PER_10000
  rate_per_100000: 24.3
  percentage: 2.43 per 10,000 births
  notes: >-
    EUROCAT surveillance across 23 European regions found an overall prevalence
    of 2.43 cases per 10,000 births between 1987 and 2006.
  evidence:
  - reference: PMID:22247246
    reference_title: "Oesophageal atresia: prevalence, prenatal diagnosis and associated anomalies in 23 European regions."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The overall prevalence was 2.43 cases per 10 000 births"
    explanation: This population-based registry study directly reports the European prevalence estimate.
- population: Europe
  measure_type: BIRTH_PREVALENCE
  prevalence_class: BAND_1_5_PER_10000
  rate_low: 10.0
  rate_high: 50.0
  percentage: 1-5 per 10,000
  notes: Orphanet classifies European point prevalence and prevalence at birth in the 1-5 per 10,000 range.
  evidence:
  - reference: ORPHA:1199
    reference_title: "Esophageal atresia"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "1-5 / 10 000 | Europe | Prevalence at birth | PMID:22247246,REG"
    explanation: Orphanet provides a structured European birth-prevalence estimate for esophageal atresia.
progression:
- phase: Neonatal recognition
  notes: >-
    Esophageal atresia is present at birth and is commonly recognized in the
    newborn period because of failure to pass a nasogastric tube, excessive
    secretions, feeding difficulty, and respiratory symptoms.
  evidence:
  - reference: ORPHA:1199
    reference_title: "Esophageal atresia"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "Age of onset: Neonatal"
    explanation: Orphanet lists neonatal onset for esophageal atresia.
  - reference: PMID:27190912
    reference_title: Appearances are Deceptive - Passing a Nasogastric Tube does Not Always Rule Out Oesophageal Atresia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "commonly diagnosed in the newborn period by inability to pass a nasogastric tube"
    explanation: This case report abstract summarizes the classic neonatal diagnostic presentation.
- phase: Post-repair long-term morbidity
  notes: >-
    Survival after modern repair is high, but gastrointestinal dysmotility,
    reflux, strictures, feeding difficulty, and respiratory complications often
    require long-term follow-up.
  evidence:
  - reference: PMID:31000707
    reference_title: Oesophageal atresia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "long-term gastrointestinal and respiratory complications and comorbidities in patients born with EA are common"
    explanation: The disease primer explicitly supports persistent long-term GI and respiratory morbidity after EA.
pathophysiology:
- name: Developmental signaling defects in foregut morphogenesis
  description: >-
    Human syndromic observations and animal models implicate disrupted foregut
    developmental signaling, including sonic hedgehog pathway effectors, in the
    susceptibility to esophageal atresia and tracheoesophageal fistula.
  locations:
  - preferred_term: foregut
    term:
      id: UBERON:0001041
      label: foregut
  biological_processes:
  - preferred_term: smoothened signaling pathway
    term:
      id: GO:0007224
      label: smoothened signaling pathway
    modifier: DYSREGULATED
  - preferred_term: esophagus development
    term:
      id: GO:1903702
      label: esophagus development
    modifier: DYSREGULATED
  evidence:
  - reference: PMID:20425471
    reference_title: "Etiology of esophageal atresia and tracheoesophageal fistula: \"mind the gap\"."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Studies in animal models implicate an essential role for sonic hedgehog signaling and its downstream effectors in the correct embryogenesis of the foregut."
    explanation: This review summarizes model-organism evidence linking hedgehog pathway signaling to foregut embryogenesis.
  - reference: PMID:32515280
    reference_title: Genetic Mouse Models and Induced Pluripotent Stem Cells for Studying Tracheal-Esophageal Separation and Esophageal Development.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "animal models have shown the involvement of multiple signaling pathways and transcription factors in the development of the esophagus and trachea."
    explanation: This review supports developmental signaling and transcription-factor disruption as a mechanistic theme.
  downstream:
  - target: Incomplete embryonic foregut compartmentalization
    description: Disrupted foregut developmental signaling can impair normal partitioning of respiratory and esophageal lineages.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
  - target: Clinically significant congenital heart disease
    description: >-
      EA/TEF often occurs in broader syndromic or developmental anomaly
      patterns that include cardiovascular malformations, although the specific
      intermediates vary across patients.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: PMID:20425471
      reference_title: "Etiology of esophageal atresia and tracheoesophageal fistula: \"mind the gap\"."
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "EA/TEF is a component of the VACTERL association, which includes vertebral, anal, cardiovascular, tracheoesophageal, renal, and limb anomalies, and is seen in 10% to 30% of EA/TEF patients [1, 19]."
      explanation: >-
        VACTERL association provides an evidence-backed developmental context
        linking EA/TEF with cardiovascular malformations, while leaving the
        patient-specific intermediates unresolved.
    - reference: PMID:27993359
      reference_title: Perioperative management and outcomes of esophageal atresia and tracheoesophageal fistula.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Clinically significant congenital heart disease (CHD) was present in 137 (35%)."
      explanation: The surgical cohort quantifies clinically significant congenital heart disease in EA/TEF patients.
- name: Incomplete embryonic foregut compartmentalization
  description: >-
    The anterior foregut normally partitions into ventral respiratory and dorsal
    esophageal compartments; incomplete embryonic compartmentalization produces
    the developmental context for esophageal interruption and persistent airway
    communication.
  locations:
  - preferred_term: foregut
    term:
      id: UBERON:0001041
      label: foregut
  - preferred_term: esophagus
    term:
      id: UBERON:0001043
      label: esophagus
  - preferred_term: trachea
    term:
      id: UBERON:0003126
      label: trachea
  biological_processes:
  - preferred_term: esophagus development
    term:
      id: GO:1903702
      label: esophagus development
    modifier: DYSREGULATED
  - preferred_term: respiratory system development
    term:
      id: GO:0060541
      label: respiratory system development
    modifier: DYSREGULATED
  evidence:
  - reference: PMID:31000707
    reference_title: Oesophageal atresia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Oesophageal atresia (EA) is a congenital abnormality of the oesophagus that is caused by incomplete embryonic compartmentalization of the foregut."
