Dyskinesia, Heterotaxy and Congenital Heart Disease
Dyskinesia, Heterotaxy and 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....
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.
-  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.