How Genomics Is Changing the Way Clinicians Treat Vascular Birthmarks in Children

The treatment of vascular birthmarks has been transformed over the past 15 years by advances in genomics and the repurposing of targeted cancer therapies. Somatic mutations occurring during fetal development, rather than inherited, have been identified as drivers of conditions like venous and arteriovenous malformations, opening the door to pathway-specific treatment.

In April 2022, the US Food & Drug Administration (FDA) granted accelerated approval to alpelisib (Vijoice; Novartis) for adult and pediatric patients aged ≥ 2 years with severe manifestations of PIK3CA-related overgrowth spectrum who require systemic therapy.1 This is 1 example of how oncology-derived agents are now reaching this patient population. Other agents, including oral sirolimus and the MEK inhibitor trametinib, are also being used or studied in this space, often in multidisciplinary settings alongside hematology and oncology.

At Maui Derm NP+PA Summer 2026, Ilona Frieden, MD, professor of dermatology and pediatrics at the University of California, San Francisco, offered an update on where the science stands and what clinicians should know.2 In the following Q&A, the third in a series covering her session at the meeting, Frieden outlines which mutations are implicated, how and when to consider testing, and which therapies are being used or studied. Read the first two parts of the interview on expanding dupilumab use and pearls for using drugs for common conditions.3,4

HCPLive: Can you walk us through your session on vascular birthmarks and the role of genomics?

Frieden: In the last 15 years, we've been able to identify mutations in tissue that cause vascular birthmarks, just in a region of the body. These are called somatic mutations. It's not a germline mutation; it's not passed from parent to child, but these are mutations that occur during the course of development.

Everyone is a mosaic in some form or other, and that's what we mean by that. In this case, these mutations cause dilated veins, capillaries, arteries—things like that.

Understanding what the genes are that result in these conditions has allowed us to look for medications that can target them. I talk about testing and how one goes about testing for these mutations and when you should consider testing. Then I talk about some of the emerging medications that can be used for treatment.

HCPLive: Which treatments are currently being used or studied for these conditions?

Frieden: Sirolimus is available in an oral form and is one of the main ones we use because it does target 1 of the major pathways involved in the formation of these conditions. Oral sirolimus is not FDA approved for that use, but it's very widely used.

Then there are drugs like MEK inhibitors [and] drugs like alpelisib. Alpelisib is approved for treating breast cancer, but the PIK3 gene mutation that causes certain forms of breast cancer also causes these birthmarks in a developmental sense. Not because they're going to [develop] cancer, but because if you have a mutation in development, it can lead to a specific kind of birthmark. You can use drugs that inhibit PI3K, block these pathways, and improve people's lives considerably.

Alpelisib is now actually FDA approved for the treatment of certain vascular malformations, even down to 2 years of age. There are others emerging that are not yet FDA approved, including one called trametinib, which is a MEK inhibitor used for treating arteriovenous malformations and other vascular malformations.

HCPLive: How should clinicians approach prescribing these medications?

Frieden: The idea [here is] not that we do these on our own. I personally think that you always want to be partnering with a hematologist or oncologist when you are giving these kinds of medications.

These are examples that really need to be done in a multidisciplinary setting where you have additional expertise. [This session is] really to give people an update on what's on the horizon because more of these are in clinical trials and will be used in the near future.

References

1. Frieden I. Pediatric Dermatology Update 2026. Session presented at the Maui Derm Summer 2026 meeting in Colorado Springs on June 26.

2. Frieden I. Expanding Use of Dupilumab in Pediatric Patients, With Ilona Frieden, MD. HCPLive. Published on June 27, 2026. Accessed June 30, 2026. https://www.hcplive.com/view/expanding-use-dupilumab-pediatric-patients-ilona-frieden-md

3. Frieden I. Pearls for Using Drugs for Common Conditions, With Ilona Frieden, MD. HCPLive. Published on June 30, 2026. Accessed July 7, 2026. https://www.hcplive.com/view/pearls-drugs-common-conditions-ilona-frieden-md

4. Singh S, Bradford D, Li X, et al. FDA Approval Summary: Alpelisib for PIK3CA-Related Overgrowth Spectrum. Clin Cancer Res. 2024;30(1):23-28. doi:10.1158/1078-0432.CCR-23-1270