    explanation: The disease primer directly identifies incomplete foregut compartmentalization as the causal developmental defect.
  - reference: PMID:32515280
    reference_title: Genetic Mouse Models and Induced Pluripotent Stem Cells for Studying Tracheal-Esophageal Separation and Esophageal Development.
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Esophagus and trachea arise from a common origin, the anterior foregut tube."
    explanation: This supports the shared developmental origin of the esophagus and trachea that must be partitioned correctly.
  downstream:
  - target: Interrupted esophageal continuity and tracheoesophageal communication
    description: Failed compartmentalization can leave esophageal discontinuity with persistent tracheoesophageal communication.
    causal_link_type: DIRECT
- name: Interrupted esophageal continuity and tracheoesophageal communication
  description: >-
    The defining anatomic outcome is interruption of esophageal continuity, with
    or without a persistent fistulous connection between the trachea and
    esophagus.
  locations:
  - preferred_term: esophagus
    term:
      id: UBERON:0001043
      label: esophagus
  - preferred_term: trachea
    term:
      id: UBERON:0003126
      label: trachea
  evidence:
  - reference: ORPHA:1199
    reference_title: "Esophageal atresia"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "an interruption in the continuity of the esophagus, with or without persistent communication with the trachea"
    explanation: Orphanet defines the anatomic lesion as interrupted esophageal continuity with possible tracheal communication.
  - reference: PMID:31000707
    reference_title: Oesophageal atresia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "EA commonly occurs with a tracheo-oesophageal fistula (TEF)."
    explanation: The disease primer supports frequent association with tracheoesophageal fistula.
  downstream:
  - target: Esophageal atresia
    description: Interrupted esophageal continuity is the defining esophageal atresia malformation.
    causal_link_type: DIRECT
    evidence:
    - reference: ORPHA:1199
      reference_title: "Esophageal atresia"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "interruption in the continuity of the esophagus"
      explanation: Orphanet directly supports interrupted esophageal continuity as esophageal atresia.
  - target: Tracheoesophageal fistula
    description: Persistent tracheoesophageal communication is represented clinically by tracheoesophageal fistula.
    causal_link_type: DIRECT
    evidence:
    - reference: ORPHA:1199
      reference_title: "Esophageal atresia"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "HP:0002575 | Tracheoesophageal fistula | Very frequent (99-80%)"
      explanation: Orphanet lists tracheoesophageal fistula as very frequent in esophageal atresia.
  - target: Absence of stomach bubble on fetal sonography
    description: >-
      Prenatal esophageal interruption can prevent normal swallowed fluid from
      reaching the fetal stomach, producing an absent stomach bubble on
      sonography.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Impaired fetal swallowing transit to the stomach.
    evidence:
    - reference: ORPHA:1199
      reference_title: "Esophageal atresia"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "HP:0010963 | Absence of stomach bubble on fetal sonography | Frequent (79-30%)"
      explanation: Orphanet lists absent fetal stomach bubble as a frequent prenatal finding in esophageal atresia.
  - target: Neonatal feeding obstruction and aspiration risk
    description: Esophageal discontinuity and fistulous airway communication produce inability to swallow, retained secretions, and aspiration risk.
    causal_link_type: DIRECT
  - target: Post-repair esophageal dysmotility and aerodigestive morbidity
    description: The congenital esophageal lesion and its surgical repair create the clinical context in which long-term dysmotility and aerodigestive morbidity are observed.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
- name: Neonatal feeding obstruction and aspiration risk
  description: >-
    Because swallowed material cannot pass normally to the stomach and may
    communicate with the airway, neonates develop feeding difficulty, excessive
    secretions, vomiting or choking, respiratory distress, and aspiration
    complications.
  evidence:
  - reference: ORPHA:1199
    reference_title: "Esophageal atresia"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "can lead to the inability to swallow or, in the most severe cases, respiratory distress."
    explanation: Orphanet directly links the anatomic lesion to inability to swallow and respiratory distress.
  - reference: PMID:27190912
    reference_title: Appearances are Deceptive - Passing a Nasogastric Tube does Not Always Rule Out Oesophageal Atresia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "inability to pass a nasogastric tube (NGT)"
    explanation: Inability to pass a nasogastric tube reflects neonatal esophageal obstruction.
  downstream:
  - target: Dysphagia
    description: Inability to swallow from neonatal esophageal obstruction manifests clinically as dysphagia.
    causal_link_type: DIRECT
    evidence:
    - reference: ORPHA:1199
      reference_title: "Esophageal atresia"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "can lead to the inability to swallow or, in the most severe cases, respiratory distress."
      explanation: Orphanet directly describes inability to swallow as a clinical consequence of the lesion.
  - target: Excessive salivation
    description: Retained secretions above the obstructed esophagus produce excessive salivation.
    causal_link_type: DIRECT
    evidence:
    - reference: ORPHA:1199
      reference_title: "Esophageal atresia"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "HP:0003781 | Excessive salivation | Frequent (79-30%)"
      explanation: Orphanet lists excessive salivation as frequent in esophageal atresia.
  - target: Feeding difficulties in infancy
    description: Esophageal obstruction prevents normal oral feeds from reaching the stomach in infancy.
    causal_link_type: DIRECT
    evidence:
    - reference: ORPHA:1199
      reference_title: "Esophageal atresia"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "HP:0008872 | Feeding difficulties in infancy | Frequent (79-30%)"
      explanation: Orphanet lists infant feeding difficulty as frequent in esophageal atresia.
    - reference: PMID:27579697
      reference_title: ESPGHAN-NASPGHAN Guidelines for the Evaluation and Treatment of Gastrointestinal and Nutritional Complications in Children With Esophageal Atresia-Tracheoesophageal Fistula.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "feeding difficulties, anastomotic strictures, congenital esophageal stenosis in EA patients"
      explanation: The guideline identifies feeding difficulties among EA complications.
  - target: Aspiration
