Two siblings with same mutation reveal power of early cancer screening
The white glow in Daniel Oakes’ right pupil was not a trick of light. When the 2½-year-old moved his head, the shine remained — a bleached-out version of the red-eye effect seen in flash photography. That glow was retinoblastoma, a cancer of the eye that is fatal if left untreated. By the time doctors confirmed the diagnosis, Daniel’s entire right eye was nothing but tumor. His left eye, they discovered, was also riddled with disease. His mother, Brittany Oakes, watched her son endure months of chemotherapy, radiation, and surgery. Ultimately, surgeons removed both eyes and replaced them with prosthetics.
The family then learned something that would change their understanding of what had happened. Daniel had been born with a rare genetic mutation that gave him a roughly 90 percent risk of eye cancer. The mutation sat in a gene called RB1, discovered decades earlier as the first identified tumor suppressor gene. It was a finding that had reshaped cancer biology, yet for families like the Oakes, it offered no comfort. The knowledge came too late. The tumors had already grown, spread, and consumed what they would consume.
Three years later, Daniel’s sister Eveyana was born. She carried the same mutation. But her story unfolded differently from the very beginning. Genetic testing at six weeks of age gave doctors a head start they never had with Daniel. They monitored her eyes closely, zapping away tumors as soon as they began to sprout. Cancer never advanced. Eveyana never received chemotherapy. She never received radiation. She kept her vision. Lisa Diller, a pediatric oncologist at Dana-Farber Cancer Institute and Harvard Medical School in Boston who works with the family, points to the two siblings as a living demonstration of what early detection can achieve
The contrast between brother and sister illustrates the power of newborn screening for retinoblastoma. Yet such screening is not routinely offered for this or any cancer risk. Diller and a growing number of doctors are working to change that. For certain cancers, screening newborns could identify at-risk children before the first whispers of disease appear, preparing doctors to pounce on any emerging tumor. Once cancer has crept throughout the body, treatments tend to become more aggressive, with long-term side effects that can shadow a child for decades.
The push is part of a larger, global effort to expand newborn screening for genetic disorders more generally. Across the board, open questions remain about which conditions should be included. But screening for cancer poses special challenges. Some cancer-linked genes carry only a low risk of disease, says Richard Parad, a neonatologist at Mass General Brigham for Children and Harvard Medical School. Consider a baby girl with a gene variant that gives her a 15 percent risk of cancer. There is an 85 percent chance she will be fine. Is that gene worth testing for? “That’s a hard question to answer,” Parad says. Scientists are currently debating the merits of such tests and figuring out how to communicate risk to parents. For some cancers, including Daniel’s, the benefits of genetic testing are clear. For others, not so much.
Daniel himself is doing well now. He buzzes through school, competes in track meets, and plays video games like other 14-year-old boys. He relies on sound cues and controller vibrations to navigate games on his PlayStation. His parents have to remind him to use his cane at school. Blindness has not seemed to slow him down much, his mother says. Still, she sometimes wonders what life would have been like had genetic testing been available for Daniel. She thinks to herself, “Man, why couldn’t we have had this?”
The Blood Spot That Holds a Lifetime of Answers
Federal guidelines in the United States recommend that newborns be screened for 40 core conditions at birth. Those tests can also turn up 26 other conditions. The actual number each infant is screened for varies by state: 66 in Massachusetts, where Daniel was born, 75 in California and Connecticut, 35 in Vermont, and 36 in Kansas. A day or two after birth, nurses prick babies’ heels and collect a few drops of blood on a card. Those blood spots contain loads of chemical compounds that stack up into a ziggurat of health information and can reveal whether a child has a specific disease.
In many cases, the benefit of such screening is obvious. Take phenylketonuria, which doctors began testing newborns for in the 1960s. In babies with the disease, a certain protein building block amasses to toxic levels in the body. Left untreated, this can cause brain damage. Yet treatment is straightforward: a low-protein diet that limits the troublesome building blocks. There are all sorts of rare diseases like this with available treatments, says medical geneticist David Bick of Genomics England in London. Diagnosing babies at birth can change the course of their lives and even save them. “Newborn screening has been perhaps the most successful public health initiative in the world,” he says
Yet there is a lot of data that remains untapped, much of it in babies’ DNA. In deciding what screenings might be added, medical geneticist Sharon Plon points to three key considerations. The condition must be serious. There must be some sort of treatment available. And the test must be cost-effective, says Plon, of Baylor College of Medicine and Texas Children’s Hospital in Houston. Several cancers could fit the bill. In a project with Alex’s Lemonade Stand Foundation for Childhood Cancer, a national nonprofit based in Wynnewood, Pennsylvania, Plon, Diller, Parad, and their colleagues are developing a new test that would screen for cancer risk.
Presented in April at the annual American Association for Cancer Research meeting in San Diego, their approach includes a panel of nine genes implicated in childhood cancer. These cancers have clear patient monitoring recommendations in early childhood, Plon says. If a child tests positive, doctors have a plan — as in Eveyana’s case, where a mutation in her RB1 gene prompted regular eye exams and timely treatment of burgeoning tumors. The panel was designed not as a broad net but as a targeted tool. Each of the nine genes was chosen because mutations in them are known to predispose children to specific cancers that can be monitored and treated early. The goal is not to identify every possible risk but to catch the ones where early intervention makes a measurable difference.
