Loeys-Dietz syndrome (LDS) is a genetic disorder that affects the connective tissue in the body. The disorder was first observed and described by Dr. Bart Loeys and Dr. Hal Dietz at the Johns Hopkins University School of Medicine in 2005.
Characterized by significant manifestations, such as aortic aneurysms, arterial tortuosity, craniofacial and skeletal anomalies, LDS results from pathogenic variants in key genes of the transforming growth factor-beta signaling (TGFβ) pathway.
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Main Characteristics
Loeys-Dietz syndrome (LDS) can affect many parts of the body, including the arteries, heart, bones and joints, skin, eyes, and other organ systems. LDS can look very different from one person to another. A person may have many of the characteristics described below or only a few. Importantly, someone can have significant aortic or arterial disease even when outward physical features of LDS are subtle.
Some of the most recognizable features associated with LDS include aortic and arterial aneurysms, arterial tortuosity, widely spaced eyes (hypertelorism), and a broad or split (bifid) uvula. These findings can provide important clues to a diagnosis, but not everyone with LDS has these features, and they are not required to be present for someone to have LDS.
Because LDS affects connective tissue throughout the body, its characteristics are best understood by body system.
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Cardiovascular and arterial involvement is one of the most important features of LDS.
Characteristics may include:
Aortic aneurysm, particularly enlargement of the aortic root
Aneurysms in other arteries throughout the body
Arterial tortuosity, meaning arteries that follow a twisting or winding course, particularly in the head and neck
Aortic or arterial dissection, in which a tear develops within the wall of an artery
Bicuspid aortic valve
Mitral valve prolapse or other valve abnormalities
Congenital heart defects, including atrial septal defect (ASD), ventricular septal defect (VSD), and patent ductus arteriosus (PDA)
Because LDS can affect arteries beyond the aortic root, vascular disease is not limited to the heart or aorta. The location, severity, and progression of arterial disease can vary considerably among individuals.
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Head and Face
Craniofacial features are among the historically recognized characteristics of LDS, although they can be subtle or absent.
Features may include:
Hypertelorism, or widely spaced eyes
Craniosynostosis, or early fusion of one or more of the skull bones
Malar hypoplasia, or relatively flat cheekbones
Downward slant of the eyes
Micrognathia or retrognathia, meaning a small or receding lower jaw
Blue or gray-appearing sclerae (the whites of the eyes)
The presence and prominence of these features vary among individuals and genetic subtypes.
Mouth and Teeth
Differences involving the palate, uvula, and teeth can occur in LDS.
These may include:
Broad or bifid (split) uvula
Cleft palate
High or narrow palate
Dental and enamel abnormalities
Crowding or other dental alignment concerns
A broad or bifid uvula is a well-recognized feature of LDS, but its absence does not rule out the condition.
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Loeys-Dietz syndrome can affect the bones, joints, and spine. These features vary widely from person to person and may include both increased joint flexibility and joint stiffness or contractures.
Characteristics may include:
Scoliosis or kyphosis (curvature of the spine)
Chest wall differences, including pectus excavatum (sunken chest) or pectus carinatum (protruding chest)
Joint hypermobility or instability
Joint or finger contractures, which limit movement
Long fingers and toes (arachnodactyly)
Clubfoot or other foot differences, including flat feet
Cervical spine abnormalities or instability
Early-onset osteoarthritis, particularly in some genetic subtypes
Low bone mineral density and increased risk of fractures in some individuals
The type and severity of skeletal and musculoskeletal features can differ considerably among people with LDS and among genetic subtypes. Some features may be present from birth, while others may become more apparent with growth or over time.
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Skin and other soft tissues may show signs of connective-tissue differences.
Features may include:
Thin or translucent skin
Visible veins
Soft or velvety skin
Easy bruising
Widened or abnormal scars
Stretch marks (striae)
Hernias
The degree of skin involvement varies and may be very subtle in some people.
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A variety of eye findings have been reported in LDS.
