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Laryngotracheoesophageal Cleft

Complex MONDO:0016060 tracheal disorder esophageal disorder

Congenital foregut partitioning defect characterized by an abnormal posterior communication between the larynx/trachea and the esophagus.

0
Mappings
0
Definitions
0
Inheritance
5
Pathophysiology
0
Histopathology
14
Phenotypes
4
Genes
6
Treatments
5
Subtypes
4
Differentials
0
Datasets
0
Trials
◆

Subtypes

5
Type 0 (interarytenoid cleft) Not Yet Curated MONDO:0017220
Interarytenoid notch above the vocal folds without extension into the cricoid cartilage.
Type I Not Yet Curated MONDO:0019761
Supraglottic cleft extending to, but not through, the cricoid cartilage.
Type II Not Yet Curated MONDO:0019762
Cleft extends through the cricoid cartilage into the cervical trachea.
Type III Not Yet Curated MONDO:0019763
Cleft extends into the thoracic trachea.
Type IV Not Yet Curated MONDO:0019764
Cleft extends to the carina and may involve a mainstem bronchus.
⚙

Pathophysiology

5
Failed foregut partitioning
Abnormal separation of the anterior foregut permits persistent communication between airway and esophagus.
digestive tract development link ↕ DYSREGULATED respiratory system development link ↕ DYSREGULATED
foregut link
Show evidence (2 references)
DOI:10.1186/s40792-023-01650-7 SUPPORT Human Clinical
"LTEC occurs because of foregut maldevelopment"
Case report links LTEC to foregut maldevelopment, supporting failed partitioning.
PMID:38380453 SUPPORT Human Clinical
"failure of separation of the trachea and the oesophagus during fetal development"
Case report reiterates fetal failure of trachea-esophagus separation in LTEC.
Disrupted BMP4 signaling during larynx development
Disruption of BMP4 signaling perturbs laryngeal development and is associated with laryngeal cleft in a mouse model.
BMP signaling pathway link ↕ DYSREGULATED larynx development link ↕ DYSREGULATED
Show evidence (1 reference)
PMID:37230380 SUPPORT Model Organism
"Disruption of BMP4 signaling is associated with laryngeal birth defects in a mouse model."
Mouse model demonstrates association of disrupted BMP4 signaling with laryngeal cleft.
Posterior communication between larynx/trachea and esophagus
Abnormal posterior cleft connects the larynx/trachea with the esophagus.
larynx link trachea link esophagus link
Show evidence (1 reference)
DOI:10.1186/s40792-023-01650-7 SUPPORT Human Clinical
"Laryngotracheoesophageal cleft (LTEC) is a rare disease in which the larynx and trachea communicate posteriorly to the esophagus."
Case report defines LTEC as a posterior larynx/trachea communication with the esophagus.
Foregut maldevelopment during respiratory and digestive tract development
Disrupted foregut development underlies formation of the cleft.
digestive tract development link ↕ DYSREGULATED respiratory system development link ↕ DYSREGULATED
foregut link
Show evidence (1 reference)
DOI:10.1186/s40792-023-01650-7 SUPPORT Human Clinical
"LTEC occurs because of foregut maldevelopment"
Case report links LTEC to foregut maldevelopment.
Enriched esophageal malformation gene expression in lateral plate mesoderm
Esophageal malformation genes show highest expression in lateral plate mesoderm during early development, implicating this tissue in maldevelopment.
lateral plate mesoderm link
Show evidence (1 reference)
DOI:10.1038/s41598-024-53098-w SUPPORT Computational
"the genes associated with esophageal malformations show their highest cell-type specific expression in lateral plate mesoderm cells and at the developmental stage of E8.75–E9.0 days."
Single-cell atlas analysis highlights lateral plate mesoderm enrichment of esophageal malformation genes.
●

