For many people living with an isolated lymphatic malformation (LM)/complex lymphatic anomaly (CLA) finding the right diagnosis and treatment can be a long and frustrating journey. Even patients with similar symptoms may respond differently to the same therapies, leaving families and clinicians searching for answers.
New research suggests those answers may lie in our genes.
In a recent presentation, Dr. Carrie Shawber, Associate Professor at Columbia University, shared how advances in genetics are transforming our understanding of isolated LMs and CLAs. From improving diagnosis to identifying potential new treatments, her work highlights how precision medicine could shape the future of care.
Why Genetics Matter
Lymphatic anomalies are a group of rare disorders caused by abnormal development or function of the lymphatic system. These conditions include isolated LMs, primary lymphedema, and CLAs such as generalized lymphatic anomaly.
Scientists now know that many of these disorders are linked to changes in DNA. Some genetic variants are inherited, while others develop after conception and affect only certain cells in the body. These differences help explain why two patients with similar diagnoses may have very different symptoms and treatment responses.
Expanding the Genetic Picture
Genetic testing has become an important tool for diagnosing lymphatic anomalies, but it is still evolving.
According to Dr. Shawber, researchers have expanded the number of genes associated with lymphatic anomalies from about 35 to more than 70. However, many current genetic testing panels do not include all of these genes, meaning some patients may never receive a complete genetic diagnosis.
Improving genetic testing could help clinicians diagnose patients earlier, better understand disease progression, and choose treatments based on the underlying biology rather than symptoms alone.
A Step Toward Personalized Treatment
Several targeted medications—including sirolimus, alpelisib, and trametinib—are already being used to treat some lymphatic anomalies. However, these therapies are not equally effective for every patient.
To better understand why, Dr. Shawber's laboratory tested more than 1,300 existing drugs using patient-derived cells and laboratory models. One class of medications, known as proteasome inhibitors, showed particularly promising results.
The drug bortezomib, already approved for certain cancers, reduced abnormal lymphatic vessel growth in preclinical studies. While these findings are encouraging, they have so far been observed only in laboratory and animal models. Clinical trials will be needed before this approach can be considered for routine patient care.
Looking to the Future
Perhaps the most ambitious part of Dr. Shawber's work is a new ARPA-H-supported research initiative designed to improve genetic discovery in lymphatic anomalies.
The project has already enrolled more than 1,700 participants and aims to build one of the world's largest genomic databases dedicated to these rare disorders. By combining genetic information with detailed clinical data, researchers hope to discover new disease-causing genes, improve diagnostic testing, and accelerate the development of personalized therapies.
Why This Research Matters
For patients and families, advances in genetics offer more than scientific discovery—they offer the possibility of clearer answers.
As researchers continue to identify new genes and develop more comprehensive genetic testing, physicians may be able to diagnose lymphatic anomalies earlier and select treatments based on each person's unique genetic profile.
While much of this work is still in the research stage, it represents meaningful progress toward a future where care is more precise, more personalized, and more effective for people living with lymphatic anomalies.
Every new discovery brings us one step closer to that goal.
From the video: Understanding the genetics of fetal and pediatric lymphatic anomalies
