Prenatal genetic evaluation of the anomalous fetus
- Neeta Vora, MD
Neeta Vora, MD
- Assistant Professor
- University of North Carolina School of Medicine
- Sarah Harris, MS, CGC
Sarah Harris, MS, CGC
- University of North Carolina School of Medicine
Approximately 3 percent of live births are affected by a major structural malformation . With advances in prenatal ultrasound, many of these anomalies are now identified before birth. The etiology is diverse and includes environmental factors, genetic factors, or a combination of both. (See "Birth defects: Approach to evaluation".)
As the landscape of genetic testing rapidly evolves, clinicians are often left with many questions about the most appropriate testing methods to use for their patients. We will present our recommendations for a reasonable approach for the genetic evaluation of an anomalous fetus.
FREQUENCY OF CHROMOSOME ABNORMALITIES IN ANOMALOUS FETUSES
The finding of a fetal structural anomaly increases the possibility of a chromosome abnormality or genetic molecular defect and should prompt further evaluation into genetic etiologies. The frequency of a chromosome abnormality depends on the specific anomaly, the number of anomalies, and the combination of anomalies identified . In several retrospective series of prenatally detected anomalies on ultrasound that prompted genetic studies, an isolated fetal anomaly was associated with fetal chromosomal abnormalities in 2 to 18 percent of cases; multiple anomalies were associated with a fetal chromosomal abnormality in 18.8 to 35 percent [2-6].
Our approach — We offer an invasive procedure for diagnostic testing to patients with structural fetal abnormalities on ultrasound examination (algorithm 1) . The goal is to determine whether there is a genetic etiology of the abnormalities and thus enable well-informed counseling about prognosis, reproductive options, obstetric and pediatric management, and recurrence risks.
The decision to undergo invasive testing is very personal and must be based on the individual patient's personal values and goals. Pretest counseling by a provider familiar with the suspected fetal diagnoses and with genetic testing options is necessary for patients to make informed decisions. Alternatives to invasive diagnostic testing include noninvasive screening and postnatal testing.
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- FREQUENCY OF CHROMOSOME ABNORMALITIES IN ANOMALOUS FETUSES
- DIAGNOSTIC TESTS
- Our approach
- Fluorescent in situ hybridization
- Karyotype and chromosomal microarray analysis
- Gene sequencing
- - Targeted gene sequencing
- - Whole exome sequencing
- SCREENING TESTS
- Our approach
- Cell-free DNA
- GENETIC EVALUATION OF THE FETUS WITH "SOFT MARKERS" AND NO STRUCTURAL ANOMALIES
- Soft markers detected before blood or serum aneuploidy screening
- Soft markers detected after a negative blood or serum aneuploidy screen
- Evaluation for other disorders
- Pretest counseling
- Post-test counseling
- SUMMARY AND RECOMMENDATIONS