The Sequencing for Detection in Congenital Heart Disease (SD-CHD) Study
Scripps Translational Science Institute
Summary
This study is enrolling pregnant persons treated at Rady Children's Hospital fetal cardiology program with a prenatal diagnosis of congenital heart disease to look for genetic disorders in the fetus or unborn baby. Congenital heart disease (CHD) is a group of structural differences to the heart that represent the most common birth defect among liveborn infants world-wide. CHD is the leading cause of birth-defect associated infant death. Prenatal detection allows for delivery planning, postnatal repair, specialized medications, and detailed counseling for parents. Up to one in three fetuses with CHD may have a genetic cause. In babies, knowing about genetic diseases helps patients and doctors provide the best care for their babies. If identified prenatally, this same knowledge may help participants prepare for their location of delivery, meet with specialists, and consider specialized treatments and medications that may be appropriate. The diagnostic yield and clinical utility of whole genome sequencing (WGS) in fetuses with prenatally detected congenital heart disease (CHD) will be compared to routine clinical testing in patients choosing amniocentesis or chorionic villus sampling. DNA will be obtained from fetal samples and biological parent blood samples and analyzed according to standard clinical interpretation guidelines. Results will be reported to healthcare providers and patients and measures of clinical utility will be collected. Additionally, measures of stress, anxiety, depression, and perceived utility of information will be assessed by validated survey tools. A historical cohort of patients electing for diagnostic procedures will be used as a comparison population.
Description
Many genetic causes of CHD are missed by standard microarray and karyotype. Whole genome sequencing (WGS) and other specialized technologies for genetic and epigenetic diagnosis such as long-read sequencing, digital droplet PCR, RNA sequencing, and methylation analysis will identify additional causes of CHD but these technologies have not been systematically offered to patients prenatally. Precision fetal diagnosis has expanded from diagnosis of aneuploidy on karyotype to copy number variants detected on microarray (such as 22q11 deletion syndrome) to gene sequencing through gene panels and e…
Eligibility
- Age range
- 18+ years
- Sex
- Female
- Healthy volunteers
- No
Inclusion Criteria: * Pregnant individual with ongoing pregnancy with prenatally detected fetal CHD * Desire for genetic diagnosis and clinical plan for amniocentesis or chorionic villus sampling Exclusion Criteria: * Gestational age of 38 weeks or greater * Clinical course entirely explained by known chromosomal abnormality or confirmed genetic diagnosis that explains the clinical condition * Pregnant persons under 18 years of age
Interventions
- Diagnostic TestWhole Genome Sequencing (WGC) from subject samples
Perform whole genome sequencing (WGS) on fetuses with prenatally detected congenital heart disease (CHD) who meet inclusion criteria. Assess diagnostic yield of WGS in CHD and effect of prenatal versus postnatal phenotype on diagnostic yield.
Location
- Rady Children's Institute for Genomic MedicineSan Diego, California