A groundbreaking initiative in genetic screening is changing the landscape of early diagnosis for rare diseases, and KnowTheGlow (KTG) had the opportunity to learn more about its potential impact. In a recent meeting, KTG Co-Founder Megan Webber, Board Member Cindy Mays, and Director of Global Outreach Helene Dameris spoke with Dr. Wendy Chung, the principal investigator of the GUARDIAN study and Chief of the Department of Pediatrics at Boston Children’s Hospital, and genetic counselor Rachel Klein. Their discussion explored how advancements in genome sequencing could revolutionize newborn screening (NBS), including the early detection of retinoblastoma (RB) and other vision-threatening conditions.
The GUARDIAN (Genomic Uniform screening Against Rare Disease In All Newborns) study is one of the most comprehensive genome sequencing initiatives ever conducted for newborns. Unlike standard newborn screening, which typically tests for around fifty conditions in the U.S., the GUARDIAN study examines approximately 450 rare genetic diseases, giving families the chance to intervene early and improve medical outcomes. The study does not replace newborn screening but serves as an adjunct, aiming to fill gaps where current testing may fall short. The research is currently underway at six NewYork-Presbyterian hospitals in New York City, with plans to expand to multiple states. The initiative is a collaborative effort supported by the New York State Department of Health, Illumina, GeneDx, Illumina, Columbia University Irving Medical Center, NewYork-Presbyterian Hospital and Sanofi, all working toward the goal of gathering critical data that could help influence national newborn screening policies.
Parental consent is a crucial component of the study, beginning with outreach in the third trimester of pregnancy. Most parents are approached bedside immediately after birth, and 74% have consented to participate. Because the study uses the same blood sample collected for routine newborn screening, no additional blood draw is required. Results are typically available within three to six weeks, and if a baby tests positive for a condition, the family is immediately connected with specialists and care coordinators to ensure timely medical intervention.
The study prioritizes conditions that appear early in childhood. To be included in the screening panel, a disorder must have a median onset or need for treatment before age five and a high chance of developing the condition. All babies participating in the study are screened for conditions in Group 1 (321 conditions), which include conditions that have treatment that prevent or ameliorate the symptoms of the condition. Parents can also choose whether they want to have their baby tested for conditions in Group 2 (144 conditions), which includes conditions associated with epilepsy which can be treated although there may be remaining neurological issues. For some conditions, children may also benefit from early intervention services.
The study’s initial findings were recently published in the Journal of the American Medical Association (JAMA). Over an 11-month period, 4,000 newborns were enrolled and 3.7 percent of newborns had positive screenings. The majority of those positive screens would not have been picked up by traditional NBS today. Of the newborns with true positive findings, 92% had a confirmed diagnosis for a condition not included in traditional NBS, reinforcing the accuracy of the process and its potential to transform early diagnosis in newborns.
The inclusion of retinoblastoma (RB) in Group 1 of the study means that babies found to carry genetic markers for RB could benefit from early intervention. Other retinal dystrophies are also being screened for, offering an unprecedented opportunity to detect eye diseases at birth. Although no babies with RB have been identified yet, the data being collected could provide valuable insights into the incidence and genetics of RB and help improve awareness of its early warning signs.
The study’s early findings are already proving to be life-saving. Among the most common conditions detected so far, approximately 200 cases of G6PD deficiency, an enzyme deficiency affecting red blood cells, have been identified. Another major discovery has been the detection of approximately 10 cases of Long QT Syndrome, a heart condition linked to sudden infant death syndrome (SIDS). By identifying this condition at birth, doctors have been able to intervene before tragedy strikes. The study team hopes to screen 100,000 babies to generate the necessary evidence for the expansion of the traditional NBS and prevent the delays in diagnosis and treatment.
Beyond the scientific data, Dr. Wendy Chung stressed the importance of patient stories in shaping public awareness and policy changes. While statistics are critical, real-life narratives bring the urgency of early detection to life. Families who have directly benefited from newborn genetic screening have become some of the most powerful advocates for expanding these programs nationwide. Their stories illustrate what could have been avoided had screening been available sooner—making a compelling case for why initiatives like the GUARDIAN Study should become standard practice.
For KnowTheGlow, this conversation reinforced the crucial role that early diagnosis plays in preventing childhood blindness. The inclusion of RB in the GUARDIAN Study panel represents a significant step forward in the potential for genetic screening to detect RB at birth. If this research succeeds in influencing universal newborn screening policies, it could transform the early detection and treatment of RB and other childhood eye conditions worldwide.
KTG sees an opportunity to collaborate with the GUARDIAN Study in raising awareness about RB genetic screening and the power of early diagnosis. By leveraging patient stories and engaging in advocacy, KTG can help ensure that RB and other childhood eye diseases remain a priority in newborn screening discussions.
The GUARDIAN Study is not just about genetics—it is about saving lives and preventing suffering before it begins. The future of newborn screening is changing, and through partnerships, education, and advocacy, we can work together to ensure that every child has the best possible chance at a healthy future.