These may include:
Myopia (nearsightedness)
Strabismus (eye misalignment) or other ocular motility differences
Blue or gray-appearing sclerae
Retinal abnormalities, including retinal detachment in some individuals
Eye findings vary among individuals and genetic subtypes.
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Allergic and inflammatory conditions are increasingly recognized as part of the LDS spectrum, particularly in some genetic subtypes.
These may include:
Food allergies
Environmental allergies
Asthma
Eczema or other atopic conditions
Eosinophilic gastrointestinal disorders
Not everyone with LDS develops allergic or inflammatory disease, and these manifestations appear to be more strongly associated with some genetic forms of LDS than others.
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Gastrointestinal symptoms and conditions can occur in people with LDS.
These may include:
Gastroesophageal reflux
Feeding difficulties
Abdominal pain or other persistent gastrointestinal symptoms
Eosinophilic gastrointestinal disease, including eosinophilic esophagitis
Inflammatory bowel disease in some individuals
Gastrointestinal symptoms have many possible causes, so evaluation should be individualized.
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LDS can affect the respiratory system in several ways. Some respiratory problems are related to allergic disease, while others may reflect differences in connective tissue or the chest and spine.
Reported findings include:
Asthma
Pneumothorax (collapsed lung)
Emphysematous changes in some individuals
Abnormalities or weakness of the trachea or bronchi
Breathing difficulties associated with significant scoliosis or chest-wall differences
These findings are not present in everyone with LDS.
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Hearing and ear-related differences have been reported in people with LDS.
These may include:
Hearing loss
Recurrent or persistent ear problems
Ear, nose, and throat concerns associated with craniofacial or palate differences
Hearing concerns should be evaluated based on an individual's symptoms and clinical history.
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Some neurologic symptoms and findings can occur in LDS. In addition, the arteries supplying the brain and neck can be affected by the vascular features of the condition.
These may include:
Headaches or migraines
Tortuosity of arteries in the head and neck
Aneurysms or other abnormalities of cerebral and cervical arteries
Cervical spine abnormalities
Dural abnormalities
Neurologic symptoms are common in the general population and are not necessarily caused by LDS. New, severe, or unusual neurologic symptoms should be medically evaluated.
A Variable Condition
One of the most important things to understand about Loeys-Dietz syndrome is that there is no single LDS appearance or set of characteristics.
LDS is caused by genetic changes affecting the TGF-β signaling pathway. The genes associated with LDS include TGFBR1, TGFBR2, SMAD2, SMAD3, TGFB2, and TGFB3, as well as biallelic variants in IPO8, which cause a recessively inherited form within the LDS spectrum.
There is considerable overlap among the different genetic forms of LDS, but research has also identified differences in how frequently certain features occur and in the severity of some manifestations. Even people with the same genetic cause can have very different medical characteristics.
For this reason, the absence of characteristic facial, skeletal, skin, or other outward features does not exclude LDS or indicate that cardiovascular risk is absent.
An individual's care should be based on their specific genetic diagnosis, personal and family medical history, cardiovascular findings, and other manifestations.
What Does This Mean for Me?
The characteristics listed here represent features that have been observed in people with Loeys-Dietz syndrome. No individual with LDS should be expected to have all of them.
If you have LDS or are being evaluated for LDS, talk with a genetics professional and healthcare providers familiar with heritable connective-tissue and aortic conditions. They can help determine which findings and health considerations are relevant to you.
For more information about recommended evaluation, imaging, treatment, and ongoing care, see our Clinical Diagnosis and Treatment and Management resources.
Have a diagnosis and wondering what to do next? Check out our “Now What?” guide.
Diagnosis
Diagnosing Loeys-Dietz syndrome (LDS) involves looking at the whole person. Healthcare providers consider a combination of medical and family history, physical characteristics, cardiovascular and arterial findings, and genetic information.
Because LDS can vary widely from person to person—and some individuals have few outward signs—evaluation by healthcare professionals familiar with heritable connective tissue and aortic conditions is important.
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There is no single test or set of physical features that identifies every person with Loeys-Dietz syndrome (LDS), and there are currently no consensus clinical diagnostic criteria for LDS.
