To delineate specific clinical phenotypic features among kindreds with an affected heterotaxy syndrome and compare differences, both within in each pair, and among the entire cohort.
To compare the wild-type genotype of unaffected parents or siblings with an affected family member and determine which genotypic differences contribute to phenotypic variability among the kindreds.
To identify, through exome and RNA sequencing, causative genes and modifier genes, that contribute to the observed phenotypic differences
To identify the differences in RNA expression between parent-child pairs and amongst the family as a whole.
To identify clinical short- and long-term (5-year) outcomes among our initial cohort
One of the most serious congenital malformation types associated with Heterotaxy is congenital heart disease. Congenital heart disease of all types is the most common birth defect in the general population, affecting approximately 1.5/100 newborns, and is the leading cause of death in infants.
We propose to perform exome and RNA sequencing on a group of patients with Heterotaxy syndrome followed at PCH, for the purpose of new genes that may be causative for the disorder. Our research project will expand the knowledge of genetic mechanisms in human heterotaxy syndromes.
Our research proposal will also investigate the short and long –term (5 year) clinical correlates of genetic and phenotypic variants in heterotaxia. Among this initial cohort, we will describe the clinical course and outcomes and determine whether specific identified genetic or phenotypic patterns are associated with adverse outcomes, including death, re-intervention or re-admission, prolonged hospital length of stay, or other major complications.
Basic Eligibility Criteria:
Males and females with Heterotaxy syndrome (via accepted right/left sidedness
criteria) or an affected direct relative of patient with Heterotaxy syndrome
Participant consent or parental/guardian consent and participant assent
Participant fluent in English or Spanish
Emergent, life threatening condition impacting study conduct
In the opinion of the primary care physician or principal investigator, the subject
is likely to be non-compliant with the study protocol
For females: Pregnancy at the time of study visit
Phoenix Children’s Hospital
Tabitha Moe, MD.