Phenotypes

14
Digestive(2) Immune(2) Nervous System(1) Respiratory(8) Voice(1)
Digestive 2
Vomiting OCCASIONAL Vomiting (HP:0002013)
Show evidence (1 reference)
DOI:10.1186/s40792-023-01650-7 SUPPORT Human Clinical
"The patient experienced frequent vomiting and aspiration pneumonia"
Case report describes frequent vomiting in LTEC.
Dysphagia OCCASIONAL Dysphagia (HP:0002015)
Show evidence (1 reference)
PMID:37441989 SUPPORT Human Clinical
"children with dysphagia found to have a LC-1 or DIG on endoscopic exam"
Study cohort with LC-1/DIG demonstrates dysphagia assessed by VFSS.
Immune 2
Pneumonia OCCASIONAL Pneumonia (HP:0002090)
Show evidence (4 references)
DOI:10.1186/s40792-023-01650-7 SUPPORT Human Clinical
"The patient experienced frequent vomiting and aspiration pneumonia"
Case report documents aspiration pneumonia in LTEC.
PMID:32593610 SUPPORT Human Clinical
"He had chronic aspiration, recurrent pneumonia, and a hoarse voice for his entire life."
Adult case report documents recurrent pneumonia in a laryngeal cleft patient.
PMID:40227884 SUPPORT Human Clinical
"nearly half (44%) had a history of pneumonia"
Cohort study reports frequent pneumonia history in type 1 laryngeal cleft.
+ 1 more reference
Aspiration pneumonia OCCASIONAL Aspiration pneumonia (HP:0011951)
Show evidence (1 reference)
PMID:6873110 SUPPORT Human Clinical
"life-threatening disturbances in the form of asphyxia and aspiration pneumonia."
Review describes aspiration pneumonia as a key clinical disturbance.
Nervous System 1
Choking episodes OCCASIONAL Choking episodes (HP:0030842)
Show evidence (1 reference)
PMID:40330935 SUPPORT Human Clinical
"All patients experienced cough and choking with feeding."
Case series documents choking with feeding in type 1 laryngeal cleft.
Respiratory 8
Cough OCCASIONAL Cough (HP:0012735)
Show evidence (3 references)
PMID:32593610 SUPPORT Human Clinical
"a 56-year-old male referred for hoarseness and chronic cough that was discovered to have a type 2 laryngeal cleft."
Adult case report documents chronic cough in laryngeal cleft.
PMID:39543566 SUPPORT Human Clinical
"severe coughing"
Case report describes severe coughing in a child with a posterior laryngeal cleft.
PMID:40330935 SUPPORT Human Clinical
"All patients experienced cough and choking with feeding."
Case series reports cough as a common presenting symptom in type 1 laryngeal cleft.
Upper airway obstruction RARE Upper airway obstruction (HP:0002781)
Show evidence (1 reference)
PMID:37436152 SUPPORT Human Clinical
"the sole presenting feature may be airway obstruction."
Case report notes upper airway obstruction as the presenting feature in type III clefts without aspiration.
Stridor RARE Stridor (HP:0010307)
Show evidence (1 reference)
PMID:40330935 SUPPORT Human Clinical
"one had a stridor"
Case series reports stridor in a subset of type 1 laryngeal cleft patients.
Dyspnea OCCASIONAL Dyspnea (HP:0002094)
Show evidence (2 references)
PMID:30783751 SUPPORT Human Clinical
"showed severe dyspnea and dysphagia"
Case report documents severe dyspnea in type IV LTEC.
PMID:39543566 SUPPORT Human Clinical
"shortness of breath"
Case report describes shortness of breath in a child with posterior laryngeal cleft.
Wheezing OCCASIONAL Wheezing (HP:0030828)
Show evidence (1 reference)
PMID:39543566 SUPPORT Human Clinical
"severe wheezing"
Case report notes severe wheezing in a child with posterior laryngeal cleft.
Aspiration OCCASIONAL Aspiration (HP:0002835)
Show evidence (1 reference)
PMID:40227884 SUPPORT Human Clinical
"can result in chronic microaspiration and subsequent lung disease"
Cohort study highlights chronic microaspiration in type 1 laryngeal cleft.
Atelectasis FREQUENT Atelectasis (HP:0100750)
Show evidence (1 reference)
PMID:40227884 SUPPORT Human Clinical
"atelectasis (56%)"
Cohort study reports atelectasis as a common radiographic finding in type 1 laryngeal cleft.
Bronchial wall thickening FREQUENT Bronchial wall thickening (HP:0033542)
Show evidence (1 reference)
PMID:40227884 SUPPORT Human Clinical
"bronchial wall thickening (59%)"
Cohort study reports bronchial wall thickening as a prevalent radiographic finding.
Voice 1
Hoarse voice OCCASIONAL Hoarse voice (HP:0001609)
Show evidence (2 references)
PMID:32593610 SUPPORT Human Clinical
"referred for hoarseness and chronic cough"
Adult case report lists hoarseness as a presenting symptom.
PMID:39543566 SUPPORT Human Clinical
"He presented with hoarseness"
Pediatric case report notes hoarseness with posterior laryngeal cleft.
🧬

Genetic Associations

4
SOX2 (Associated)
Show evidence (1 reference)
DOI:10.1038/s41598-024-53098-w SUPPORT Computational
"FOXF1, FOXC1, and FOXD1, as well as the SRY-box transcription factor, SOX2, demonstrate the most significant preferential expression in both mouse and human embryos."
Single-cell analysis links SOX2 to esophageal malformation gene expression patterns.
FOXF1 (Associated)
Show evidence (1 reference)
DOI:10.1038/s41598-024-53098-w SUPPORT Computational
"FOXF1, FOXC1, and FOXD1, as well as the SRY-box transcription factor, SOX2, demonstrate the most significant preferential expression in both mouse and human embryos."
Single-cell analysis highlights FOXF1 among genes enriched in esophageal malformation contexts.
FOXC1 (Associated)
Show evidence (1 reference)
DOI:10.1038/s41598-024-53098-w SUPPORT Computational
"FOXF1, FOXC1, and FOXD1, as well as the SRY-box transcription factor, SOX2, demonstrate the most significant preferential expression in both mouse and human embryos."
Single-cell analysis highlights FOXC1 among genes enriched in esophageal malformation contexts.
RERE (Associated)
Show evidence (1 reference)
PMID:30245899 SUPPORT Human Clinical
"a 1p36 deletion including the RERE gene was detected."
Case report identifies a 1p36 deletion including RERE in a neonate with type IV LTEC.
💊