A clinical diagnosis may be made based on characteristic findings. Genetic testing can establish a molecular diagnosis, identify the genetic cause of LDS, and provide important information for medical care and family members.
Evaluation for LDS typically considers the whole picture, including a person's medical and family history, physical features, cardiovascular and arterial findings, and genetic testing when appropriate. Because LDS can vary considerably from person to person and among genetic subtypes, evaluation by healthcare professionals familiar with heritable connective tissue and aortic conditions is important.
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Evaluation for LDS typically includes a detailed medical and family history. Healthcare providers may look for a personal or family history of aortic or other arterial aneurysms, arterial dissections, arterial tortuosity, cardiovascular surgery, or sudden or unexplained death at a young age.
A history of other features associated with LDS—including skeletal, craniofacial, skin, allergic or inflammatory, gastrointestinal, and eye findings—may also provide important clues.
A family history of LDS or aortic disease can increase suspicion for the condition, but the absence of a family history does not rule out LDS. Some individuals are the first person in their family to have LDS because the genetic change occurred for the first time in them.
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A physical examination may identify features that support a diagnosis of LDS or suggest another heritable connective tissue disorder.
Healthcare providers may look for characteristics involving the:
Head, face, palate, and uvula
Bones, joints, chest, feet, and spine
Skin and connective tissue
Eyes
Other body systems based on the person's medical history and symptoms
No single physical characteristic is present in everyone with LDS. Some people have recognizable craniofacial, skeletal, or skin features, while others have few outward signs despite having significant cardiovascular or arterial disease.
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Cardiovascular evaluation is an important part of assessing someone for suspected LDS.
An echocardiogram uses ultrasound to evaluate the heart, heart valves, aortic root, and portions of the ascending aorta. It can identify aortic enlargement as well as valve abnormalities and certain structural heart differences associated with LDS.
Aortic measurements are interpreted according to factors such as age and body size.
Because an echocardiogram does not visualize the entire aorta or arterial system, additional vascular imaging may be needed to fully evaluate someone in whom LDS is suspected.
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LDS can affect arteries throughout the body, so evaluation may include imaging beyond the portion of the aorta that can be seen by echocardiography.
Magnetic resonance angiography (MRA) or computed tomography angiography (CTA) can be used to examine the aorta and other arteries from the head through the pelvis.
This imaging can identify:
Aortic and other arterial aneurysms
Aortic or arterial dissections
Arterial tortuosity, in which arteries follow a twisting or winding course
Other arterial abnormalities
Arterial tortuosity is a characteristic feature of LDS and is often particularly noticeable in the arteries of the head and neck.
The type and extent of vascular imaging needed should be determined by the individual's healthcare team.
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Genetic testing is an important part of the evaluation when LDS is suspected, but a negative genetic test does not necessarily exclude a clinical diagnosis of LDS.
A molecular diagnosis can identify the genetic cause of LDS and may help:
Confirm the diagnosis
Identify the genetic subtype
Inform medical management and surveillance
Clarify the inheritance pattern
Identify family members who may benefit from targeted genetic testing and medical evaluation
LDS is associated with pathogenic or likely pathogenic variants in TGFBR1, TGFBR2, SMAD2, SMAD3, TGFB2, and TGFB3, as well as biallelic pathogenic or likely pathogenic variants in IPO8, which are associated with a recessively inherited form of LDS.
Because LDS can overlap with other heritable aortic and connective tissue conditions, genetic testing is often performed using a multigene panel that includes genes associated with thoracic aortic aneurysm and dissection. In some circumstances, broader genetic testing may be appropriate.
If clinical suspicion for LDS remains high despite negative initial genetic testing, additional or updated testing may be considered as genetic testing technologies and knowledge of aortopathy genes continue to evolve.
Genetic test results should always be interpreted in the context of the person's clinical findings and family history. A variant of uncertain significance (VUS) does not by itself confirm or rule out a diagnosis of LDS.
A genetics professional can help individuals and families understand genetic test results and what they may mean for medical care and other family members.