    description: Impaired swallowing and fistulous airway communication create a direct aspiration risk.
    causal_link_type: DIRECT
    evidence:
    - reference: ORPHA:1199
      reference_title: "Esophageal atresia"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "HP:0002835 | Aspiration | Occasional (29-5%)"
      explanation: Orphanet lists aspiration as an occasional phenotype in esophageal atresia.
  - target: Respiratory distress
    description: Severe neonatal obstruction or airway communication can produce respiratory distress.
    causal_link_type: DIRECT
    evidence:
    - reference: ORPHA:1199
      reference_title: "Esophageal atresia"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "in the most severe cases, respiratory distress"
      explanation: The Orphanet definition directly describes respiratory distress in severe cases.
  - target: Failure to thrive in infancy
    description: Persistent feeding obstruction and ineffective intake can impair infant growth.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Feeding difficulty and inadequate nutritional intake.
    evidence:
    - reference: ORPHA:1199
      reference_title: "Esophageal atresia"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "HP:0001531 | Failure to thrive in infancy | Frequent (79-30%)"
      explanation: Orphanet lists failure to thrive in infancy as frequent in esophageal atresia.
- name: Post-repair esophageal dysmotility and aerodigestive morbidity
  description: >-
    Even after anatomic repair, esophageal dysmotility and reflux-related
    complications contribute to ongoing gastrointestinal and respiratory
    morbidity.
  locations:
  - preferred_term: esophagus
    term:
      id: UBERON:0001043
      label: esophagus
  evidence:
  - reference: PMID:31000707
    reference_title: Oesophageal atresia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Oesophageal motility disorders are probably ubiquitous in patients after undergoing EA repair"
    explanation: The disease primer supports esophageal dysmotility as a common post-repair mechanism of morbidity.
  - reference: PMID:27579697
    reference_title: ESPGHAN-NASPGHAN Guidelines for the Evaluation and Treatment of Gastrointestinal and Nutritional Complications in Children With Esophageal Atresia-Tracheoesophageal Fistula.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "These children face gastrointestinal (GI) problems not only in early childhood but also through adolescence and adulthood."
    explanation: The ESPGHAN/NASPGHAN guideline supports persistent GI morbidity across childhood and later life.
  downstream:
  - target: Gastrointestinal dysmotility
    description: Post-repair esophageal motility disorder is represented in the phenotype set as gastrointestinal dysmotility.
    causal_link_type: DIRECT
    evidence:
    - reference: PMID:31000707
      reference_title: Oesophageal atresia.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "Oesophageal motility disorders are probably ubiquitous in patients after undergoing EA repair"
      explanation: The disease primer directly supports post-repair esophageal dysmotility.
  - target: Gastroesophageal reflux
    description: Post-repair dysmotility and altered esophageal anatomy predispose to gastroesophageal reflux.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Post-repair esophageal dysmotility and altered clearance.
    evidence:
    - reference: PMID:27579697
      reference_title: ESPGHAN-NASPGHAN Guidelines for the Evaluation and Treatment of Gastrointestinal and Nutritional Complications in Children With Esophageal Atresia-Tracheoesophageal Fistula.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "diagnosis, and treatment of gastroesophageal reflux"
      explanation: The guideline specifically addresses GERD in children with EA/TEF.
  - target: Esophagitis
    description: Reflux-related mucosal injury after EA repair can manifest as esophagitis.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Gastroesophageal reflux.
    evidence:
    - reference: ORPHA:1199
      reference_title: "Esophageal atresia"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "HP:0100633 | Esophagitis | Frequent (79-30%)"
      explanation: Orphanet lists esophagitis as frequent in esophageal atresia.
  - target: Recurrent respiratory infections
    description: Chronic aerodigestive morbidity after EA/TEF can include recurrent respiratory infections.
    causal_link_type: INDIRECT_KNOWN_INTERMEDIATES
    intermediate_mechanisms:
    - Aspiration and reflux-related airway morbidity.
    evidence:
    - reference: ORPHA:1199
      reference_title: "Esophageal atresia"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "HP:0002205 | Recurrent respiratory infections | Frequent (79-30%)"
      explanation: Orphanet lists recurrent respiratory infections as frequent.
    - reference: PMID:31000707
      reference_title: Oesophageal atresia.
      supports: SUPPORT
      evidence_source: HUMAN_CLINICAL
      snippet: "long-term gastrointestinal and respiratory complications and comorbidities in patients born with EA are common"
      explanation: The disease primer supports common long-term respiratory morbidity after EA.
  - target: Restrictive ventilatory defect
    description: >-
      Restrictive pulmonary function is part of the long-term respiratory
      phenotype, although the cached evidence does not resolve a single
      patient-level intermediate mechanism.
    causal_link_type: INDIRECT_UNKNOWN_INTERMEDIATES
    evidence:
    - reference: ORPHA:1199
      reference_title: "Esophageal atresia"
      supports: SUPPORT
      evidence_source: OTHER
      snippet: "HP:0002091 | Restrictive ventilatory defect | Frequent (79-30%)"
      explanation: Orphanet lists restrictive ventilatory defect as frequent in esophageal atresia.
phenotypes:
- category: Gastrointestinal
  name: Esophageal atresia
  diagnostic: true
  description: Interruption of esophageal continuity is the defining malformation.
  phenotype_term:
    preferred_term: Esophageal atresia
    term:
      id: HP:0002032
      label: Esophageal atresia
  evidence:
  - reference: ORPHA:1199
    reference_title: "Esophageal atresia"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "interruption in the continuity of the esophagus"
    explanation: Orphanet directly supports esophageal atresia as the defining malformation.
  - reference: PMID:31000707
    reference_title: Oesophageal atresia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "congenital abnormality of the oesophagus"
    explanation: The disease primer supports esophageal atresia as a congenital esophageal abnormality.
- category: Respiratory
  name: Tracheoesophageal fistula
  frequency: VERY_FREQUENT
  description: Persistent communication between the esophagus and trachea is very frequently associated with esophageal atresia.
  phenotype_term:
    preferred_term: Tracheoesophageal fistula
    term:
      id: HP:0002575
      label: Tracheoesophageal fistula
  evidence:
  - reference: ORPHA:1199