Treatments

6
Endoscopic laser repair (type 1) MAXO:0001578
Endoscopic laser repair used for type 1 laryngeal clefts.
Show evidence (1 reference)
PMID:40330935 SUPPORT Human Clinical
"endoscopic laser repair remains the gold standard treatment for type 1 LC."
Case series identifies endoscopic laser repair as the standard treatment for type 1 laryngeal cleft.
Endoscopic CO2 laser repair (type 3) MAXO:0001578
Staged endoscopic CO2 laser-assisted repair for type 3 clefts.
Show evidence (1 reference)
PMID:40579891 SUPPORT Human Clinical
"Nineteen patients with Type III laryngeal clefts who were treated with endoscopic carbon dioxide laser-assisted repair were included."
Case series reports staged endoscopic CO2 laser repair for type 3 clefts.
Injection laryngoplasty MAXO:0000004
Injection laryngoplasty used as a diagnostic or temporizing intervention in laryngeal cleft.
Show evidence (3 references)
PMID:39260330 SUPPORT Human Clinical
"LC can be treated surgically by performing suture repair or by Injection Laryngoplasty (IL)."
Survey study identifies injection laryngoplasty as a treatment option for laryngeal cleft.
PMID:40330935 SUPPORT Human Clinical
"we initially managed patients with type 1 LC with hyaluronic acid injections for a few months"
Case series documents injection laryngoplasty used in initial management.
PMID:35236684 SUPPORT Human Clinical
"injection laryngoplasty is performed safely on an 8-week-old child"
Case report supports injection laryngoplasty as a feasible intervention in infants.
Surgical repair of laryngeal cleft MAXO:0000004
Operative repair of laryngeal cleft improves aspiration symptoms.
Show evidence (6 references)
PMID:40629707 SUPPORT Human Clinical
"All showed marked improvement after surgical repair."
Familial case report shows symptom improvement after surgical repair.
PMID:6873110 SUPPORT Human Clinical
"an early operative correction of the defect is required."
Review emphasizes early operative correction for laryngotracheoesophageal cleft.
PMID:30783751 SUPPORT Human Clinical
"repair of the cleft was performed by an anterior approach via median sternotomy"
Type IV case report documents surgical repair of LTEC with an anterior approach under ECMO.
+ 3 more references
Anterior laryngofissure repair with posterior cartilage grafting MAXO:0000004
Anterior approach surgical repair with posterior cartilage grafting for type III/IV LTEC.
Show evidence (1 reference)
PMID:38761217 SUPPORT Human Clinical
"an anterior approach that involved interposition a posterior cartilage for Type III or Type IV laryngotracheoesophageal cleft (LTEC)."
Surgical series supports anterior laryngofissure repair with posterior cartilage grafting for type III/IV LTEC.
Combined open and endoscopic repair for long clefts MAXO:0000004
Combined open and endoscopic approaches may be required for long clefts with tracheal extension.
Show evidence (1 reference)
PMID:37816841 SUPPORT Human Clinical
"Primary and revision repair of long clefts with tracheal extension may require a combined approach."
Series reports use of combined open and endoscopic approaches for long clefts.
🔀

Differential Diagnoses

4

Conditions with similar clinical presentations that must be differentiated from Laryngotracheoesophageal Cleft:

Esophageal atresia Not Yet Curated MONDO:0001044
Overlapping Features Prenatal imaging features of LTEC can mimic esophageal atresia.
Show evidence (1 reference)
PMID:30232040 SUPPORT Human Clinical
"Laryngotracheoesophageal cleft, a rare differential diagnosis of esophageal atresia."
Case report highlights LTEC as a differential diagnosis for esophageal atresia.
Tracheo-esophageal fistula Not Yet Curated MONDO:0018694
Overlapping Features Fistulous communication can resemble LTEC and must be distinguished.
Show evidence (1 reference)
PMID:22151899 SUPPORT Human Clinical
"Differential diagnoses include tracheo-bronchial fistula, gastro-esophageal reflux disease and neurological swallowing disorders, as well as laryngomalacia and laryngeal palsy."
Review lists tracheo-bronchial fistula among LTEC differentials.
Gastroesophageal reflux disease MONDO:0007186
Overlapping Features GERD can present with aspiration and feeding symptoms that overlap with LTEC.
Show evidence (1 reference)
PMID:22151899 SUPPORT Human Clinical
"Differential diagnoses include tracheo-bronchial fistula, gastro-esophageal reflux disease and neurological swallowing disorders, as well as laryngomalacia and laryngeal palsy."
Review lists GERD among LTEC differential diagnoses.
Congenital laryngomalacia Not Yet Curated MONDO:0007878
Overlapping Features Laryngomalacia can cause stridor and aspiration symptoms resembling LTEC.
Show evidence (1 reference)
PMID:22151899 SUPPORT Human Clinical
"Differential diagnoses include tracheo-bronchial fistula, gastro-esophageal reflux disease and neurological swallowing disorders, as well as laryngomalacia and laryngeal palsy."
Review lists laryngomalacia among LTEC differential diagnoses.
{ }