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LDS shares characteristics with several other heritable connective tissue and aortic conditions, and distinguishing among these conditions is not always straightforward.
A person's combination of physical features, cardiovascular and arterial findings, family history, and genetic testing results can help healthcare providers determine the most appropriate diagnosis.
In some cases, a definitive diagnosis may not be possible immediately. Continued medical evaluation and reconsideration of genetic testing as knowledge and testing technologies evolve may provide additional answers over time.
Learn more about conditions that can resemble LDS in Differential Diagnosis.
Differential Diagnosis
Although Loeys-Dietz syndrome shows overlap with other disorders such as Marfan Syndrome (MFS), Ehlers-Danlos Syndrome (EDS), Shprintzen-Goldberg syndrome (SGS) and others, a variety of differential features set LDS apart from other disorders.
LDS and MARFAN SYNDROME
Individuals diagnosed with Marfan syndrome (MFS) exhibit several findings not found in LDS patients. These include:
ectopia lentis (dislocation of the lens of the eye)
dolichostenomelia (prominently long limbs)
Individuals with LDS tend to have a more translucent quality to their skin, allowing veins to be easily visible. Abnormal scarring and easy bruising also may occur to a greater degree in individuals with LDS.
Birth defects such as clubfoot, other structural heart defects and cleft palate (opening and obvious gap in the roof of the mouth) are also more likely to be associated with LDS.
It has also been discovered that the genetic cause for these two disorders is distinct. MFS is caused by a mutation (gene change) in the fibrillin-1 (FBN1) gene, while LDS is caused by a mutation the TGFBR1, TGFBR2, SMAD3, TGFB2, TGFB3 or SMAD2 gene.
LDS AND EHLERS-DANLOS SYNDROME
LDS is similar to vascular type Ehlers-Danlos (EDS) in that skin-related findings such as easy bruising, soft/velvety skin texture, wide scarring and translucent skin are seen in both syndromes. Both LDS and vascular type EDS have a relatively high instance of arterial aneurysms and, to a lesser degree, spontaneous organ rupture. Clubfoot may be observed in both disorders.
The disorders are different in that individuals with LDS have physical findings typically not present in individuals with vascular type EDS, such as widely-spaced eyes and bifid uvula.
Vascular type EDS occurs when the collagen an individual produces is not the appropriate quantity or quality. Genetic testing for a mutation in the COL3a1 gene or collagen biochemical studies performed on a skin biopsy sample can confirm this diagnosis. Individuals exhibiting EDS-like symptoms but who have had a normal test for vascular type EDS should be evaluated for LDS.
LDS AND SHPRINTZEN-GOLDBERG SYNDROME
Individuals with Shprintzen-Goldberg syndrome (SGS) and LDS may have similar findings, including craniosynostosis, pectus anomalies and scoliosis.
However, the vast majority of individuals with SGS do not show progressive or severe aneurysm formation of the aortic root or of other arteries. Another difference between these two disorders is that individuals with SGS are also more likely to show developmental delay. SGS is caused by mutations in the SKI gene.
Genetics and Inheritance
Loeys-Dietz syndrome is a genetic disorder that is caused by a mutation (gene change) in either the TGFBR1 or TGFBR2 genes (transforming growth factor beta receptor 1 or 2), the SMAD3 gene (mothers against decapentaplegic homolog 3), the TGFB2 gene (tgfbeta 2 or transforming growth factor beta 2 ligand) or the TGFB3 gene (tgfbeta 3 or transforming growth factor beta 3 ligand).
These genes encode for the receptors and other molecules involved in the tgf-beta pathway. Correlation between the genetic cause of LDS and physical manifestation continues to evolve (see gene association fact sheet).
There are SIX genetic causes of Loeys-Dietz syndrome, with the proposed naming system.
