Dyskinesia, Heterotaxy and Congenital Heart Disease
| Status: | Completed |
|---|---|
| Conditions: | Cardiology |
| Therapuetic Areas: | Cardiology / Vascular Diseases |
| Healthy: | No |
| Age Range: | 2 - Any |
| Updated: | 4/21/2016 |
| Start Date: | January 2008 |
| End Date: | October 2011 |
Ciliary Dysfunction as an Underlying Etiology Linking Primary Ciliary Dyskinesia With Heterotaxy and Complex Congenital Heart Disease
This study will examine genetic material obtained from blood and tissue samples of patients
with congenital heart disease (CHD) and heterotaxy (an abnormality in the left-right
positioning of organs in the body, also called situs inversus) to gain a better
understanding of these disorders and of a lung disease called primary ciliary dyskinesia
(PCD). CHD is prevalent in patients with heterotaxy. It is believed that certain forms of
CHD or heterotaxy may have the same genetic origin as PCD.
Individuals 2 years of age or older who have a CHD or heterotaxy or both may be eligible for
this study. Participants undergo some or all of the following tests and procedures:
- Blood tests, electrocardiogram (EGC) and chest x-ray.
- Saliva collection: Subjects rinse their mouth with water, and then spit approximately
1.5 cc of saliva into a sterile container.
- Buccal swabs: A small soft, toothbrush-like swab is rubbed on the inside lining of the
cheek to collect tissue samples.
- Nasal tests to measure nasal nitric oxide levels and to obtain tissue samples from the
inside of the nostrils: For the nitric oxide level test, a rubber probe is inserted
into one of the nostrils until it fits snugly and comfortably. The subject then takes a
deep breath and then exhales all the way out through the mouth through a plastic
device. During exhalation, gas measurements are recorded on a computer. To obtain
tissue samples, a device is inserted in a nostril and scraped gently against the inside
of the nose.
- Echocardiography: This ultrasound test of the heart uses sound waves to obtain pictures
of the heart. A small wand with a warm clear gel is moved around the chest to obtain
the images.
- Abdominal ultrasound: This ultrasound test of the heart uses sound waves to obtain
pictures of the abdominal organs. A small wand with a warm clear gel is moved around
the abdomen to obtain the images....
with congenital heart disease (CHD) and heterotaxy (an abnormality in the left-right
positioning of organs in the body, also called situs inversus) to gain a better
understanding of these disorders and of a lung disease called primary ciliary dyskinesia
(PCD). CHD is prevalent in patients with heterotaxy. It is believed that certain forms of
CHD or heterotaxy may have the same genetic origin as PCD.
Individuals 2 years of age or older who have a CHD or heterotaxy or both may be eligible for
this study. Participants undergo some or all of the following tests and procedures:
- Blood tests, electrocardiogram (EGC) and chest x-ray.
- Saliva collection: Subjects rinse their mouth with water, and then spit approximately
1.5 cc of saliva into a sterile container.
- Buccal swabs: A small soft, toothbrush-like swab is rubbed on the inside lining of the
cheek to collect tissue samples.
- Nasal tests to measure nasal nitric oxide levels and to obtain tissue samples from the
inside of the nostrils: For the nitric oxide level test, a rubber probe is inserted
into one of the nostrils until it fits snugly and comfortably. The subject then takes a
deep breath and then exhales all the way out through the mouth through a plastic
device. During exhalation, gas measurements are recorded on a computer. To obtain
tissue samples, a device is inserted in a nostril and scraped gently against the inside
of the nose.
- Echocardiography: This ultrasound test of the heart uses sound waves to obtain pictures
of the heart. A small wand with a warm clear gel is moved around the chest to obtain
the images.
- Abdominal ultrasound: This ultrasound test of the heart uses sound waves to obtain
pictures of the abdominal organs. A small wand with a warm clear gel is moved around
the abdomen to obtain the images....
The goal of this study is to elucidate the possible role of primary ciliary dyskinesia (PCD)
in complex congenital heart disease associated with heterotaxy. This study arises from our
recent finding of an unexpectedly high incidence (40 percent) of complex congenital heart
disease together with heterotaxy in a mutant mouse model of PCD. These findings suggest
heterotaxy can arise from mutations causing PCD. Consistent with this, a recent clinical
research study showed some patients with PCD have undiagnosed heterotaxy. However, there has
not been any clinical study to ascertain if patients diagnosed with heterotaxy may suffer
from PCD, the focus of this IRB protocol. These studies are of immediate clinical
importance, as heterotaxy patients undergoing surgical correction for complex structural
heart defects can become ventilator dependent for unknown causes. A diagnosis of PCD in
patients with heterotaxy would significantly alter clinical management strategies that have
the potential to significantly improve outcome for heterotaxy patients undergoing high-risk
cardiac surgery for complex congenital heart defects.
For this study, we will recruit pediatric subjects undergoing surgery for complex congenital
heart defects associated with heterotaxy at Children's National Medical Center. We will also
recruit adult patients with heterotaxy heart disease or situs inversus from the Children's
National Medical Center and at NIH. In addition, we will recruit patients, ages 2 years and
older, seen at the NIH by Dr. Kenneth Olivier with known PCD or Kartagener syndrome and with
documentation or high clinical suspicion of heterotaxy or situs inversus into our study.