Source YAML

click to show 
name: Laryngotracheoesophageal Cleft
creation_date: '2026-02-03T18:21:46Z'
updated_date: '2026-02-17T21:53:14Z'
category: Complex
synonyms:
- Laryngeal cleft
- Laryngotracheoesophageal cleft
- Laryngotracheal cleft
description: >-
  Congenital foregut partitioning defect characterized by an abnormal posterior
  communication between the larynx/trachea and the esophagus.
disease_term:
  preferred_term: laryngotracheoesophageal cleft
  term:
    id: MONDO:0016060
    label: laryngotracheoesophageal cleft
parents:
- tracheal disorder
- esophageal disorder
prevalence:
- population: Infants undergoing flexible endoscopy at a tertiary care center
  percentage: 0.28
  notes: Proportion of infants diagnosed with laryngeal cleft among those
    undergoing flexible endoscopy at a single institution.
  evidence:
  - reference: PMID:35596199
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "This equates to a prevalence of 0.28% in all the children who underwent
      flexible endoscopy at our institution."
    explanation: Study reports a 0.28% prevalence among children undergoing
      flexible endoscopy.
has_subtypes:
- name: Type 0 (interarytenoid cleft)
  description: Interarytenoid notch above the vocal folds without extension into
    the cricoid cartilage.
  subtype_term:
    preferred_term: laryngotracheoesophageal cleft type 0
    term:
      id: MONDO:0017220
      label: laryngotracheoesophageal cleft type 0
- name: Type I
  description: Supraglottic cleft extending to, but not through, the cricoid
    cartilage.
  subtype_term:
    preferred_term: laryngotracheoesophageal cleft type 1
    term:
      id: MONDO:0019761
      label: laryngotracheoesophageal cleft type 1
- name: Type II
  description: Cleft extends through the cricoid cartilage into the cervical
    trachea.
  subtype_term:
    preferred_term: laryngotracheoesophageal cleft type 2
    term:
      id: MONDO:0019762
      label: laryngotracheoesophageal cleft type 2
- name: Type III
  description: Cleft extends into the thoracic trachea.
  subtype_term:
    preferred_term: laryngotracheoesophageal cleft type 3
    term:
      id: MONDO:0019763
      label: laryngotracheoesophageal cleft type 3
- name: Type IV
  description: Cleft extends to the carina and may involve a mainstem bronchus.
  subtype_term:
    preferred_term: laryngotracheoesophageal cleft type 4
    term:
      id: MONDO:0019764
      label: laryngotracheoesophageal cleft type 4
pathophysiology:
- name: Failed foregut partitioning
  description: Abnormal separation of the anterior foregut permits persistent
    communication between airway and esophagus.
  locations:
  - preferred_term: foregut
    term:
      id: UBERON:0001041
      label: foregut
  biological_processes:
  - preferred_term: digestive tract development
    term:
      id: GO:0048565
      label: digestive tract development
    modifier: DYSREGULATED
  - preferred_term: respiratory system development
    term:
      id: GO:0060541
      label: respiratory system development
    modifier: DYSREGULATED
  evidence:
  - reference: DOI:10.1186/s40792-023-01650-7
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "LTEC occurs because of foregut maldevelopment"
    explanation: Case report links LTEC to foregut maldevelopment, supporting
      failed partitioning.
  - reference: PMID:38380453
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "failure of separation of the trachea and the oesophagus during fetal
      development"
    explanation: Case report reiterates fetal failure of trachea-esophagus
      separation in LTEC.
- name: Disrupted BMP4 signaling during larynx development
  description: Disruption of BMP4 signaling perturbs laryngeal development and
    is associated with laryngeal cleft in a mouse model.
  biological_processes:
  - preferred_term: BMP signaling pathway
    term:
      id: GO:0030509
      label: BMP signaling pathway
    modifier: DYSREGULATED
  - preferred_term: larynx development
    term:
      id: GO:0120224
      label: larynx development
    modifier: DYSREGULATED
  evidence:
  - reference: PMID:37230380
    supports: SUPPORT
    evidence_source: MODEL_ORGANISM
    snippet: "Disruption of BMP4 signaling is associated with laryngeal birth defects
      in a mouse model."
    explanation: Mouse model demonstrates association of disrupted BMP4
      signaling with laryngeal cleft.
- name: Posterior communication between larynx/trachea and esophagus
  description: Abnormal posterior cleft connects the larynx/trachea with the
    esophagus.
  locations:
  - preferred_term: larynx
    term:
      id: UBERON:0001737
      label: larynx
  - preferred_term: trachea
    term:
      id: UBERON:0003126
      label: trachea
  - preferred_term: esophagus
    term:
      id: UBERON:0001043
      label: esophagus
  evidence:
  - reference: DOI:10.1186/s40792-023-01650-7
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Laryngotracheoesophageal cleft (LTEC) is a rare disease in which the
      larynx and trachea communicate posteriorly to the esophagus."
    explanation: Case report defines LTEC as a posterior larynx/trachea
      communication with the esophagus.
- name: Foregut maldevelopment during respiratory and digestive tract
    development
  description: Disrupted foregut development underlies formation of the cleft.
  locations:
  - preferred_term: foregut
    term:
      id: UBERON:0001041
      label: foregut
  biological_processes:
  - preferred_term: digestive tract development
    term:
      id: GO:0048565
      label: digestive tract development
    modifier: DYSREGULATED
  - preferred_term: respiratory system development
    term:
      id: GO:0060541
      label: respiratory system development
    modifier: DYSREGULATED
  evidence:
  - reference: DOI:10.1186/s40792-023-01650-7
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "LTEC occurs because of foregut maldevelopment"
    explanation: Case report links LTEC to foregut maldevelopment.
- name: Enriched esophageal malformation gene expression in lateral plate
    mesoderm
  description: Esophageal malformation genes show highest expression in lateral
    plate mesoderm during early development, implicating this tissue in
    maldevelopment.
  locations:
  - preferred_term: lateral plate mesoderm