Loeys-Dietz syndrome 1 caused by mutations in the TGFBR1 gene
Loeys-Dietz syndrome 2 caused by mutations in the TGFBR2 gene
Loeys-Dietz syndrome 3 caused by mutations in the SMAD3 gene
Loeys-Dietz syndrome 4 caused by mutations in the TGFB2 gene
Loeys-Dietz syndrome 5 caused by mutations in the TGFB3 gene
Loeys-Dietz syndrome 6 caused by mutations in the SMAD2 gene
Although there is significant overlap between the clinical features caused by mutations in the different genes, we are learning about what might be differing features between the types and how this may impact medical management.
The term genetic disorder also indicates that the disorder has been present in an individual since conception. Loeys-Dietz syndrome exhibits an autosomal dominant inheritance pattern. This means that each offspring of an individual with LDS has a 50% chance of inheriting the gene mutation for LDS. There is no way to predict the severity of vascular, skeletal or skin findings that may occur in an offspring.
Many individuals are the first in their family to have the mutation causing LDS. These cases are caused by sporadic (random) mutations that occur during conception. There is no parental cause (medication or alcohol use for example) for the random mutation occurring. It is no one's fault.
For anyone who has the diagnosis of LDS and who is of reproductive age, it is recommended that they review the recurrence risk information with a genetics professional. There are testing options performed during pregnancy (prenatal diagnosis) and through in-vitro techniques (pre-implantation genetic diagnosis) to determine the presence of LDS in the fetus.
Have You Already Recieved a Genetic Test?
Understanding your genetic test results for conditions like Marfan, Loeys-Dietz, or VEDS can be challenging. Here’s a simple Q&A to help make sense of what your results may mean and what you might consider doing next.
Treatment & Management
There is no single treatment plan for Loeys-Dietz syndrome (LDS). Because LDS can affect many systems of the body—and because the type and severity of manifestations can vary considerably from person to person—care should be individualized.
The goals of LDS management are to identify and monitor cardiovascular and other complications, reduce the risk of aortic and arterial events, treat symptoms and other health concerns, and support long-term health and quality of life.
Management may involve specialists in cardiology, vascular and cardiovascular surgery, medical genetics, orthopedics, allergy and immunology, gastroenterology, pulmonology, ophthalmology, otolaryngology, rehabilitation medicine, maternal-fetal medicine, mental health, and other areas depending on an individual's needs.
An individual's care plan may be influenced by their genetic subtype, age, medical and family history, cardiovascular findings, rate of aortic growth, previous surgeries or vascular events, other LDS manifestations, and personal goals and preferences.
The latest LDS management recommendations emphasize multidisciplinary care and shared decision-making. People with LDS should work with healthcare professionals experienced in heritable aortic and connective tissue conditions whenever possible.
Cardiovascular & Arterial Surveillance
Regular cardiovascular and arterial imaging is a cornerstone of care for people with Loeys-Dietz syndrome (LDS). Because LDS can cause aneurysms, dissections, and arterial tortuosity throughout the body, surveillance includes both the aortic root and heart as well as the arterial system beyond the heart.
The type and frequency of imaging should be individualized. Factors such as a person's genetic subtype, age, family history, aortic and arterial measurements, rate of vessel growth, previous vascular events or surgery, and other cardiovascular findings may influence how often imaging is recommended.
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An echocardiogram (echo) uses ultrasound to evaluate the heart and nearby portions of the aorta. It is commonly used to monitor:
The size and growth of the aortic root and ascending aorta
Heart valve structure and function
Overall heart structure and function
For most people with LDS, echocardiography is recommended at least annually. More frequent imaging may be recommended when the aorta is enlarging, measurements are approaching a size of concern, or other cardiovascular findings require closer monitoring.
In children, aortic measurements are typically adjusted for body size and expressed as a z-score, which compares the measurement with what is expected for a child of similar body size.
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An echocardiogram cannot visualize the entire aorta or other arteries that may be affected by LDS. For this reason, periodic imaging of the arterial system from the head through the pelvis is an important part of LDS surveillance.
This is generally performed using:
Magnetic resonance angiography (MRA), which uses a magnetic field and does not expose the individual to ionizing radiation; or
Computed tomography angiography (CTA), which uses X-rays and provides highly detailed images of the blood vessels.
