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Whole Exome Sequencing and Whole Genome Sequencing for Nonimmune Fetal/Neonatal Hydrops

ConditionsNonimmune Fetal HydropsNonimmune Hydrops in NeonateGenetic Disorders
Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age16-55
SponsorThomas Jefferson University

About this trial

Brief Summary: Nonimmune hydrops fetalis (NIHF) is a potentially fatal condition characterized by abnormal fluid accumulation in two or more fetal compartments. Numerous etiologies may lead to NIHF, and the underlying cause often remains unclear (1). The current standard of genetic diagnostic testing includes a fetal karyotype and chromosomal microarray (CMA), with an option to pursue single gene testing on amniocytes collected by amniocentesis (2). A large subgroup of the NIHF causes includes single gene disorders that are not diagnosed with the standard genetic workup for hydrops. Currently, nearly 1 in 5 cases of NIHF is defined as idiopathic, meaning there is no identified etiology (2). The investigators believe this is because the causes of NIHF are not completely investigated, specifically single gene disorders. Our research study aims to increase the diagnostic yield by performing whole exome sequencing (WES) and whole genome sequencing (WGS) on prenatal and neonatal NIHF cases when standard genetic testing is negative, identifying known and new genes, thus providing vital information to families regarding the specific diagnosis and risk to future pregnancies. The investigators plan to perform WES as the initial diagnostic test. If WES is negative, then the investigators will proceed to perform WGS.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Fetal hydrops identified anytime in pregnancy after the first trimester

Parents are planning to proceed with amniocentesis as a routine workup for hydrops.

Both parents are available for blood sample collection

Normal CMA and normal karyotype if performed

Disqualifiers

Microarray was abnormal or karyotype was abnormal

Hydrops caused by congenital infection

Fetomaternal hemorrhage was a documented etiology for hydrops

Parental DNA cannot be obtained for either parents

Trial population

Patients will be recruited from MFM physicians, paediatricians,and neonatologists.

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

  • Whole Exome Sequencing

    Diagnostic test

    Whole exome sequencing (WES) provides more detailed information through greater resolution, identifying single base-pair changes and small insertions and deletions. WES performs sequencing on the protein-coding exons, which are contained in 1-2% of the genome but make up over 85% of all known pathogenic mutations.

  • Whole Genome Sequencing

    Diagnostic test

    Whole Genome Sequencing (WGS) has emerged in recent years as a diagnostic tool that sequences the entire genome and can pick up insertions or deletion of bases, structural variants and intronic single nucleotide variations.

Treatment groups

55 Participants
are divided into 2 treatment groups
Group A: Fetuses2 interventions
Group B: Neonates2 interventions

Trial outcomes

Primary outcomes

1

Identify known single gene disorders that would not be detected by microarray as a cause of nonimmune fetal hydrops by performing whole exome sequencing (WES)

Time frame
5 years
2

Identify novel genetic disorders associated with nonimmune hydrops

Time frame
5 years

Secondary outcomes

1

Evaluate the incremental value of whole genome sequencing (WGS) in the evaluation of fetal hydrops when WES is negative

Time frame
5 years
2

Better counsel the parents about the etiology of hydrops especially if they desire a subsequent pregnancy

Time frame
5 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Thomas Jefferson University

Lead sponsor

Source ClinicalTrials.gov
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