Detecting prenatal anomalies early in pregnancy can help expectant families make informed decisions. Prenatal imaging and genetic testing can uncover a range of genetic disorders, congenital abnormalities and other issues.
In reproductive health, an important goal is to help families have the children they want, says Deborah Krakow, MD, professor and chair of UCLA Obstetrics and Gynecology. With early knowledge, families can explore options including surrogacy, donors and in vitro fertilization.
Traditional genetic testing methods such as karyotyping can detect large abnormalities (i.e., the extra chromosome 21 in Down syndrome). But those techniques cannot identify single-gene mutations, leaving thousands of conditions potentially undiagnosed.
Another challenge is disruptive care for families facing genetic disorders. Pregnant women do not typically deliver at children’s hospitals. Newborns with medical issues are frequently transferred out, and the separation can create stress and logistical problems for the family.
“If we can identify issues early, we can provide on-site care and have both mother and baby in a continuum of care here. That is better for families overall,” says Sulagna C. Saitta, MD, PhD, a pediatric geneticist at Ronald Reagan UCLA Medical Center and director of reproductive genetics.
Personalized, family-centered care is central to UCLA Health’s Reproductive Genetics Program. Drs. Krakow and Saitta are among its members, along with medical geneticists, pathologists, radiologists and maternal-fetal medicine specialists.
The team also collaborates with cardiology, neonatology and other disciplines. The program combines advanced prenatal imaging with in-house genomic testing to diagnose prenatal anomalies. That integrated approach is not widely available elsewhere.
“There’s two ways that this can work,” Dr. Saitta explains. “One, you’ve identified something, and now you can make a care plan for that baby and mom. The other is that maybe you found nothing via genetic testing, and that’s also valuable, because that also puts you in a pathway for clinical care.” For example, the care team can prepare the NICU and other support services at the time of delivery.
The program’s advanced diagnostics can also reveal actionable findings for the parents themselves, as Dr. Krakow describes.
“Some families didn’t realize that one of the parents had a heritable disorder, and we’ve been able to then provide them with advanced care to improve the quality of their lives,” she says.
For other families, it’s understanding why they had a previously affected child — and whether it could happen again.
Genome board review
In 2012, UCLA began offering exome sequencing to identify disease-causing variants. With more than 20,000 genes in the human genome, interpreting genetic data is a challenge. “You have to figure out what’s relevant and what’s not relevant,” explains Dr. Saitta.
To help make sense of the data, Drs. Saitta, Krakow and colleagues rely on an in-house genome board. The multidisciplinary group meets weekly to interpret findings from genetic testing and imaging tests such as high-level ultrasound and fetal MRI.
“We go beyond standard radiology,” Dr. Krakow says, which includes looking at the position of the ears and the size of the hands. “If there’s something that strikes us to fit a genetic disease, we can take that information to our genome board.”
The genome board can provide families with answers much faster than would be possible with commercial testing — in as little as two weeks.
According to Dr. Krakow, another key advantage is their ability to identify and discuss gene variants not previously associated with a disease — something commercial companies do not do.
“What we then do is try to model it and prove that we’ve landed on the correct gene or answer,” she says.
Pioneering research
Led by Dr. Krakow, the UCLA Reproductive Genetics Program uses mouse models to investigate the underlying biological mechanisms of the genetic disorders they uncover.
Dr. Krakow highlights the laboratory’s work on genetic mutations in the SIK3 (salt-inducible kinase 3) gene. Researchers used findings from mice altered for SIK3 and observed that the mice exhibited the same clinical features as the humans. This finding provided strong validation that the SIK3 mutation was the cause of the genetic disorder — even though SIK3 had not been linked to any human diseases before — and revealed to two families that they were at risk for children with a complicated genetic disorder.
Modeling rare genetic conditions is key to understanding the complex role of heredity and genetics in disease. Dr. Krakow’s team is also trying to develop targeted treatments to help ensure that patients are supported at every step of their reproductive journey.
For physicians seeking to provide the most advanced and compassionate care for their patients facing genetic disorders, Dr. Krakow says the UCLA Reproductive Genetics Program is available for consultation.
“It does take a village,” agrees Dr. Saitta.
