Phenotypic and Genetic Assessment of Tracheal and Esophageal Birth Defects in Patients
| Status: | Recruiting |
|---|---|
| Conditions: | Hospital, Women's Studies, Gastrointestinal, Pulmonary |
| Therapuetic Areas: | Gastroenterology, Pulmonary / Respiratory Diseases, Other, Reproductive |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 3/23/2019 |
| Start Date: | March 28, 2018 |
| End Date: | January 2024 |
| Contact: | Paul Kingma, MD, PhD |
| Email: | paul.kingma@cchmc.org |
| Phone: | (513)636-2995 |
Comprehensive Phenotypic and Genetic Assessment of Tracheal and Esophageal Birth Defects in Patients
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 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. The purpose of this study is to determine if
patients diagnosed with TED and similar disorders carry distinct mutations that lead to
predisposition and to determine if an MRI is a more effective way of evaluating the TEDs.
patients and their biologically related family members with tracheal and esophageal birth
defects (TED). 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. The purpose of this study is to determine if
patients diagnosed with TED and similar disorders carry distinct mutations that lead to
predisposition and to determine if an MRI is a more effective way of evaluating the TEDs.
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.
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.
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.
Exclusion Criteria:
- Unable to determine or unavailable parent trio.
- Unable to provide DNA sample.
- Inability to provide consent.
NICU TED MRI Cohort:
Inclusion Criteria:
- Infant born between 24 and 42 weeks PMA.
- TED diagnosed by clinical team.
- Inpatient in the CCHMC (Cincinnati Children's Hospital Medical Center) NICU.
- Clinically stable and adequate temperature control to tolerate MRI as determined by
the primary clinical team.
- Infant and biological parents are participating in the NICU TED cohort.
- Ability to consent/assent as appropriate.
Exclusion Criteria:
- Infant is on extracorporeal membrane oxygenation (ECMO).
- Evidence of congenital diseases that may affect ability to tolerate MRI.
- Standard MRI exclusion criteria as set forth by the CCHMC Department of Radiology.
This includes any contraindications from tracheostomy tubes that are not MR
compatible.
- Inability to provide consent.
TED Genetic Cohort:
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 Control MRI Cohort:
Inclusion Criteria:
- Infant born between 24 and 42 weeks post menstrual age (PMA).
- No tracheal or esophageal defects.
- Inpatient in the CCHMC NICU.
- Clinically stable and adequate temperature control to tolerate MRI as determined by
the primary clinical team.
Exclusion Criteria:
- Infant is on ECMO.
- Evidence of congenital diseases that may affect ability to tolerate MRI.
- Standard MRI exclusion criteria as set forth by the CCHMC Department of Radiology.
This includes any contraindications from tracheostomy tubes that are not MR
compatible.
- Inability to provide consent.
We found this trial at
1
site
Cincinnati, Ohio 45229
Principal Investigator: Paul Kingma, MD, PhD
Phone: 513-636-2995
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