Congenital heart disease is the most common form of birth defect, affecting approximately 1% of liveborn babies. Secundum atrial septal defect (ASD) is the second most common form of congenital heart disease (CHD). Most cases have no known cause. Chromosomal, syndromal and teratogenic causes account for a minority of cases. The hypothesis that mutations in the ASD genes NKX2-5 and GATA4 may cause apparently sporadic ASD was tested by sequencing them in unrelated probands with ASD. In this study, 1/102 individuals with ASD had an NKX2-5 mutation, and 1/129 had a deletion of the GATA4 gene. The cardiac transcription factor TBX20 interacts with other ASD genes but had not previously been associated with human disease. Of 352 individuals with CHD, including 175 with ASD, 2 individuals, each with a family history of CHD, had pathogenic mutations in TBX20. Phenotypes included ASD, VSD, valvular abnormalities and dilated cardiomyopathy. These studies of NKX2-5, GATA4 and TBX20 indicate that dominant ASD genes account for a small minority of cases of ASD, and emphasize the considerable genetic heterogeneity in dominant ASD (also caused by mutations in MYH6 and ACTC). A new syndrome of dominant ASD and the Marcus Gunn jaw winking phenomenon is reported. Linkage to known loci was excluded, extending this heterogeneity, but a whole genome scan did not identify a candidate locus for this disorder. Previous studies of inbred laboratory mice showed an association between patent foramen ovale (PFO) and measures of atrial septal morphology, particularly septum primum length (???flap valve length??? or FVL). In humans, PFO is associated with cryptogenic stroke and migraine, and is regarded as being in a pathological contiuum with ASD. Twelve inbred strains, including 129T2/SvEms and QSi5, were studied, with generation of [129T2/SvEms x QSi5] F1, F2 and F14 mice. Studies of atrial morphology in 3017 mice confirmed the relationship between FVL and PFO but revealed considerable complexity. An F2 mapping study identified 7 significant and 6 suggestive quantitative trait loci (QTL), affecting FVL and two other traits, foramen ovale width (FOW) and crescent width (CRW). Binary analysis of PFO supported four of these.

Thesis (M. Sc.)--University of Hong Kong, 2001. / Includes bibliographical references (leaves 68-75).

Thesis--University of Kentucky (M.S.), 2003. / Title from document title page. Document formatted into pages; contains viii, 86 p. : ill. Includes abstract and vita. Includes bibliographical references (p. 82-85).

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine. / Purpose: Infants born with Heterotaxy Syndrome (HS) often have intestinal malrotation in addition to severe congenital heart disease (CHD). Given the catastrophic risk of midgut volvulus, where the vascular supply to the gut is cut off causing necrotic bowel and possible future short‐gut syndrome following surgery, an elective Ladd procedure is recommended at the first diagnosis of malrotation. In patients with severe CHD, however, the risk of complications from prophylactic surgery is high, especially in infancy prior to stable cardiac palliation. This study sought to determine whether deferring a Ladd procedure during the first six months of life in infants with CHD is safe by focusing on the incidence of volvulus in the HS population, morbidity of volvulus and morbidity of an elective Ladd procedure. Methods: Medical records of patients with HS and intestinal malrotation at Phoenix Children’s Hospital from 2006‐2011 were reviewed. Stage of heart surgery, severity of heart disease, diagnosis of intestinal malrotation, and timing of Ladd procedure if applicable were recorded. Results: 31 patients with HS and intestinal malrotation were identified. Of the 31, 9 had a Ladd procedure prior to six months of age, 2 for volvulus and the other 7 either electively or for less severe GI symptoms that were not suggestive of volvulus. The other 22 did not have a Ladd procedure prior to six months of age. There was one death (1/22) from a non‐gastrointestinal cause in a patient who had not undergone a Ladd procedure. There were no deaths in the 9 patients who underwent a Ladd procedure (0/9). Conclusions: Given the low overall incidence of volvulus in HS, and with continued vigilance for obstructive symptoms, this study suggests that delaying the Ladd procedure in asymptomatic patients with HS and CHD and intestinal malrotation is safe. Watchful waiting may reduce the incidence of cardiac complications during the Ladd procedure by allowing for stabilizing cardiac surgical palliation prior to elective abdominal surgery.