    term:
      id: UBERON:0003081
      label: lateral plate mesoderm
  evidence:
  - reference: DOI:10.1038/s41598-024-53098-w
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: "the genes associated with esophageal malformations show their highest
      cell-type specific expression in lateral plate mesoderm cells and at the developmental
      stage of E8.75–E9.0 days."
    explanation: Single-cell atlas analysis highlights lateral plate mesoderm
      enrichment of esophageal malformation genes.
phenotypes:
- name: Vomiting
  category: Gastrointestinal
  frequency: OCCASIONAL
  phenotype_term:
    preferred_term: Vomiting
    term:
      id: HP:0002013
      label: Vomiting
  evidence:
  - reference: DOI:10.1186/s40792-023-01650-7
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The patient experienced frequent vomiting and aspiration pneumonia"
    explanation: Case report describes frequent vomiting in LTEC.
- name: Pneumonia
  category: Respiratory
  frequency: OCCASIONAL
  phenotype_term:
    preferred_term: Pneumonia
    term:
      id: HP:0002090
      label: Pneumonia
  evidence:
  - reference: DOI:10.1186/s40792-023-01650-7
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The patient experienced frequent vomiting and aspiration pneumonia"
    explanation: Case report documents aspiration pneumonia in LTEC.
  - reference: PMID:32593610
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "He had chronic aspiration, recurrent pneumonia, and a hoarse voice for
      his entire life."
    explanation: Adult case report documents recurrent pneumonia in a laryngeal
      cleft patient.
  - reference: PMID:40227884
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "nearly half (44%) had a history of pneumonia"
    explanation: Cohort study reports frequent pneumonia history in type 1
      laryngeal cleft.
  - reference: PMID:6873110
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "life-threatening disturbances in the form of asphyxia and aspiration
      pneumonia."
    explanation: Review highlights aspiration pneumonia as a major clinical
      complication.
- name: Aspiration pneumonia
  category: Respiratory
  frequency: OCCASIONAL
  description: Aspiration pneumonia due to airway-esophageal communication.
  phenotype_term:
    preferred_term: Aspiration pneumonia
    term:
      id: HP:0011951
      label: Aspiration pneumonia
  evidence:
  - reference: PMID:6873110
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "life-threatening disturbances in the form of asphyxia and aspiration
      pneumonia."
    explanation: Review describes aspiration pneumonia as a key clinical
      disturbance.
- name: Cough
  category: Respiratory
  frequency: OCCASIONAL
  severity: Severe
  description: Chronic or severe cough related to airway communication and
    aspiration.
  phenotype_term:
    preferred_term: Cough
    term:
      id: HP:0012735
      label: Cough
  evidence:
  - reference: PMID:32593610
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "a 56-year-old male referred for hoarseness and chronic cough that was
      discovered to have a type 2 laryngeal cleft."
    explanation: Adult case report documents chronic cough in laryngeal cleft.
  - reference: PMID:39543566
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "severe coughing"
    explanation: Case report describes severe coughing in a child with a
      posterior laryngeal cleft.
  - reference: PMID:40330935
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "All patients experienced cough and choking with feeding."
    explanation: Case series reports cough as a common presenting symptom in
      type 1 laryngeal cleft.
- name: Choking episodes
  category: Respiratory
  frequency: OCCASIONAL
  description: Choking during feeding due to abnormal airway-esophageal
    communication.
  phenotype_term:
    preferred_term: Choking episodes
    term:
      id: HP:0030842
      label: Choking episodes
  evidence:
  - reference: PMID:40330935
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "All patients experienced cough and choking with feeding."
    explanation: Case series documents choking with feeding in type 1 laryngeal
      cleft.
- name: Upper airway obstruction
  category: Respiratory
  frequency: RARE
  description: Obstructive upper airway symptoms can occur even without
    aspiration.
  phenotype_term:
    preferred_term: Upper airway obstruction
    term:
      id: HP:0002781
      label: Upper airway obstruction
  evidence:
  - reference: PMID:37436152
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "the sole presenting feature may be airway obstruction."
    explanation: Case report notes upper airway obstruction as the presenting
      feature in type III clefts without aspiration.
- name: Dysphagia
  category: Gastrointestinal
  frequency: OCCASIONAL
  description: Swallowing dysfunction requiring thickened feeds in some
    patients.
  phenotype_term:
    preferred_term: Dysphagia
    term:
      id: HP:0002015
      label: Dysphagia
  evidence:
  - reference: PMID:37441989
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "children with dysphagia found to have a LC-1 or DIG on endoscopic exam"
    explanation: Study cohort with LC-1/DIG demonstrates dysphagia assessed by
      VFSS.
- name: Stridor
  category: Respiratory
  frequency: RARE
  description: Noisy breathing due to upper airway involvement.
  phenotype_term:
    preferred_term: Stridor
    term:
      id: HP:0010307
      label: Stridor
  evidence:
  - reference: PMID:40330935
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "one had a stridor"
    explanation: Case series reports stridor in a subset of type 1 laryngeal
      cleft patients.
- name: Hoarse voice
  category: Head and Neck
  frequency: OCCASIONAL
  description: Voice changes due to abnormal laryngeal communication.
  phenotype_term:
    preferred_term: Hoarse voice
    term:
      id: HP:0001609
      label: Hoarse voice
  evidence:
  - reference: PMID:32593610
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "referred for hoarseness and chronic cough"
    explanation: Adult case report lists hoarseness as a presenting symptom.
  - reference: PMID:39543566
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "He presented with hoarseness"