    reference_title: "Esophageal atresia"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002575 | Tracheoesophageal fistula | Very frequent (99-80%)"
    explanation: Orphanet lists tracheoesophageal fistula as very frequent in esophageal atresia.
  - reference: PMID:27993359
    reference_title: Perioperative management and outcomes of esophageal atresia and tracheoesophageal fistula.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The most common anatomy was proximal EA with distal TEF (n=335; 85%)"
    explanation: This multi-institutional cohort supports distal TEF as the most common anatomy.
- category: Cardiovascular
  name: Clinically significant congenital heart disease
  frequency: FREQUENT
  description: >-
    Congenital cardiovascular anomalies are common associated malformations in
    EA/TEF cohorts and carry prognostic significance.
  phenotype_term:
    preferred_term: Clinically significant congenital heart disease
    term:
      id: HP:0030680
      label: Abnormal cardiovascular system morphology
  evidence:
  - reference: PMID:27993359
    reference_title: Perioperative management and outcomes of esophageal atresia and tracheoesophageal fistula.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Clinically significant congenital heart disease (CHD) was present in 137 (35%)."
    explanation: This surgical cohort directly quantifies clinically significant congenital heart disease in 35% of EA/TEF cases.
  - reference: PMID:27993359
    reference_title: Perioperative management and outcomes of esophageal atresia and tracheoesophageal fistula.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Mortality was 7.5% and significantly associated with CHD"
    explanation: This supports the prognostic significance of congenital heart disease in the cohort.
  - reference: ORPHA:1199
    reference_title: "Esophageal atresia"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0030680 | Abnormal cardiovascular system morphology | Occasional (29-5%)"
    explanation: Orphanet independently lists abnormal cardiovascular morphology among associated EA phenotypes.
- category: Gastrointestinal
  name: Dysphagia
  frequency: FREQUENT
  description: Swallowing difficulty is a frequent clinical problem before and after repair.
  phenotype_term:
    preferred_term: Dysphagia
    term:
      id: HP:0002015
      label: Dysphagia
  evidence:
  - reference: ORPHA:1199
    reference_title: "Esophageal atresia"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002015 | Dysphagia | Frequent (79-30%)"
    explanation: Orphanet lists dysphagia as frequent in esophageal atresia.
  - reference: PMID:27579697
    reference_title: ESPGHAN-NASPGHAN Guidelines for the Evaluation and Treatment of Gastrointestinal and Nutritional Complications in Children With Esophageal Atresia-Tracheoesophageal Fistula.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "investigation and management of dysphagia"
    explanation: The guideline includes dysphagia among common EA complications requiring evaluation and management.
- category: Gastrointestinal
  name: Excessive salivation
  frequency: FREQUENT
  description: Pooling of secretions from proximal esophageal obstruction commonly produces excessive salivation.
  phenotype_term:
    preferred_term: Excessive salivation
    term:
      id: HP:0003781
      label: Excessive salivation
  evidence:
  - reference: ORPHA:1199
    reference_title: "Esophageal atresia"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0003781 | Excessive salivation | Frequent (79-30%)"
    explanation: Orphanet lists excessive salivation as frequent in esophageal atresia.
- category: Gastrointestinal
  name: Feeding difficulties in infancy
  frequency: FREQUENT
  description: Infants have feeding difficulty because the esophagus does not conduct feeds normally to the stomach.
  phenotype_term:
    preferred_term: Feeding difficulties in infancy
    term:
      id: HP:0008872
      label: Feeding difficulties in infancy
  evidence:
  - reference: ORPHA:1199
    reference_title: "Esophageal atresia"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0008872 | Feeding difficulties in infancy | Frequent (79-30%)"
    explanation: Orphanet lists infant feeding difficulty as frequent.
  - reference: PMID:27579697
    reference_title: ESPGHAN-NASPGHAN Guidelines for the Evaluation and Treatment of Gastrointestinal and Nutritional Complications in Children With Esophageal Atresia-Tracheoesophageal Fistula.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "feeding difficulties, anastomotic strictures, congenital esophageal stenosis in EA patients"
    explanation: The guideline directly identifies feeding difficulties among EA complications.
- category: Growth
  name: Failure to thrive in infancy
  frequency: FREQUENT
  description: Persistent feeding and aerodigestive morbidity can impair infant growth.
  phenotype_term:
    preferred_term: Failure to thrive in infancy
    term:
      id: HP:0001531
      label: Failure to thrive in infancy
  evidence:
  - reference: ORPHA:1199
    reference_title: "Esophageal atresia"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0001531 | Failure to thrive in infancy | Frequent (79-30%)"
    explanation: Orphanet lists failure to thrive in infancy as frequent.
- category: Respiratory
  name: Respiratory distress
  frequency: OCCASIONAL
  description: Severe neonatal esophageal atresia presentations can include respiratory distress.
  phenotype_term:
    preferred_term: Respiratory distress
    term:
      id: HP:0002098
      label: Respiratory distress
  evidence:
  - reference: ORPHA:1199
    reference_title: "Esophageal atresia"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002098 | Respiratory distress | Occasional (29-5%)"
    explanation: Orphanet lists respiratory distress as occasional.
  - reference: ORPHA:1199
    reference_title: "Esophageal atresia"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "in the most severe cases, respiratory distress"
    explanation: The Orphanet definition directly describes respiratory distress in severe cases.
- category: Respiratory
  name: Recurrent respiratory infections
  frequency: FREQUENT
  description: Respiratory morbidity after EA/TEF can include recurrent respiratory infections.
  phenotype_term:
    preferred_term: Recurrent respiratory infections
    term:
      id: HP:0002205
      label: Recurrent respiratory infections
  evidence:
  - reference: ORPHA:1199
    reference_title: "Esophageal atresia"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002205 | Recurrent respiratory infections | Frequent (79-30%)"
    explanation: Orphanet lists recurrent respiratory infections as frequent.
  - reference: PMID:31000707
    reference_title: Oesophageal atresia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "long-term gastrointestinal and respiratory complications and comorbidities in patients born with EA are common"
    explanation: The disease primer supports respiratory complications as common after EA.
- category: Respiratory
  name: Restrictive ventilatory defect
  frequency: FREQUENT
