A New Era in Loeys-Dietz Syndrome Care Personalized Care for a Complex Condition
More than two decades after Loeys-Dietz syndrome (LDS) was first identified, an updated management primer is redefining how clinicians understand and care for the condition.
The recommendations in the original LDS primer, published in 2014, helped establish basic standards of care for what was still considered a newly recognized connective tissue condition. At the time, the guidance was highly focused on one thing: preventing catastrophic aortic events.
“It was time,” says genetic counselor Gretchen MacCarrick, MS, CGC, the paper’s lead author. “It has been 12 years and there have been new findings as well as questions on many things like musculoskeletal care, anesthesia, and women’s health. We focus so much on the aorta and the arteries, but there's a lot of other health concerns. This time, there is a much greater priority on quality of life in terms the day-to-day things that impact patients.”
You can read the full Primer, which is published in Genetics in Medicine, here.
The recommendations were first developed in Antwerp, Belgium, at the first European Loeys-Dietz Syndrome Patient and Research Networking conference. Supported and facilitated by the European Joint Programme on Rare Diseases, and the Marfan Foundation, the June 2023 meeting brought together international clinicians and researchers. “Ultimately, more than 40 authors from seven countries contributed to the document, representing nearly a dozen medical subspecialties,” she says.
Advances in genetic research—including insights into the TGF-β signaling pathway—have led researchers to recognize Loeys-Dietz syndrome as a connective tissue condition with a wide spectrum of features between LDS subtypes and between individuals. With this in mind, the new guidance leans heavily toward personalized care plans, shaped by:
genotype-informed risk assessment
tailored vascular surveillance
patient-specific timing of surgery
individualized medication strategies
personalized counseling for pregnancy and lifestyle
“We’re moving away from a one-size-fits-all kind of treatment,” says MacCarrick. “There is a focus on subtypes and what we call precision medicine. We look at how your specific LDS type and even your specific genetic variant, as well as your family and personal history, may impact your medical care.”
The shift toward precision medicine can be seen in how the new management recommendations approach the different LDS subtypes. While there can be overlaps, LDS types 1 and 2 are generally considered more vascularly severe and often require closer monitoring. "In the new guidelines we are still pretty clear on the timing of getting MRAs and CTAs and surgical thresholds," says MacCarrick. "But for types 3-6, which may have less vascular risk or present at later ages, there's more nuance in how frequently you need imaging. Maybe you can space it out a little bit more."
The guidelines are also heavily focused on the concept of shared decision-making between patients, families, and physicians. “This way you can have a plan that is appropriate for you as an individual or family,” she says.
The updated recommendations “reflect how far the field has come,’ says Bart Loeys, MD, who along with Hal Dietz, MD, first described the condition in 2005. “Our goal is that every person with LDS benefits from timely diagnosis, thoughtful surveillance, and individualized care that translates scientific progress into better outcomes and better lives.”
Beth Utz says that when her son Alex, now 26, was diagnosed with LDS two decades ago, “there was just a tiny blurb, a few sentences, on Dr. Dietz’s page on the Johns Hopkins website. It said LDS was more aggressive than Marfan syndrome. That was it. So now, 20 years later, I am so excited about all this new information.”
Beth knows her family was fortunate because they immediately established a working relationship with Dr. Dietz; one that continues today.
Still, Beth felt guilty because she had access to the world’s leading medical experts on LDS. “I wondered what other people were doing and how they were going to get information,” she says. “That’s why I wanted to start the Loeys-Dietz Foundation with Gretchen.”
Vigilant Cardiovascular Monitoring
Despite advances in diagnosis and treatment, aneurysms and dissections continue to pose a life-threatening risk for individuals living with LDS. The new primer continues to underscore the importance of regular surveillance.
However, the new recommendations also illustrate how much more sophisticated cardiovascular care has become. MacCarrick notes that the authors took into account new research regarding the PEARS procedure – a novel valve-sparing technique that does not replace the aorta and is currently only available in Europe.
While echocardiography remains the first-line imaging tool for monitoring the aortic root and ascending aorta, imaging now often extends well beyond the heart. It is suggested that many patients undergo imaging of the entire arterial tree — from the head to the pelvis —as aneurysms and arterial abnormalities can occur throughout the body.
Magnetic resonance angiography (MRA) is the preferred method for arterial imaging because it provides detailed images without exposing patients to radiation. In some cases, computed tomography angiography (CTA) may still be used, particularly in emergencies or for surgical planning.
For children, physicians use specialized measurements adjusted for body size and growth over time in order to identify dangerous changes as early as possible. Imaging decisions may also take into account factors such as radiation exposure and the need for anesthesia in young children.
