Congenital anomalies affect more than 6% of live births worldwide. In the United States, about one in every 33 babies is born with one of these conditions. They are a leading cause of infant mortality, childhood hospitalizations and lifelong disability. Yet despite their impact, congenital anomalies remain underrecognized and underfunded, and for many families, unexplained.

That gap between burden and understanding is the focus of a new white paper published in Developmental Biology as part of a special issue on congenital anomalies. The paper brings together five lead authors, more than 60 contributing scientists and clinicians, and endorsements from major scientific societies. Irene Zohn, PhD, principal investigator in the Center for Precision Medicine and Genomics Research at Children's National Hospital, is among the authors helping shape this field-wide call to action.

The message is simple. We have the tools to identify the causes of many more congenital anomalies, but progress depends on investing, collaborating more effectively and treating patients and families as research partners.

Why so many families still lack answers

Advances in genome sequencing have transformed the search for genetic causes of disease. For some families, sequencing has provided long-awaited answers. For many others, the search continues.

More than half of individuals with congenital anomalies still do not receive a definitive genetic explanation. Even when sequencing is performed, results often include variants of uncertain significance, genetic changes that cannot yet be clearly linked to disease. Families may spend years navigating tests and referrals without answers, often described as the "diagnostic odyssey". The white paper argues that this reflects system-level gaps rather than a lack of scientific potential.

Two priorities to move the field forward

The authors outline a framework centered on two key investments. First, they call for expanded and improved genomic analysis. This includes broader access to genome sequencing, better analytic tools and stronger data sharing across institutions. It also requires consistent terminology to accurately measure the true scope of congenital anomalies and recognize the magnitude of the problem.

Second, the paper emphasizes the need for mechanistic research. Identifying a genetic variant is only the first step. Researchers must also understand how that variant disrupts development and whether the consequences can be prevented or treated. This requires sustained support for functional studies using cell models, patient-derived tissues and animal systems. Together, these approaches can shorten the diagnostic journey, improve confidence in genetic findings, and accelerate the development of new therapies.

Putting patients and families at the center

A defining feature of the roadmap is its focus on patient partnership. Families should be treated as active participants in research, including through the return of results and clear communication about uncertainties. Genomic data should also be reanalyzed over time, since findings that are unclear today may become meaningful as science advances. Building systems that support this process is essential to improving care.

A pivotal moment for the field

Congenital anomalies are not rare when considered together. They represent a significant public health challenge with lifelong consequences for children and families. Science is advancing rapidly, but progress depends on aligning investment, infrastructure and collaboration with the scale of the problem. This white paper argues that the field is at a turning point. With focused support for genomic diagnosis, functional research and patient-centered partnerships, researchers and clinicians can deliver answers and improve outcomes for children who have waited too long.

You can read the full article, "Challenges and opportunities for understanding the genetic causes of congenital anomalies," in Developmental Biology here.