  description: Pulmonary function abnormalities can occur in the long-term respiratory phenotype of esophageal atresia.
  phenotype_term:
    preferred_term: Restrictive ventilatory defect
    term:
      id: HP:0002091
      label: Restrictive ventilatory defect
  evidence:
  - reference: ORPHA:1199
    reference_title: "Esophageal atresia"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002091 | Restrictive ventilatory defect | Frequent (79-30%)"
    explanation: Orphanet lists restrictive ventilatory defect as frequent.
- category: Gastrointestinal
  name: Gastrointestinal dysmotility
  frequency: FREQUENT
  description: Esophageal motility disorders are a common post-repair contributor to GI morbidity.
  phenotype_term:
    preferred_term: Gastrointestinal dysmotility
    term:
      id: HP:0002579
      label: Gastrointestinal dysmotility
  evidence:
  - reference: ORPHA:1199
    reference_title: "Esophageal atresia"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002579 | Gastrointestinal dysmotility | Frequent (79-30%)"
    explanation: Orphanet lists gastrointestinal dysmotility as frequent.
  - reference: PMID:31000707
    reference_title: Oesophageal atresia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Oesophageal motility disorders are probably ubiquitous in patients after undergoing EA repair"
    explanation: The disease primer supports post-repair esophageal dysmotility as very common.
- category: Gastrointestinal
  name: Gastroesophageal reflux
  frequency: OCCASIONAL
  description: GERD is a recognized post-repair gastrointestinal complication.
  phenotype_term:
    preferred_term: Gastroesophageal reflux
    term:
      id: HP:0002020
      label: Gastroesophageal reflux
  evidence:
  - reference: ORPHA:1199
    reference_title: "Esophageal atresia"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002020 | Gastroesophageal reflux | Occasional (29-5%)"
    explanation: Orphanet lists gastroesophageal reflux as occasional.
  - reference: PMID:27579697
    reference_title: ESPGHAN-NASPGHAN Guidelines for the Evaluation and Treatment of Gastrointestinal and Nutritional Complications in Children With Esophageal Atresia-Tracheoesophageal Fistula.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "diagnosis, and treatment of gastroesophageal reflux"
    explanation: The guideline specifically addresses GERD diagnosis and treatment in children with EA/TEF.
- category: Prenatal
  name: Absence of stomach bubble on fetal sonography
  frequency: FREQUENT
  diagnostic: true
  description: Prenatal sonography may show an absent fetal stomach bubble.
  phenotype_term:
    preferred_term: Absence of stomach bubble on fetal sonography
    term:
      id: HP:0010963
      label: Absence of stomach bubble on fetal sonography
  evidence:
  - reference: ORPHA:1199
    reference_title: "Esophageal atresia"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0010963 | Absence of stomach bubble on fetal sonography | Frequent (79-30%)"
    explanation: Orphanet lists absent stomach bubble on fetal sonography as frequent.
  - reference: PMID:22247246
    reference_title: "Oesophageal atresia: prevalence, prenatal diagnosis and associated anomalies in 23 European regions."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Prenatal detection rates varied by registry from >50% of cases to <10% of cases."
    explanation: Registry data support prenatal detection as part of the clinical diagnostic course.
- category: Respiratory
  name: Aspiration
  frequency: OCCASIONAL
  description: Fistulous airway communication and impaired swallowing can lead to aspiration.
  phenotype_term:
    preferred_term: Aspiration
    term:
      id: HP:0002835
      label: Aspiration
  evidence:
  - reference: ORPHA:1199
    reference_title: "Esophageal atresia"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0002835 | Aspiration | Occasional (29-5%)"
    explanation: Orphanet lists aspiration as an occasional phenotype.
- category: Gastrointestinal
  name: Esophagitis
  frequency: FREQUENT
  description: Reflux and dysmotility after EA repair can be associated with esophagitis.
  phenotype_term:
    preferred_term: Esophagitis
    term:
      id: HP:0100633
      label: Esophagitis
  evidence:
  - reference: ORPHA:1199
    reference_title: "Esophageal atresia"
    supports: SUPPORT
    evidence_source: OTHER
    snippet: "HP:0100633 | Esophagitis | Frequent (79-30%)"
    explanation: Orphanet lists esophagitis as frequent.
genetic:
- name: Syndromic and chromosomal associations
  association: Syndromic and chromosomal association
  presence: Positive
  features: >-
    Esophageal atresia frequently occurs with associated anomalies and can be
    part of VACTERL association, CHARGE syndrome, trisomies 18 or 21, and other
    defined genetic or chromosomal syndromes.
  evidence:
  - reference: PMID:31000707
    reference_title: Oesophageal atresia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Associated birth defects or anomalies, such as VACTERL association, trisomy 18 or 21 and CHARGE syndrome, occur in the majority of patients born with EA."
    explanation: The disease primer supports common syndromic and chromosomal associations in EA.
  - reference: PMID:20425471
    reference_title: "Etiology of esophageal atresia and tracheoesophageal fistula: \"mind the gap\"."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "In 6% to 10% of patients a defined genetic syndrome can be diagnosed"
    explanation: This review quantifies defined genetic syndrome diagnoses among EA/TEF patients.
  - reference: PMID:20425471
    reference_title: "Etiology of esophageal atresia and tracheoesophageal fistula: \"mind the gap\"."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Many well-known chromosomal aberrations are observed in EA/TEF patients, such as Down syndrome (trisomy 21), Edwards syndrome (trisomy 18), and Patau syndrome (trisomy 13)"
    explanation: This review documents chromosomal trisomies and other chromosomal aberrations in EA/TEF patients.
- name: VACTERL association
  association: Syndromic association
  presence: Positive
  features: >-
    VACTERL association is a common associated anomaly pattern in EA/TEF and
    includes vertebral, anal, cardiovascular, tracheoesophageal, renal, and limb
    anomalies.
  evidence:
  - reference: PMID:20425471
    reference_title: "Etiology of esophageal atresia and tracheoesophageal fistula: \"mind the gap\"."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "EA/TEF is a component of the VACTERL association, which includes vertebral, anal, cardiovascular, tracheoesophageal, renal, and limb anomalies, and is seen in 10% to 30% of EA/TEF patients [1, 19]."
    explanation: This review directly supports VACTERL association as a frequent associated context in EA/TEF.
- name: CHD7-associated CHARGE syndrome
  association: Syndromic association
  relationship_type: SUSCEPTIBILITY
  presence: Positive
  gene_term:
    preferred_term: CHD7
    term:
      id: hgnc:20626
      label: CHD7