The history of newborn screening stretches back more than half a century, and its evolution has been marked by both triumphs and cautionary tales. The first successful screening program targeted phenylketonuria in the 1960s, following the development of a simple bacterial inhibition assay by Robert Guthrie. That test allowed a drop of blood on filter paper to reveal whether a newborn carried the metabolic disorder. Within a decade, screening programs had spread across the United States and much of the developed world. The model proved so effective that it was gradually extended to other conditions: congenital hypothyroidism, sickle cell disease, cystic fibrosis, and dozens more. Each addition required new infrastructure, new laboratory techniques, and new protocols for communicating results to families. The current system, with its state-by-state variability, reflects that piecemeal growth.
The dried blood spots collected at birth have become a subject of intense scientific interest. They contain not just the chemical compounds used for traditional screening but also DNA that can be extracted and analyzed. This has opened the door to genomic newborn screening, an approach that goes far beyond the metabolic tests of the past. Instead of looking for a handful of specific chemical markers, genomic screening can examine genes associated with a wide range of conditions, from rare metabolic disorders to cancer predisposition syndromes. The technology has advanced rapidly, with the cost of whole-genome sequencing dropping from billions of dollars per genome in the early 2000s to under a thousand dollars today. But the ability to generate data has outpaced the ability to interpret it. Knowing that a child carries a gene variant is not the same as knowing what that variant means for their future health.
Nine Genes, One Thousand Lives, and the Questions That Remain
Diller and Parad tested a similar gene panel using archived dried blood spots from nearly 2,000 Michiganders born from 1987 to 2020 and known to have malignant childhood tumors. The panel identified nearly 7 percent of the kids who would develop cancer by age 8, the team reports in Nature Communications. That number might sound tiny, Parad says. But it would translate to roughly 1,000 babies born in the United States every year who would develop cancer as children. “We could find them before they have a problem,” he says. And that could help doctors detect and treat the cancers early, so the kids could avoid the toxic treatments that often come with a later diagnosis.
The study drew on a remarkable resource: dried blood spots that had been stored for decades, some for more than 30 years. Every baby born in Michigan since the mid-1980s has had a blood spot collected at birth, and those spots have been retained in a state repository. The researchers were able to link those spots to cancer registries, identifying which children went on to develop malignant tumors. This retrospective approach allowed them to test their panel against known outcomes, measuring how many cancer cases the genes would have flagged at birth. The 7 percent figure represents the sensitivity of the panel within this specific group, a group already known to have developed cancer. In the general population, the number of babies who would test positive but never develop cancer remains an open question.
Wendy Chung, a clinical and molecular geneticist at Boston Children’s Hospital, says she would love to see more data, like how many babies born with abnormalities in these genes do not go on to get disease. Unpublished data from Chung’s team suggests that cancer risk estimates associated with certain gene variants may be overestimated. One of the risks of newborn screening for cancer, Chung says, is that it could lead to anxiety about test results, as well as follow-up testing that may prove unnecessary. A positive result on a newborn screen is not a diagnosis of cancer. It is a warning flag, a signal that further monitoring may be warranted. But for parents, the distinction can be difficult to hold onto. The psychological weight of knowing a child carries a cancer-associated gene can be substantial, even when the actual risk is modest.
Similar questions are currently thrumming in Plon’s mind: “How much screening and stress are we going to put the families through?” And: “How well do we know these genes and their cancer risks?” These are not rhetorical questions. They are the central challenges facing the field as it moves toward broader implementation. The researchers are also grappling with how to present results to parents in a way that is honest about uncertainty without being needlessly alarming. Risk communication in genomics is a field in itself, drawing on psychology, behavioral economics, and clinical experience. A 15 percent risk of cancer means different things to different families. Some will want every possible monitoring option; others may prefer not to know. The design of the screening program, including how consent is obtained and how results are delivered, will shape the experience of thousands of families.
The American Cancer Society estimates that 9,680 children in the United States ages 0 to 14 will be diagnosed with cancer in 2026. That number serves as a backdrop for the entire debate. Every one of those children will have a family, a story, and a treatment journey. Some will face aggressive therapies with lasting side effects. A portion of those cancers, the researchers argue, could be caught earlier if newborns were screened for the right genetic markers. The 9,680 figure also puts the panel’s potential impact in perspective. If 7 percent of childhood cancers could be identified at birth, that would represent roughly 680 children each year whose families would have advance warning. Not all of those children would be spared the ordeal of treatment, but many would benefit from earlier detection and less toxic interventions.
In 2026, the researchers hope to launch a clinical trial in Boston and Houston. They plan to approach up to 10,000 parents of newborns about screening with either a nine-gene cancer panel or a more focused two-gene test. Both tests include RB1, the gene mutated in Daniel’s and Eveyana’s cancers, and WT1, or Wilms tumor 1, another well-described gene that carries childhood cancer risk. The larger panel also includes cancer genes that extend risk beyond the eye and kidney, covering a broader range of pediatric malignancies. The trial will measure not just whether the screening works technically, but whether it provides benefit to families and whether the psychological costs are acceptable. It will also generate the kind of data that Chung and others have called for: how many babies with these mutations actually develop cancer, and how many never do.
The trial’s design reflects the lessons learned from decades of newborn screening. It is cautious, incremental, and designed to answer specific questions before expanding further. The two-gene arm will focus on the conditions where the evidence is strongest, where monitoring protocols are well-established, and where the benefits of early detection are most clearly documented. The nine-gene arm will cast a slightly wider net, testing whether additional genes can be added without causing undue anxiety or unnecessary medical interventions. The comparison between the two arms will help researchers understand what is gained by expanding the panel and what costs come with it. The results will inform not just this program but the broader national conversation about what newborn screening should include in the years ahead.
Sources
1. Dana-Farber Cancer Institute