    explanation: Pediatric case report notes hoarseness with posterior laryngeal
      cleft.
- name: Dyspnea
  category: Respiratory
  frequency: OCCASIONAL
  severity: Severe
  description: Shortness of breath during feeding or respiratory distress.
  phenotype_term:
    preferred_term: Dyspnea
    term:
      id: HP:0002094
      label: Dyspnea
  evidence:
  - reference: PMID:30783751
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "showed severe dyspnea and dysphagia"
    explanation: Case report documents severe dyspnea in type IV LTEC.
  - reference: PMID:39543566
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "shortness of breath"
    explanation: Case report describes shortness of breath in a child with
      posterior laryngeal cleft.
- name: Wheezing
  category: Respiratory
  frequency: OCCASIONAL
  severity: Severe
  description: Audible wheeze due to airway compromise.
  phenotype_term:
    preferred_term: Wheezing
    term:
      id: HP:0030828
      label: Wheezing
  evidence:
  - reference: PMID:39543566
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "severe wheezing"
    explanation: Case report notes severe wheezing in a child with posterior
      laryngeal cleft.
- name: Aspiration
  category: Respiratory
  frequency: OCCASIONAL
  description: Microaspiration due to abnormal communication between airway and
    esophagus.
  phenotype_term:
    preferred_term: Aspiration
    term:
      id: HP:0002835
      label: Aspiration
  evidence:
  - reference: PMID:40227884
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "can result in chronic microaspiration and subsequent lung disease"
    explanation: Cohort study highlights chronic microaspiration in type 1
      laryngeal cleft.
- name: Atelectasis
  category: Respiratory
  frequency: FREQUENT
  description: Collapse of lung segments noted on chest imaging.
  phenotype_term:
    preferred_term: Atelectasis
    term:
      id: HP:0100750
      label: Atelectasis
  evidence:
  - reference: PMID:40227884
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "atelectasis (56%)"
    explanation: Cohort study reports atelectasis as a common radiographic
      finding in type 1 laryngeal cleft.
- name: Bronchial wall thickening
  category: Respiratory
  frequency: FREQUENT
  description: Bronchial wall thickening observed on chest imaging.
  phenotype_term:
    preferred_term: Bronchial wall thickening
    term:
      id: HP:0033542
      label: Bronchial wall thickening
  evidence:
  - reference: PMID:40227884
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "bronchial wall thickening (59%)"
    explanation: Cohort study reports bronchial wall thickening as a prevalent
      radiographic finding.
diagnosis:
- name: Direct laryngoscopy
  description: Direct laryngoscopy visualizes the interarytenoid region and
    cleft extent.
  diagnosis_term:
    preferred_term: laryngoscopy
    term:
      id: MAXO:0001189
      label: laryngoscopy
  evidence:
  - reference: PMID:38380453
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "direct laryngoscopy/bronchoscopy finally depicts the exact extension
      of the medical condition"
    explanation: Case report highlights direct laryngoscopy as definitive for
      delineating cleft extent.
  - reference: PMID:6873110
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "The diagnosis is made through direct laryngoscopy."
    explanation: Review states that direct laryngoscopy establishes the
      diagnosis.
  - reference: PMID:37816841
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Every patient underwent a diagnostic endoscopy under general anesthesia"
    explanation: Surgical series reports diagnostic endoscopy as a standard
      evaluation step.
- name: Bronchoscopy
  description: Bronchoscopy evaluates the airway and defines the extent of the
    cleft.
  diagnosis_term:
    preferred_term: bronchoscopy
    term:
      id: MAXO:0001183
      label: bronchoscopy
  evidence:
  - reference: PMID:38380453
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "direct laryngoscopy/bronchoscopy finally depicts the exact extension
      of the medical condition"
    explanation: Case report notes bronchoscopy as part of definitive
      evaluation.
  - reference: PMID:30783751
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "We also performed observations with a rigid bronchoscope to assess extent
      of the cleft"
    explanation: Type IV LTEC case used rigid bronchoscopy to assess cleft
      extent.
- name: Chest radiograph imaging
  description: Chest radiographs show pulmonary complications that support
    diagnosis and guide repair.
  diagnosis_term:
    preferred_term: chest radiograph procedure
    term:
      id: MAXO:0010356
      label: chest radiograph procedure
  evidence:
  - reference: PMID:40227884
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Abnormal CXR findings were common (80%), with atelectasis (56%) and
      bronchial wall thickening (59%) being most prevalent."
    explanation: Cohort study documents common abnormal chest radiograph
      findings in type 1 laryngeal cleft.
- name: Flexible endoscopy with sustained pharyngeal inflation
  description: Flexible endoscopy with sustained pharyngeal inflation can
    improve visualization of laryngeal clefts in infants.
  diagnosis_term:
    preferred_term: laryngoscopy
    term:
      id: MAXO:0001189
      label: laryngoscopy
  evidence:
  - reference: PMID:35596199
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "flexible endoscopy with noninvasive ventilation (NIV) and sustained
      pharyngeal inflation (FE-NIV-SPI) in assessing aeroesophageal tracts (AET) to
      facilitate early detection of laryngeal clefts in infants."
    explanation: Study reports FE-NIV-SPI as a technique for early detection of
      laryngeal clefts.
- name: Video fluoroscopic swallow study
  description: Video fluoroscopic swallow study evaluates dysphagia severity and
    guides management of interarytenoid defects.
  diagnosis_term:
    preferred_term: barium swallow radiograph procedure
    term:
      id: MAXO:0035082
      label: barium swallow radiograph procedure
  evidence:
  - reference: PMID:37441989
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Video Fluoroscopic Swallow Study dysphagia severity"