  features: CHD7-related CHARGE syndrome can include EA/TEF as a syndromic feature.
  evidence:
  - reference: PMID:20425471
    reference_title: "Etiology of esophageal atresia and tracheoesophageal fistula: \"mind the gap\"."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "About 10% of patients with CHARGE syndrome display EA/TEF."
    explanation: This review supports EA/TEF as a feature in a subset of CHARGE syndrome patients.
  - reference: PMID:20425471
    reference_title: "Etiology of esophageal atresia and tracheoesophageal fistula: \"mind the gap\"."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "caused by mutations in the chromodomain helicase DNA-binding (CHD7) gene"
    explanation: This supports CHD7 as the gene underlying the relevant syndromic association.
- name: MYCN-associated Feingold syndrome
  association: Syndromic association
  relationship_type: SUSCEPTIBILITY
  presence: Positive
  gene_term:
    preferred_term: MYCN
    term:
      id: hgnc:7559
      label: MYCN
  features: MYCN-related Feingold syndrome is a familial syndromic gastrointestinal atresia context that commonly includes EA/TEF.
  evidence:
  - reference: PMID:20425471
    reference_title: "Etiology of esophageal atresia and tracheoesophageal fistula: \"mind the gap\"."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Feingold syndrome is caused by germline mutations in, or deletions of, the MYCN gene on chromosome 2p24.1."
    explanation: This review identifies MYCN as the causal gene for the Feingold syndrome association.
  - reference: PMID:20425471
    reference_title: "Etiology of esophageal atresia and tracheoesophageal fistula: \"mind the gap\"."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "About 30% to 40% of patients diagnosed with Feingold syndrome have EA/TEF [25]."
    explanation: This review directly supports EA/TEF enrichment in Feingold syndrome.
- name: SOX2-associated anophthalmia-esophageal-genital syndrome
  association: Syndromic association
  relationship_type: SUSCEPTIBILITY
  presence: Positive
  gene_term:
    preferred_term: SOX2
    term:
      id: hgnc:11195
      label: SOX2
  features: SOX2 deletions or mutations can produce a syndromic phenotype including esophageal atresia.
  evidence:
  - reference: PMID:20425471
    reference_title: "Etiology of esophageal atresia and tracheoesophageal fistula: \"mind the gap\"."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Deletions and mutations of the SOX2 gene are causative for the phenotype of clinical anophthalmia/optic nerve hypoplasia, esophageal atresia, and/or genital anomalies in the AEG syndrome [28]."
    explanation: This review directly links SOX2 alterations to a syndromic phenotype including esophageal atresia.
- name: FOXF1 and sonic hedgehog pathway developmental susceptibility
  association: Developmental susceptibility
  relationship_type: SUSCEPTIBILITY
  presence: Positive
  gene_term:
    preferred_term: FOXF1
    term:
      id: hgnc:3809
      label: FOXF1
  features: >-
    FOXF1 and sonic hedgehog pathway effectors are implicated by human
    chromosomal-deletion observations and model-organism studies of foregut
    development.
  evidence:
  - reference: PMID:20425471
    reference_title: "Etiology of esophageal atresia and tracheoesophageal fistula: \"mind the gap\"."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "mutations in the FOXF1 gene, in patients with alveolar capillary dysplasia combined with VACTERL-associated anomalies, including EA/TEF [24••]."
    explanation: This review links FOXF1-region alterations to human VACTERL-associated anomalies including EA/TEF.
  - reference: PMID:20425471
    reference_title: "Etiology of esophageal atresia and tracheoesophageal fistula: \"mind the gap\"."
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Genes of developmental pathways are involved, including vitamin A effectors (Rarα, Rarβ), effectors of the sonic hedgehog (SHH) pathway (Shh, Gli2, Gli3, Foxf1)"
    explanation: This supports FOXF1 and SHH-pathway effectors as model-organism developmental susceptibility genes for tracheoesophageal anomalies.
diagnosis:
- name: Nasogastric tube passage with chest radiograph
  description: >-
    In the newborn period, inability to pass a nasogastric tube and radiographic
    localization of the arrested tube support diagnosis and can help estimate
    esophageal gap length before repair.
  diagnosis_term:
    preferred_term: radiograph imaging procedure
    term:
      id: NCIT:C38101
      label: X-Ray Imaging
  results: Arrested nasogastric tube in the upper esophageal pouch; esophageal gap length estimate.
  evidence:
  - reference: PMID:31571760
    reference_title: Prediction of Gap Length by Plain Radiograph of Chest with Nasogastric Tube in the Upper Esophagus in Patients with Esophageal Atresia and Distal Tracheoesophageal Fistula.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Plain radiograph including chest and abdomen with nasogastric tube no 8 Fr in the upper esophagus were taken for all patients to confirm the diagnosis"
    explanation: This prospective cohort directly supports radiography with a nasogastric tube for diagnosis.
  - reference: PMID:27190912
    reference_title: Appearances are Deceptive - Passing a Nasogastric Tube does Not Always Rule Out Oesophageal Atresia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "confirmed by contrast study showing blind upper oesophageal pouch."
    explanation: This case report supports imaging confirmation of a blind upper esophageal pouch.
- name: Post-repair motility and reflux assessment
  description: >-
    High-resolution impedance manometry and pH-multichannel intraluminal
    impedance testing can characterize post-repair dysmotility and reflux burden.
  diagnosis_term:
    preferred_term: clinical assessment
    term:
      id: NCIT:C124351
      label: Clinical Evaluation
  results: Esophageal motility pattern, reflux burden, and symptom correlation.
  evidence:
  - reference: PMID:31000707
    reference_title: Oesophageal atresia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "including high-resolution impedance manometry, pH-multichannel intraluminal impedance testing"
    explanation: The disease primer identifies manometry and pH-impedance testing as clinical tools for post-repair morbidity.
treatments:
- name: Primary surgical repair with tracheoesophageal fistula ligation
  description: >-
    Standard neonatal management restores esophageal continuity and ligates or
    divides a tracheoesophageal fistula when present.
  treatment_term:
    preferred_term: surgical repair
    term:
      id: NCIT:C15329
      label: Surgical Procedure
  target_phenotypes:
  - preferred_term: Esophageal atresia
    term:
      id: HP:0002032
      label: Esophageal atresia
  - preferred_term: Tracheoesophageal fistula
    term:
      id: HP:0002575
      label: Tracheoesophageal fistula
  evidence:
  - reference: PMID:31000707
    reference_title: Oesophageal atresia.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "EA is treated surgically to restore the oesophageal interruption and, if present, ligate and divide the TEF."