Congenital heart disease is the most common form of birth defect, affecting approximately 1% of liveborn babies. Secundum atrial septal defect (ASD) is the second most common form of congenital heart disease (CHD). Most cases have no known cause. Chromosomal, syndromal and teratogenic causes account for a minority of cases. The hypothesis that mutations in the ASD genes NKX2-5 and GATA4 may cause apparently sporadic ASD was tested by sequencing them in unrelated probands with ASD. In this study, 1/102 individuals with ASD had an NKX2-5 mutation, and 1/129 had a deletion of the GATA4 gene. The cardiac transcription factor TBX20 interacts with other ASD genes but had not previously been associated with human disease. Of 352 individuals with CHD, including 175 with ASD, 2 individuals, each with a family history of CHD, had pathogenic mutations in TBX20. Phenotypes included ASD, VSD, valvular abnormalities and dilated cardiomyopathy. These studies of NKX2-5, GATA4 and TBX20 indicate that dominant ASD genes account for a small minority of cases of ASD, and emphasize the considerable genetic heterogeneity in dominant ASD (also caused by mutations in MYH6 and ACTC). A new syndrome of dominant ASD and the Marcus Gunn jaw winking phenomenon is reported. Linkage to known loci was excluded, extending this heterogeneity, but a whole genome scan did not identify a candidate locus for this disorder. Previous studies of inbred laboratory mice showed an association between patent foramen ovale (PFO) and measures of atrial septal morphology, particularly septum primum length (???flap valve length??? or FVL). In humans, PFO is associated with cryptogenic stroke and migraine, and is regarded as being in a pathological contiuum with ASD. Twelve inbred strains, including 129T2/SvEms and QSi5, were studied, with generation of [129T2/SvEms x QSi5] F1, F2 and F14 mice. Studies of atrial morphology in 3017 mice confirmed the relationship between FVL and PFO but revealed considerable complexity. An F2 mapping study identified 7 significant and 6 suggestive quantitative trait loci (QTL), affecting FVL and two other traits, foramen ovale width (FOW) and crescent width (CRW). Binary analysis of PFO supported four of these.

Thesis (M.A.)--Northern Kentucky University, 2007. / Made available through ProQuest. Publication number: AAT 1447123. ProQuest document ID: 1414126941. Includes bibliographical references (p. 30-31)

Thesis (M.Med.Sc.)--University of Hong Kong, 2002. / Includes bibliographical references (leaves 25-30). Also available in print.

OBJECTIVES: Congenital heart disease or CHD is a condition that affects 8 out of every 1,000 newborns. Every year more than 35,000 newborns are diagnosed with a congenital heart disease in the United States. Neonates and children with congenital heart disease are at increased risk for thrombotic events, especially those with a single ventricle physiology. The objective of this study was to assess the incidence and to identify the predictors of thrombosis in neonates and children with surgical and non-surgical heart diseases. METHODS: We performed a retrospective analysis of the Health Care and Cost Use Project Kid’s Inpatient Database. Neonates and children with a congenital heart disease were identified using the international classification of disease, 9th revision, clinical modification (ICD-9 CM) diagnostic codes, and grouped into two sub-categories of surgical heart and non-surgical heart diseases. These groups were further divided into four types of lesions: septal defects, single ventricle physiology, right ventricle outflow tract obstruction, and left ventricle outflow tract obstruction. Demographic characteristics, the presence of co-morbidities, the incidence of any thrombotic events, mortality rate, and the presence of additional complications such as acute kidney injury, sepsis, neurologic complications, the need for extracorporeal membrane oxygenation or ventricular assist device were also collected using ICD-9 CM codes. After propensity-matched analysis, neonates and children with a surgical congenital heart disease were compared with those with a non-surgical heart disease. We used uni- and multivariable logistic regression analysis to identify the predictors associated with the incidence of thrombotic events in both sub-group. RESULTS: In children with surgical heart disease, the incidence of thrombosis was 3.90%, compared with 2.13% in children with non-surgical heart disease. Furthermore, those with single ventricle physiology (surgical 2.13%; non-surgical 3.41%) or right ventricle outflow tract obstruction (surgical 1.54%; non-surgical 1.66) had the highest incidence of thrombosis. In addition to demographic characteristics (e.g. age) and the type of congenital heart disease, we observed that extracorporeal membrane oxygenation (ECMO) or ventricular assist device(VAD), the presence acute kidney injury, sepsis, and coagulopathy were strong predictors for the development of thrombotic events. CONCLUSIONS: Children with both surgical and non-surgical heart disease have an increased risk for thrombotic events, but those with a single ventricle physiology or a right ventricle outflow tract obstruction had a further increased risk.

Background: Children with congenital heart disease (CHD) often face barriers unique to their diagnoses, making participation in community physical activity programs difficult. This pilot, feasibility study evaluated the appropriateness (i.e. feasibility and enjoyment ) of the Sportball program among a group of children with CHD. This study also sought to observe any changes in physical literacy outcomes and to explore physical activity perceptions of participants, in order to better inform the future use of community-based interventions for this population. Methods: This study employed a mixed-methods evaluation of a 10-week community-based intervention. Data from two focus groups (baseline and post-intervention) and field notes after each intervention session were collected. Physical literacy outcomes were determined using the Canadian Assessment of Physical Literacy. Results: Participants with CHD (n=9) successfully participated in Sportball, as demonstrated by the ability of all participants to complete program activities, participants’ overall enjoyment of the program and fair attendance (approximately 80% of intervention sessions). Improvements in motor skill and torso strength were observed, with a statistically significant difference (p < 0.01) in motor skill classification. Participation in Sportball facilitated positive social interactions during sport and was influenced by personal, social and environmental factors. Conclusion: Overall, participation in Sportball is appropriate for children with CHD who may have motor development delays and/or activity restrictions.