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

Phase

N/A

Condition

Birth Defects

Holoprosencephaly

Treatment

Whole Exome Sequencing

Whole Genome Sequencing

Clinical Study ID

NCT03911531

IRB18D.728

Ages 16-55
All Genders

Study Summary

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

Inclusion

The following inclusion criteria will apply:

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
Negative workup for Parvovirus B19, cytomegalovirus, toxoplasmosis, and syphilis
Negative fetomaternal hemorrhage workup as a cause for hydrops For cases of neonatal hydrops, the criteria for invasive prenatal testing will not be required as a postnatal blood sample from the hydropic infant will be the source of proband DNA.

The following exclusion criteria will apply:

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
Donor egg or donor sperm were utilized for conception
Fetus/Infant diagnosed with lysosomal storage disease
Pregnant woman or father of the baby less than 16 years of age
Hydrops was diagnosed concomitantly with intrauterine fetal demise

Study Design

Whole Exome Sequencing

January 15, 2019

December 31, 2025

Study Description

This is a prospective cohort study design for fetuses or neonates affected with NIHF. Mother-father-fetus trios of pregnancies complicated by idiopathic non-immune fetal hydrops will be identified. These patients will be counseled by a Maternal-Fetal Medicine specialist as would be the routine. As part of the routine work-up, amniocentesis will be recommended for karyotype, CMA and an infectious work-up. Amniocentesis will be performed by the Maternal-Fetal Medicine specialist of the referring institution. The patient will also be offered genetic counseling (routine). Subjects will be offered enrollment when inclusion criteria are met. After enrollment, the following samples will be collected: (1) maternal blood (2) paternal blood, (3) fetal DNA isolated from amniocytes (4) neonatal blood when referral is done postnatally. The WES results will be reported to the genetic counselor dedicated to the study. The parents will be contacted by the genetic counselor and counseled on the findings whether they were positive or negative. The result will also be communicated to the patient's primary MFM provider or pediatrician and appropriate referrals to pediatric genetics specialists will be made by the primary provider. In cases where no genetic disorder is identified, the sample will be stored and then subsequently whole genome sequencing will be performed.

Connect with a study center

Thomas Jefferson University
Philadelphia, Pennsylvania 19107
United States
Active - Recruiting

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