    explanation: The disease primer directly states the surgical repair goals.
  - reference: PMID:27993359
    reference_title: Perioperative management and outcomes of esophageal atresia and tracheoesophageal fistula.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "surgical repair of their defect defined as esophageal reconstruction with or without ligation of TEF"
    explanation: The surgical cohort defines repair as esophageal reconstruction with or without TEF ligation.
- name: Gastroesophageal reflux treatment
  description: >-
    Long-term care includes treatment of gastroesophageal reflux after EA/TEF
    repair.
  treatment_term:
    preferred_term: Pharmacotherapy
    term:
      id: NCIT:C15986
      label: Pharmacotherapy
  target_phenotypes:
  - preferred_term: Gastroesophageal reflux
    term:
      id: HP:0002020
      label: Gastroesophageal reflux
  - preferred_term: Dysphagia
    term:
      id: HP:0002015
      label: Dysphagia
  evidence:
  - reference: PMID:27579697
    reference_title: ESPGHAN-NASPGHAN Guidelines for the Evaluation and Treatment of Gastrointestinal and Nutritional Complications in Children With Esophageal Atresia-Tracheoesophageal Fistula.
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Questions on the diagnosis, and treatment of gastroesophageal reflux"
    explanation: The guideline explicitly covers treatment of GERD in children with EA/TEF.
- name: Balloon dilatation for post-repair anastomotic strictures
  description: >-
    Anastomotic strictures after esophageal atresia repair are often managed
    with fluoroscopic or endoscopic balloon dilatation.
  treatment_term:
    preferred_term: endoscopic procedure
    term:
      id: NCIT:C16546
      label: Endoscopic Procedure
  target_phenotypes:
  - preferred_term: Dysphagia
    term:
      id: HP:0002015
      label: Dysphagia
  evidence:
  - reference: PMID:23877544
    reference_title: "Balloon dilatation of anastomotic strictures secondary to surgical repair of oesophageal atresia: a systematic review."
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "These strictures are often treated by balloon dilatation (BD) and currently balloon dilatation (fluoroscopic or endoscopic) is the preferred primary treatment method."
    explanation: This systematic review directly supports balloon dilatation for anastomotic strictures after EA repair.
notes: >-
  Orphanet lists additional occasional or rare associated congenital anomalies,
  including VACTERL-associated features. This entry emphasizes the core
  esophageal atresia phenotype and direct aerodigestive sequelae rather than
  uncritically importing all syndromic associated anomalies.
datasets:
- accession: geo:GSE305960
  title: Investigating the mechanisms by which SMAD6 mutations cause tracheoesophageal birth defects
  description: Esophageal atresia (EA) with or without tracheoesophageal fistula (TEF) are tracheoesophageal (TE) birth defects which affect 1 in 3000 live births in the United States. EA occurs when the esophagus fails to form a continuous tube from the oral cavity to the stomach and TEF occurs when there is an abnormal connection between the trachea and esophagus. The etiology of EA/TEF arises when the common foregut tube fails to properly separate into the esophagus and respiratory tract during early embryogenesis. This process is essential for proper organ function and involves complex molecular and morphological processes.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_count: 54
  notes: Identified by GEO DataSets index search for Esophageal Atresia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE203126
  title: Chromosomal abnormalities and pregnancy outcomes for fetuses with gastrointestinal tract obstructions
  description: Fetal gastrointestinal tract obstructions (GITO) is the most frequently encountered gastrointestinal defects in prenatal. This study aimed to investigate the genetic disorders and pregnancy outcomes of fetal GITO. We reviewed data from 70 pregnancies who were referred for invasive prenatal testing due to fetal GITO. According to the levels of obstruction, they were classified into esophageal atresia/stenosis, duodenal atresia/stenosis, jejunal or ileal atresia/stenosis, and anal atresia. Traditional karyotyping was performed on all 70 pregnancies, and chromosomal microarray analysis (CMA) was performed on 32 of them in parallel.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  sample_count: 32
  publication: PMID:35783302
  notes: Identified by GEO DataSets index search for Esophageal Atresia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: geo:GSE148247
  title: Tracheoesophageal fistula characterisation
  description: Esophageal atresia and tracheoesophageal fistula (EA/TEF) are relatively frequently occurring foregut malformations with a largely unknown etiology. EA/TEF is thought to have a strong genetic component and several genes have been proven to be involved in syndromic EA/TEF. However, it is not clear which biological processes or gene networks are disturbed. To gain more insight in the origin of the TEF, we aimed to examine and describe TEF composition using a combination of whole-genome transcription profiling and (immuno-) histochemical stainings. We hypothesized that such characterization of human TEFs provides insight in the molecular and mechanistic etiology of EA/TEF.
  organism:
    preferred_term: human
    term:
      id: NCBITaxon:9606
      label: Homo sapiens
  data_type: BULK_RNA_SEQ
  sample_count: 31
  publication: PMID:33201890
  notes: Identified by GEO DataSets index search for Esophageal Atresia (scripts/discover_datasets.py); accession and metadata verified against NCBI E-utilities on 2026-08-01. Title, sample count, and organism are GEO's own values.
- accession: dbgap:phs002161
  title: 'Kids First: Genomic Analysis of Esophageal Atresia and Tracheoesophageal Fistulas and Associated Congenital Anomalies'
  description:  The Gabriella Miller Kids First Pediatric Research Program (Kids First) is a trans-NIH effort initiated in response to the 2014 Gabriella Miller Kids First Research Act and supported by the NIH Common Fund. This program focuses on gene discovery in pediatric cancers and structural birth defects and the development of the Gabriella Miller Kids First Pediatric Data Resource (Kids First Data Resource).        All of the WGS and phenotypic data from this study are accessible through dbGaP and  kidsfirstdrc.org , where ot
  notes: Located via OmicsDI, which aggregates across omics repositories; this record comes from dbgap. Only repositories with no other discovery route in this project and with a working accession resolver are curated from OmicsDI -- GEO, ArrayExpress, PRIDE, MetaboLights and EGA hits are excluded as duplicates of dedicated passes. Matched because the disease is named in the dataset's own title ("Esophageal Atresia"). Retrieved 2026-08-02.
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References & Deep Research