Subjects will be evaluated for PCD using standard operating procedures (SOPs). This will
include obtaining airway epithelial tissue samples to assess ciliary motion by
videomicroscopy and for assessing defects in ciliary ultrastructure by electron microscopy.
In addition, nasal nitric oxide measurements will be obtained, as reduced NO levels are
often associated with PCD. All of these procedures will utilize SOPs obtained from approved
IRB protocols that are part of a multi-center study at the University of North Carolina (Dr.
Michael Knowles) and at the NIH (Dr. Ken Olivier, NIAID). In addition, blood, buccal swab,
and saliva samples will be obtained for DNA analysis of candidate genes known to cause
heterotaxy and/or PCD. Through these studies, we hope to establish whether mutations causing
PCD may contribute to heterotaxy and situs anomalies. Such findings may suggest changes in
the standard of care for heterotaxy patients to include the evaluation for PCD, particularly
prior to surgery. In addition, the DNA analysis may provide novel insights into the genetic
causes for complex congenital heart defects associated with heterotaxy and PCD, allowing the
future development of appropriate diagnostic tests for more accurate identification of
patients at risk for PCD. Together, the outcome of this study can have significant impact on
improving the clinical care for patients with congenital heart disease associated with situs
anomalies.
in complex congenital heart disease associated with heterotaxy. This study arises from our
recent finding of an unexpectedly high incidence (40 percent) of complex congenital heart
disease together with heterotaxy in a mutant mouse model of PCD. These findings suggest
heterotaxy can arise from mutations causing PCD. Consistent with this, a recent clinical
research study showed some patients with PCD have undiagnosed heterotaxy. However, there has
not been any clinical study to ascertain if patients diagnosed with heterotaxy may suffer
from PCD, the focus of this IRB protocol. These studies are of immediate clinical
importance, as heterotaxy patients undergoing surgical correction for complex structural
heart defects can become ventilator dependent for unknown causes. A diagnosis of PCD in
patients with heterotaxy would significantly alter clinical management strategies that have
the potential to significantly improve outcome for heterotaxy patients undergoing high-risk
cardiac surgery for complex congenital heart defects.
For this study, we will recruit pediatric subjects undergoing surgery for complex congenital
heart defects associated with heterotaxy at Children's National Medical Center. We will also
recruit adult patients with heterotaxy heart disease or situs inversus from the Children's
National Medical Center and at NIH. In addition, we will recruit patients, ages 2 years and
older, seen at the NIH by Dr. Kenneth Olivier with known PCD or Kartagener syndrome and with
documentation or high clinical suspicion of heterotaxy or situs inversus into our study.
Subjects will be evaluated for PCD using standard operating procedures (SOPs). This will
include obtaining airway epithelial tissue samples to assess ciliary motion by
videomicroscopy and for assessing defects in ciliary ultrastructure by electron microscopy.
In addition, nasal nitric oxide measurements will be obtained, as reduced NO levels are
often associated with PCD. All of these procedures will utilize SOPs obtained from approved
IRB protocols that are part of a multi-center study at the University of North Carolina (Dr.
Michael Knowles) and at the NIH (Dr. Ken Olivier, NIAID). In addition, blood, buccal swab,
and saliva samples will be obtained for DNA analysis of candidate genes known to cause
heterotaxy and/or PCD. Through these studies, we hope to establish whether mutations causing
PCD may contribute to heterotaxy and situs anomalies. Such findings may suggest changes in
the standard of care for heterotaxy patients to include the evaluation for PCD, particularly
prior to surgery. In addition, the DNA analysis may provide novel insights into the genetic
causes for complex congenital heart defects associated with heterotaxy and PCD, allowing the
future development of appropriate diagnostic tests for more accurate identification of
patients at risk for PCD. Together, the outcome of this study can have significant impact on
improving the clinical care for patients with congenital heart disease associated with situs
anomalies.
- INCLUSION CRITERIA:
Patients who have diagnosed congenital heart disease, heterotaxy or situs inversus will be
asked to participate in this study regardless of sex, age, or race. In addition, patients
who have diagnosed PCD or Kartagener syndrome with documentation or high clinical
suspicion of heterotaxy or situs inversus will also be recruited to participate in this
study. There is no known ethnic or racial predilection for heterotaxy, congenital heart
disease, situs inversus, PCD, or Kartagener syndrome.
EXCLUSION CRITERIA:
Certain conditions may preclude specific procedures included in this protocol, but may
still allow pertinent parts of the diagnostic evaluation. These conditions/procedures may
include: pregnancy/chest radiograph. For reversible conditions, such as acute upper airway
infection, significant epistaxis within the prior week (not related to number 2 below), or
lower airway infection with uncontrollable coughing, the participant may need to be
re-evaluated after resolution. For nasal NO or nasal mucosal scrapings, the following
lists the absolute contraindications:
1. Anatomic abnormality of the nose or sinuses (e.g. complete sinus blockage or
turbinatectomy) that precludes the measurement of nasal NO.
2. A severe bleeding diathesis or condition, such as hereditary hemorrhagic
telangiectasia syndrome, that may predispose to significant nasal bleeding or result
in a severely excoriated nasal mucosa.
We found this trial at
2
sites
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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111 Michigan Ave NW
Washington, District of Columbia
Washington, District of Columbia
(202) 476-5000
Childrens National Medical Center As the nation’s children’s hospital, the mission of Children’s National Medical...
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