    explanation: Study uses VFSS to characterize dysphagia severity in LC1/DIG
      patients undergoing endoscopic intervention.
  - reference: PMID:6873110
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Radiological demonstration of swallowing and tracheo-oesophagoscopy
      are necessary additional investigations."
    explanation: Review notes radiologic swallow studies as key additional
      investigations.
- name: Computed tomography imaging
  description: Chest CT may be obtained during evaluation but can miss laryngeal
    clefts without targeted endoscopic assessment.
  diagnosis_term:
    preferred_term: computed tomography procedure
    term:
      id: MAXO:0000571
      label: computed tomography procedure
  evidence:
  - reference: PMID:35596199
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "missed by 11 prior bronchoscopy and 5 computer tomography examinations."
    explanation: Case series notes that CT examinations can miss laryngeal
      clefts, underscoring need for targeted endoscopy.
differential_diagnoses:
- name: Esophageal atresia
  description: Prenatal imaging features of LTEC can mimic esophageal atresia.
  disease_term:
    preferred_term: esophageal atresia
    term:
      id: MONDO:0001044
      label: esophageal atresia
  evidence:
  - reference: PMID:30232040
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Laryngotracheoesophageal cleft, a rare differential diagnosis of esophageal
      atresia."
    explanation: Case report highlights LTEC as a differential diagnosis for
      esophageal atresia.
- name: Tracheo-esophageal fistula
  description: Fistulous communication can resemble LTEC and must be
    distinguished.
  disease_term:
    preferred_term: isolated tracheo-esophageal fistula
    term:
      id: MONDO:0018694
      label: isolated tracheo-esophageal fistula
  evidence:
  - reference: PMID:22151899
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Differential diagnoses include tracheo-bronchial fistula, gastro-esophageal
      reflux disease and neurological swallowing disorders, as well as laryngomalacia
      and laryngeal palsy."
    explanation: Review lists tracheo-bronchial fistula among LTEC
      differentials.
- name: Gastroesophageal reflux disease
  description: GERD can present with aspiration and feeding symptoms that
    overlap with LTEC.
  disease_term:
    preferred_term: gastroesophageal reflux disease
    term:
      id: MONDO:0007186
      label: gastroesophageal reflux disease
  evidence:
  - reference: PMID:22151899
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Differential diagnoses include tracheo-bronchial fistula, gastro-esophageal
      reflux disease and neurological swallowing disorders, as well as laryngomalacia
      and laryngeal palsy."
    explanation: Review lists GERD among LTEC differential diagnoses.
- name: Congenital laryngomalacia
  description: Laryngomalacia can cause stridor and aspiration symptoms
    resembling LTEC.
  disease_term:
    preferred_term: congenital laryngomalacia
    term:
      id: MONDO:0007878
      label: congenital laryngomalacia
  evidence:
  - reference: PMID:22151899
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Differential diagnoses include tracheo-bronchial fistula, gastro-esophageal
      reflux disease and neurological swallowing disorders, as well as laryngomalacia
      and laryngeal palsy."
    explanation: Review lists laryngomalacia among LTEC differential diagnoses.
treatments:
- name: Endoscopic laser repair (type 1)
  description: Endoscopic laser repair used for type 1 laryngeal clefts.
  evidence:
  - reference: PMID:40330935
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "endoscopic laser repair remains the gold standard treatment for type
      1 LC."
    explanation: Case series identifies endoscopic laser repair as the standard
      treatment for type 1 laryngeal cleft.
  treatment_term:
    preferred_term: laser surgical procedure
    term:
      id: MAXO:0001578
      label: laser surgical procedure
    qualifiers:
    - predicate:
        preferred_term: surgical procedure
        term:
          id: NCIT:C15329
          label: Surgical Procedure
      value:
        preferred_term: laser surgery
        term:
          id: NCIT:C15268
          label: Laser Surgery
- name: Endoscopic CO2 laser repair (type 3)
  description: Staged endoscopic CO2 laser-assisted repair for type 3 clefts.
  evidence:
  - reference: PMID:40579891
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Nineteen patients with Type III laryngeal clefts who were treated with
      endoscopic carbon dioxide laser-assisted repair were included."
    explanation: Case series reports staged endoscopic CO2 laser repair for type
      3 clefts.
  treatment_term:
    preferred_term: laser surgical procedure
    term:
      id: MAXO:0001578
      label: laser surgical procedure
    qualifiers:
    - predicate:
        preferred_term: surgical procedure
        term:
          id: NCIT:C15329
          label: Surgical Procedure
      value:
        preferred_term: laser surgery
        term:
          id: NCIT:C15268
          label: Laser Surgery
    - predicate:
        preferred_term: therapeutic agent
        term:
          id: NCIT:C2259
          label: Therapeutic Agent
      value:
        preferred_term: carbon dioxide
        term:
          id: NCIT:C65288
          label: Carbon Dioxide
- name: Injection laryngoplasty
  description: Injection laryngoplasty used as a diagnostic or temporizing
    intervention in laryngeal cleft.
  evidence:
  - reference: PMID:39260330
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "LC can be treated surgically by performing suture repair or by Injection
      Laryngoplasty (IL)."
    explanation: Survey study identifies injection laryngoplasty as a treatment
      option for laryngeal cleft.
  - reference: PMID:40330935
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "we initially managed patients with type 1 LC with hyaluronic acid injections
      for a few months"
    explanation: Case series documents injection laryngoplasty used in initial
      management.
  - reference: PMID:35236684
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "injection laryngoplasty is performed safely on an 8-week-old child"