Deep Research

1
Esophageal Atresia Evidence-Backed Research Fallback ▸

Esophageal Atresia Evidence-Backed Research Fallback

Provider Attempts

The Falcon deep-research command produced no usable output during the bounded wait and was terminated with signal 15. A secondary OpenAI deep-research attempt also remained silent during the bounded wait and was terminated with signal 15. No provider artifact was used for curation.

Evidence Synthesis

ORPHA:1199 defines esophageal atresia as interruption of esophageal continuity with or without persistent tracheal communication. The structured Orphanet cache also provides neonatal onset, European and United States prevalence bands, synonyms, exact MeSH and OMIM cross-references, and phenotype-frequency rows for tracheoesophageal fistula, dysphagia, excessive salivation, feeding difficulty, failure to thrive, recurrent respiratory infections, restrictive ventilatory defect, gastrointestinal dysmotility, gastroesophageal reflux, respiratory distress, aspiration, esophagitis, abnormal cardiovascular system morphology, and absent fetal stomach bubble.

PMID:22247246 provides independent population-based EUROCAT support for prevalence, prenatal detection, associated anomalies, live-born frequency, and early survival in European regions.

PMID:31000707 is the central disease-primer source. It supports incomplete foregut compartmentalization as the developmental cause, common tracheoesophageal fistula association, surgical restoration of esophageal continuity with TEF ligation/division, long-term gastrointestinal and respiratory morbidity, post-repair esophageal dysmotility, and diagnostic tools including high-resolution impedance manometry and pH-multichannel intraluminal impedance testing.

PMID:32515280 and PMID:20425471 provide developmental mechanism context. They support the shared anterior foregut origin of trachea and esophagus, disrupted foregut compartmentalization in EA/TEF, and model-organism evidence implicating multiple signaling pathways and transcription factors, including sonic hedgehog/smoothened pathway effectors, in foregut embryogenesis.

PMID:20425471 also supports the Gross anatomical subtype framework, defined by the location of atresia and the tracheoesophageal connection, and provides the core syndromic/genetic context for VACTERL association, CHARGE/CHD7, Feingold/MYCN, SOX2-associated AEG syndrome, chromosomal trisomies, FOXF1, and SHH-pathway developmental susceptibility. PMID:27993359 quantifies the dominant anatomical subtypes in a contemporary surgical cohort: proximal EA with distal TEF at 85% and pure EA at 7%.

PMID:27190912 and PMID:31571760 support newborn diagnosis by failed or misleading nasogastric-tube passage and chest/abdominal radiography with the tube arrested in the upper esophageal pouch. PMID:31571760 also supports using the radiograph to estimate esophageal gap length before repair.

PMID:27993359 supports contemporary surgical cohort context: most infants have proximal EA with distal TEF, surgical repair is esophageal reconstruction with or without TEF ligation, clinically significant congenital heart disease is present in 35%, postoperative morbidity is common, and perioperative practice varies substantially across centers.

PMID:27579697 provides guideline support for long-term care of reflux, dysphagia, feeding difficulty, anastomotic strictures, congenital esophageal stenosis, and other gastrointestinal complications after EA/TEF repair. PMID:23877544 provides systematic-review support for fluoroscopic or endoscopic balloon dilatation as primary treatment for anastomotic strictures after esophageal atresia repair.

Scope Confirmation

The YAML intentionally emphasizes the core congenital esophageal atresia/TEF phenotype and direct aerodigestive sequelae. It does not import every Orphanet occasional or rare associated anomaly because many reflect syndromic or VACTERL contexts rather than the core disorder mechanism.