Fetal Genetic Testing

Genes carry the instructions that guide the body’s development and decide a person’s traits and features. Changes or “misspellings” in genes can lead to differences in physical and mental development; genetic testing looks for these changes, offering valuable insights into potential health conditions, even during the fetal stage, allowing for early intervention and care.

Genetic testing can inform your pregnancy and delivery decisions in several ways, including:

• Helping guide your care during pregnancy
• Providing insights into care options for your baby
• Assessing the risk of the same condition occurring in future pregnancies
• Connecting you with physicians who specialize in your baby’s condition
• Connecting you with other families facing similar diagnoses

The Fetal Precision Genetics Program offers a variety of prenatal genetic testing procedures, including chromosome studies done through amniocentesis, chorionic villous sampling (CVS), fetal blood sampling, or other prenatal samples, to help determine if concerns found in your prenatal ultrasound are related to an underlying genetic condition. Our specially trained doctors and genetic counselors review your results and help provide insight into your pregnancy or the health of the fetus.

Types of genetic testing include:

• Karyotyping
• Fluorescent in situ hybridization
• Chromosomal microarray analysis (CMA)
• Sequencing
• Cardiovascular genetic testing

What is karyotyping?

Changes in the number and structures of chromosomes can result in a genetic condition. A karyotype test allows doctors to examine both the number and shape of chromosomes in a cell sample, pinpointing specific genetic causes for a given condition.

Fetal karyotyping involves taking cells from CVS, amniocentesis, or blood (including cord blood). These cells are stained so that the chromosomes can be identified under a microscope. A “karyotype” is a picture taken of the 46 chromosomes from one cell, with all 23 pairs aligned from largest to smallest. A typical female karyotype is written as 46, XX, and a typical male karyotype as 46, XY, indicating the number of chromosomes and their gender type. Karyotyping is highly accurate in identifying significant changes in chromosomes, such as whole-chromosome loss or addition, or alterations in chromosome segments. However, it cannot detect small areas of duplication, deletion, or changes in a single gene. To have enough cells to examine for a karyotype, there is usually an incubation period, which means the results are available about two weeks after the sample is taken.

What is Fluorescent In Situ Hybridization?

Fluorescent In Situ Hybridization (FISH) helps doctors count specific pieces of DNA in a cell and can provide an initial result of the number of specific chromosomes (such as #21 for Down syndrome) in two days. Unlike traditional karyotyping, fetal cells in FISH don’t require a two-week culture or incubation period. Instead, a labeled DNA piece, known as a probe, attaches to similar DNA. For instance, when checking for Down syndrome during pregnancy, doctors use FISH on amniocentesis samples to count copies of chromosome #21. If there are three “signals” or bright spots on cells, it indicates three copies of chromosome #21, signaling Down syndrome. Although not as sensitive as karyotyping (detects extra DNA about 80 percent of the time), FISH is a preliminary test focused on common chromosome concerns (13, 18, 21, X, and Y). A modified FISH can also check for specific small missing or duplicated chromosome pieces.

What is chromosomal microarray analysis (CMA)?

CMA provides a more detailed view of chromosomes compared to even the most detailed karyotype. It detects not only whole and missing chromosomes but also additions or losses of chromosomes, which can’t be seen on even a detailed karyotype. CMA identifies changes in DNA known as copy number variants (CNVs), representing extra (trisomy) or missing (monosomy) segments of a chromosome. The size of the CNV and the affected genes are important considerations. CNVs may be benign, uncertain, or pathogenic (previously linked to specific conditions and outcomes). CMA is the recommended genetic analysis when concerns arise from ultrasound observations of fetal structure or in cases of stillbirth.

What is sequencing?

Sequencing offers a closer examination of DNA, and it can be done on the same sample used for karyotyping, FISH, or CMA. Whole Exome Sequencing (WES) focuses on the portion of DNA containing crucial instructions for organ development and cell function. Changes in this portion of DNA, called the exome, can be benign or pathogenic (leading to altered development or function). Some changes, known as Variants of Unknown Significance (VUS), are unclear until further research is conducted. Understanding changes identified by WES can be challenging, providing discussions on potential concerns when pathogenic changes are found. If a VUS is identified, additional study and research may determine its impact. WES contributes significantly to caring for ill infants and is increasingly considered when fetal conditions are suspected.

Whole Genomic Sequencing takes the investigation of the DNA a step further by examining much of the remaining DNA. It helps uncover alterations in the genes that regulate important genes, even if the vital genes themselves are intact.

What is cardiovascular genetic testing?

Cardiovascular genetic testing looks for and examines genetic factors related to heart conditions.

Doctors choose a genetic test based on their specific objectives and the information needed for diagnosis or treatment planning, including cardiovascular genetic testing. For instance, karyotyping provides a comprehensive assessment of the entire chromosome set, suitable for detecting large-scale abnormalities, despite a longer turnaround time. FISH offers results within two days and is specifically targeted for common chromosomal concerns, making it a good option when timely information is critical. CMA is often chosen for a detailed analysis of both large and small chromosomal abnormalities, while sequencing provides an in-depth examination of individual genes and specific mutations.