Comprehensive Phenotypic and Genetic Assessment of Tracheal and Esophageal Birth Defects in Patients
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Tracheoesophageal Fistula
- Sponsor
- Children's Hospital Medical Center, Cincinnati
- Enrollment
- 360
- Locations
- 1
- Primary Endpoint
- Anatomic phenotypes using MRI
- Status
- Recruiting
- Last Updated
- 3 years ago
Overview
Brief Summary
The investigators propose a preliminary study performing exome sequencing on samples from patients and their biologically related family members with tracheal and esophageal birth defects (TED). The purpose of this study is to determine if patients diagnosed with TED and similar disorders carry distinct mutations that lead to predisposition.
The investigators will use advanced, non-invasive magnetic resonance imaging (MRI) techniques to assess tracheal esophageal, lung, and cardiac morphology and function in Neonatal Intensive Care Unit (NICU) patients. MRI techniques is done exclusively if patient is clinically treated at primary study location and if patient has not yet had their initial esophageal repair.
Detailed Description
TEDs (tracheal esophageal birth defects) are a life threatening congenital disorder with multiple long term complications. Occurring in 1 in 2,500 to 4,500 live births, TEDs include tracheal malformations such as tracheomalacia, laryngotracheoesophageal clefts, tracheal agenesis, tracheal stenosis, tracheal bronchus, esophageal bronchus and esophageal malformations such as esophageal atresia (EA), tracheal esophageal fistula (TEF), and esophageal duplication. TEDs likely have a genetic basis, but in most cases the specific mutations are unknown. The most commonly diagnosed TED, requiring neonatal hospitalization, is EA/TEF. The familial recurrence rate of EA/TEF is 1% suggesting many result from de novo mutations and while environmental factors may have a minor influence, the mechanisms are unclear. The investigators hypothesize that patients diagnosed with TED and similar disorders carry distinct mutations that lead to predisposition. Currently the diagnosis is confirmed only with a plain chest x-ray showing a coiled feeding tube within the upper esophageal pouch. This approach does not determine the anatomic subtype of EA/TEF, the number or location of TEFs, the size of the gap between proximal and distal esophagus, or the presence of tracheomalacia. Many have evaluated preoperative laryngotracheo-bronchoscopy (LTB) and others have evaluated preoperative computerized tomography (CT) scanning to decrease the unknown factors associated with x-ray, but despite their potential benefits, they have great drawbacks. Therefore, there is a compelling need to develop noninvasive non ionizing imaging methods to evaluate TED infants. Magnetic Resonance Imaging (MRI) is an ideal candidate to fill this role in that it provides non-invasive high resolution anatomic and functional information. Here the investigators propose a preliminary study performing exome sequencing on samples from these patients and their biologically related family members. The investigators will also use advanced, non-invasive MR imaging techniques to assess TE, lung, and cardiac morphology and function in NICU patients.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patient that has been diagnosed by clinical team with a congenital TED OR family member to the TED diagnosed patient.
- •Willingness to donate biological specimens.
- •Ability to consent/assent as appropriate.
Exclusion Criteria
- •Unable to determine or unavailable parent trio.
- •Unable to provide DNA sample.
- •Inability to provide consent.
- •NICU TED Genetic Cohort:
- •Inclusion Criteria:
- •Infant born between 24 and 42 weeks PMA.
- •TED diagnosed by clinical team.
- •Inpatient in the Neonatal Intensive Care Unit (NICU) OR family member to the inpatient in the NICU.
- •Willingness to donate biological specimens.
- •Ability to consent/assent as appropriate.
Outcomes
Primary Outcomes
Anatomic phenotypes using MRI
Time Frame: 1 day
Investigate the esophageal, tracheal, mediastinal and pulmonary anatomy in patients with TEDs.
Genomic Sequencing
Time Frame: 1 day
Identify novel genes and mutations in patients with TEDs using trio genomic sequencing of TED patients and their parents.
Secondary Outcomes
- Change in the anatomic phenotype using MRI(Change in MRI from pre-repair to discharge)