    explanation: Case report supports injection laryngoplasty as a feasible
      intervention in infants.
  treatment_term:
    preferred_term: surgical procedure
    term:
      id: MAXO:0000004
      label: surgical procedure
    qualifiers:
    - predicate:
        preferred_term: therapeutic agent
        term:
          id: NCIT:C2259
          label: Therapeutic Agent
      value:
        preferred_term: hyaluronic acid
        term:
          id: CHEBI:16336
          label: hyaluronic acid
- name: Surgical repair of laryngeal cleft
  description: Operative repair of laryngeal cleft improves aspiration symptoms.
  evidence:
  - reference: PMID:40629707
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "All showed marked improvement after surgical repair."
    explanation: Familial case report shows symptom improvement after surgical
      repair.
  - reference: PMID:6873110
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "an early operative correction of the defect is required."
    explanation: Review emphasizes early operative correction for
      laryngotracheoesophageal cleft.
  - reference: PMID:30783751
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "repair of the cleft was performed by an anterior approach via median
      sternotomy"
    explanation: Type IV case report documents surgical repair of LTEC with an
      anterior approach under ECMO.
  - reference: PMID:35039336
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Simultaneous anterior cervical repair of type IV laryngeal cleft and
      tracheo-oesophageal fistula."
    explanation: Case report demonstrates surgical repair for type IV laryngeal
      cleft with TEF.
  - reference: PMID:32593610
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "successfully treated with an endoscopic approach using absorbable suture"
    explanation: Adult case report supports endoscopic surgical repair.
  - reference: PMID:37073597
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Surgical management in the form of endoscopic Coblation-assisted or
      an open approach is indicated"
    explanation: Tertiary center series supports endoscopic or open surgical
      management for laryngeal cleft.
  treatment_term:
    preferred_term: surgical procedure
    term:
      id: MAXO:0000004
      label: surgical procedure
    qualifiers:
    - predicate:
        preferred_term: surgical procedure
        term:
          id: NCIT:C15329
          label: Surgical Procedure
      value:
        preferred_term: endoscopic procedure
        term:
          id: NCIT:C16546
          label: Endoscopic Procedure
- name: Anterior laryngofissure repair with posterior cartilage grafting
  description: Anterior approach surgical repair with posterior cartilage
    grafting for type III/IV LTEC.
  evidence:
  - reference: PMID:38761217
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "an anterior approach that involved interposition a posterior cartilage
      for Type III or Type IV laryngotracheoesophageal cleft (LTEC)."
    explanation: Surgical series supports anterior laryngofissure repair with
      posterior cartilage grafting for type III/IV LTEC.
  treatment_term:
    preferred_term: surgical procedure
    term:
      id: MAXO:0000004
      label: surgical procedure
- name: Combined open and endoscopic repair for long clefts
  description: Combined open and endoscopic approaches may be required for long
    clefts with tracheal extension.
  evidence:
  - reference: PMID:37816841
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "Primary and revision repair of long clefts with tracheal extension may
      require a combined approach."
    explanation: Series reports use of combined open and endoscopic approaches
      for long clefts.
  treatment_term:
    preferred_term: surgical procedure
    term:
      id: MAXO:0000004
      label: surgical procedure
biochemical: []
genetic:
- name: SOX2
  association: Associated
  evidence:
  - reference: DOI:10.1038/s41598-024-53098-w
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: "FOXF1, FOXC1, and FOXD1, as well as the SRY-box transcription factor,
      SOX2, demonstrate the most significant preferential expression in both mouse
      and human embryos."
    explanation: Single-cell analysis links SOX2 to esophageal malformation gene
      expression patterns.
  gene_term:
    preferred_term: SOX2
    term:
      id: hgnc:11195
      label: SOX2
- name: FOXF1
  association: Associated
  evidence:
  - reference: DOI:10.1038/s41598-024-53098-w
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: "FOXF1, FOXC1, and FOXD1, as well as the SRY-box transcription factor,
      SOX2, demonstrate the most significant preferential expression in both mouse
      and human embryos."
    explanation: Single-cell analysis highlights FOXF1 among genes enriched in
      esophageal malformation contexts.
  gene_term:
    preferred_term: FOXF1
    term:
      id: hgnc:3809
      label: FOXF1
- name: FOXC1
  association: Associated
  evidence:
  - reference: DOI:10.1038/s41598-024-53098-w
    supports: SUPPORT
    evidence_source: COMPUTATIONAL
    snippet: "FOXF1, FOXC1, and FOXD1, as well as the SRY-box transcription factor,
      SOX2, demonstrate the most significant preferential expression in both mouse
      and human embryos."
    explanation: Single-cell analysis highlights FOXC1 among genes enriched in
      esophageal malformation contexts.
  gene_term:
    preferred_term: FOXC1
    term:
      id: hgnc:3800
      label: FOXC1
- name: RERE
  association: Associated
  evidence:
  - reference: PMID:30245899
    supports: SUPPORT
    evidence_source: HUMAN_CLINICAL
    snippet: "a 1p36 deletion including the RERE gene was detected."
    explanation: Case report identifies a 1p36 deletion including RERE in a
      neonate with type IV LTEC.
  gene_term:
    preferred_term: RERE
    term:
      id: hgnc:9965
      label: RERE
environmental: []
datasets: []
clinical_trials: []
references:
- reference: DOI:10.1186/s13023-024-03106-z
  title: 'Tracheal agenesis versus tracheal atresia: anatomical conditions, pathomechanisms
    and causes with a possible link to a novel MAPK11 variant in one case'
  findings: []
- reference: DOI:10.3389/fcell.2022.1022457
  title: Lung epithelium development and airway regeneration
  findings: []