These studies can identify aortic and arterial aneurysms, dissections, arterial tortuosity, and other vascular abnormalities throughout the body.
When there are no findings requiring closer follow-up, head-to-pelvis arterial imaging is generally recommended at least every two years. More frequent or targeted imaging may be necessary depending on the individual's vascular findings and risk factors.
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Both MRA and CTA have important roles in LDS care, and the most appropriate imaging method depends on the clinical situation.
MRA is often useful for long-term surveillance because it avoids exposure to ionizing radiation and can provide imaging of large portions of the arterial system.
CTA provides excellent detail and can be particularly useful in emergency situations, for surgical planning, for evaluating smaller arteries and branch vessels, and for imaging after certain vascular procedures.
In young children, MRA may require sedation or general anesthesia because the individual must remain still for a longer period. CTA is much faster and can often be performed without sedation, but it involves radiation exposure.
The healthcare team should consider these benefits and limitations when selecting the appropriate imaging method for each individual.
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If imaging identifies an aneurysm, dissection, significant arterial enlargement, or another vascular abnormality, surveillance is typically more frequent and focused on the affected area.
The timing of follow-up imaging depends on factors such as:
The artery involved
Vessel size
Rate of growth or change
Genetic subtype
Personal and family history of aneurysm or dissection
Previous vascular surgery or intervention
Other features that may influence vascular risk
Whenever possible, comparison with previous imaging is important for determining whether a vessel is stable or changing over time.
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There is no single imaging schedule that is appropriate for every person with LDS. Recommendations may change over time as a person grows, cardiovascular findings change, new vascular abnormalities are identified, or additional information becomes available about the individual's genetic subtype.
People with LDS should work with a cardiologist and other cardiovascular specialists familiar with heritable thoracic aortic disease to develop an imaging plan appropriate for their individual circumstances.
Medications
Medications are commonly used in Loeys-Dietz syndrome (LDS) to reduce stress on the aorta and other arteries and to help slow the progression of aortic enlargement. Medication does not eliminate the risk of aneurysm or dissection and does not replace regular cardiovascular and arterial imaging.
The two primary classes of medications used for cardiovascular protection in LDS are angiotensin receptor blockers (ARBs) and beta-blockers. The choice of medication, dose, and whether more than one medication is used should be individualized based on a person's cardiovascular findings, blood pressure, heart rate, age, other medical conditions, and tolerance of treatment.
There is no single medication regimen that is appropriate for every person with LDS. Treatment decisions should take into account the individual's genetic subtype, cardiovascular findings, aortic growth, blood pressure and heart rate, other medical conditions, pregnancy considerations, medication tolerance, and previous vascular procedures or events.
Medication should be prescribed and adjusted in partnership with a healthcare professional familiar with LDS or other heritable aortic conditions. Individuals should not start, stop, or change cardiovascular medications without discussing the change with their healthcare team.
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Angiotensin receptor blockers (ARBs) are blood-pressure medications that are commonly used in people with LDS. Examples include losartan, irbesartan, and candesartan.
In experimental models of LDS, ARBs have been shown to reduce abnormal aortic growth. Although direct clinical trial data in people with LDS remain limited, experience from related heritable aortic conditions and our understanding of LDS biology support their use as part of medical management.
When tolerated, ARB therapy may be started early and the dose gradually adjusted to achieve an appropriate therapeutic effect while monitoring blood pressure and other factors.
ARBs should not be used during pregnancy because they can harm a developing fetus. Individuals who are pregnant or considering pregnancy should discuss medication planning with their cardiovascular and pregnancy care teams.
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Beta-blockers reduce the force and rate of the heartbeat and can decrease the mechanical stress placed on the aorta and arterial walls. Examples include atenolol, metoprolol, and propranolol.
Beta-blockers may be used alone or in combination with an ARB, depending on the individual's cardiovascular status and treatment goals.
Because beta-blockers can affect other body systems, the choice of medication should take an individual's overall health into account. For example, nonselective beta-blockers can worsen asthma symptoms in some people, which is particularly relevant because asthma and allergic disease occur more frequently in LDS.