Beyond the Aorta
Another important evolution is the recognition that cardiovascular care in LDS extends beyond monitoring the aorta.
Researchers and clinicians are increasingly paying attention to additional cardiac complications including:
mitral valve disease
arrhythmias
abnormalities involving the heart muscle itself
Cerebrovascular disease
The primer highlights growing awareness of potential heart rhythm abnormalities in some individuals with LDS. In certain situations, physicians may use additional tools such as electrocardiograms (ECGs) or Holter monitors to evaluate arrhythmia risk, particularly in patients with mitral valve abnormalities or concerning symptoms.
The document also reflects the increasing role of genotype-informed care. For example, mitral valve prolapse appears to occur more frequently in individuals with SMAD3-related LDS, helping physicians tailor surveillance more precisely to the individual patient.
"This new information is so important for all of us living with this condition,” says Alison Lemmer. “As a mother with Loeys-Dietz syndrome, who is raising a child with LDS, I know how crucial it is to receive proper, up-to-date medical guidance. But traditionally, patients have found themselves having to educate healthcare providers, many of whom have never even heard of this condition. Many of the rules and stipulations recommended to us are very outdated – or sometimes simply incorrect. I am thankful to the professionals who have done the research and put in the time to ensure that we have the proper medical care to live long happy, healthy lives."
A Broader View of Loeys-Dietz Syndrome
While the original primer recognized that LDS affects multiple body systems, the updated version significantly expands guidance in several areas. “When we first described LDS, we were mainly focused on a certain young cohort who were very clearly affected,” says MacCarrick. “Now that we see the whole spectrum of Loeys-Dietz syndrome, how it impacts non-vascular features, how it impacts people in older populations, how it potentially impacts women and hormonal issues-- we’ve really tried to answer some of those additional quality of life questions.
MacCarrick explains that the new primer is organized by almost every major organ system that somebody living with LDS should consider.
For example, the updated primer takes a deeper look at allergy, inflammatory, and gastrointestinal issues associated with LDS. For example, treating chronic or recurrent sinus infections may help improve asthma control. The connection highlights a broader theme throughout the document: health issues that seem unrelated can often be intertwined. The primer also recommends antihistamines for mild food reactions and reserving epinephrine for life-threatening reactions.
Orthopedic care, in particular, may now extend beyond scoliosis alone to include chronic pain, joint instability, and mobility challenges that significantly affect daily quality of life.
Pregnancy and reproductive care are another major area of expanded guidance. The updated primer emphasizes individualized counseling and planning long before conception, including a review of vascular imaging and discussion of potential risks. Throughout pregnancy, patients are encouraged to work with a multidisciplinary high-risk team. The recommendations also reflect a more personalized approach to delivery planning, with decisions based on factors such as aortic size and obstetric considerations rather than a one-size-fits-all approach.
For the first time, the primer also includes guidance on anesthesia—an area that has received little attention in previous recommendations. According to MacCarrick, the document outlines important considerations for both patients and anesthesiologists, including the possibility of difficult airway management, cervical spine instability, and joint hypermobility that may affect positioning during procedures. It also addresses issues such as managing blood pressure medications and monitoring heart rate and blood pressure before, during, and after anesthesia.
Another new finding is that some types of LDS may have an increased chance of hearing loss. The new primer recommends performing baseline audiological evaluations in adults. In the pediatric population, hearing should be assessed at age two and again at the start of kindergarten.
The update also expands discussion around, neurovascular disease, Pectus deformities, migraines, and more.
MacCarrick hopes that the new primer will help level the playing field for all people living with LDS. “The goal is that people who may not have access to a major Marfan Foundation Center, will now have access to the same information, regardless of where they live.”
MacCarrick hopes that people will bring this new resource when they visit their primary care physicians and specialists. “It should help providers take good care of patients,” she says. “But it should also help patients to develop good questions to ask their doctors and to become really great advocates for themselves and their kids.”
What the Updated LDS Primer Means for You
Register for the Global Virtual Conference, May 15–18, and don’t miss this timely session on Wednesday, June 17, from 12:00–12:50 pm.
Understanding the Updated LDS Primer for Diagnosis and Management, led by genetic counselor Gretchen MacCarrick, MS, CGC, and medical geneticist Julie Richer, MD, FRCPC, FCCMG, will walk participants through the most important updates in the new guidance.
Whether you’re newly diagnosed or have been living with LDS for years, you’ll gain practical insights to help you better understand your diagnosis, care, and treatment options.
This primer integrates extensive clinical experience and consensus expert opinion aimed at optimizing care for individuals with Loeys-Dietz syndrome. - Hal Dietz