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Some people with LDS may be treated with both an ARB and a beta-blocker.
Current LDS management recommendations support considering combination therapy when there is progressive aortic enlargement despite treatment with one medication, provided the medications are tolerated.
Medication doses should be individualized rather than based on a single blood-pressure or heart-rate target for everyone with LDS.
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Surgery repairs a specific area of the aorta or arterial system but does not eliminate the underlying connective tissue condition or the possibility of vascular disease elsewhere.
For this reason, cardiovascular medications are generally continued after aortic or vascular surgery when medically appropriate, along with ongoing imaging surveillance.
A Note About Other Medications
Some medications may require special consideration or may be avoided when appropriate alternatives are available for people with Loeys-Dietz syndrome. This does not mean these medications should not be used, but conversation and shared decision-making should be considered for their use.
See a table of medications that require careful consideration in the 2026 Updated Care Management Primer.
Aortic & Vascular Surgery
Surgery can play an important role in preventing life-threatening aortic and arterial complications in people with Loeys-Dietz syndrome (LDS). When an aneurysm reaches a size or shows other characteristics associated with increased risk, planned preventive surgery is generally safer than waiting for an aortic or arterial dissection or rupture to occur.
The timing and type of surgery should be individualized. Decisions may take into account the genetic subtype, size and location of the aneurysm, rate of growth, body size, age, family history, previous vascular events or surgery, heart valve function, other features associated with vascular risk, and pregnancy plans.
Whenever possible, people with LDS who require aortic or vascular surgery should be evaluated and treated at a center experienced in heritable aortic disease and complex aortic surgery.
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The aortic root, the portion of the aorta closest to the heart, is the most common location of an aneurysm at the time LDS is diagnosed.
Preventive aortic root surgery may be recommended before an aneurysm reaches the size at which surgery would typically be considered for someone without a heritable aortic condition. This is because aortic dissection can occur at smaller aortic dimensions in LDS.
The 2026 LDS management recommendations generally advise considering aortic root replacement at approximately 4.0–4.5 cm for individuals with TGFBR1-, TGFBR2-, or SMAD3-related LDS. Lower thresholds may be appropriate when additional risk factors are present.
There is less surgical experience for TGFB2-, TGFB3-, and SMAD2-related LDS, which generally have less aggressive aortic disease at the population level. In these genetic subtypes, intervention at an aortic root diameter of approximately 4.5 cm or greater may be reasonable, depending on individual risk factors.
These measurements are not automatic surgical cutoffs. Surgery may be considered earlier or later based on the individual's overall risk.
Factors That May Influence the Timing of Surgery
Aortic diameter is only one part of the decision about preventive surgery. Healthcare teams may also consider:
Rapid aortic growth
Family history of aortic dissection or rupture, particularly at smaller aortic dimensions
Previous aortic or arterial dissection
The individual's genetic subtype and, when known, information about the specific genetic variant
Significant aortic valve regurgitation
Aneurysms or other vascular disease elsewhere in the arterial system
Age and body size
Plans for pregnancy
Other clinical features associated with more aggressive vascular disease
The 2026 recommendations identify aortic growth greater than 0.5 cm per year as an additional indication that may influence consideration of aortic root surgery.
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Personalized External Aortic Root Support (PEARS) is a surgical approach that uses a custom-made external mesh support to reinforce the aortic root and ascending aorta while preserving the person's native aorta and aortic valve.
The 2026 LDS management recommendations recognize PEARS as a potential option for preventive aortic root surgery in selected adults with LDS. Experience in LDS is growing, but long-term LDS-specific outcome data remain limited, and the procedure is currently available only at select centers.
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When aortic root replacement is needed, a valve-sparing aortic root replacement is generally the preferred surgical approach when the person's own aortic valve is suitable for preservation.
In this operation, the enlarged portion of the aortic root is replaced with a synthetic graft while the person's natural aortic valve is preserved and reimplanted within the graft. This approach is sometimes called a David procedure.
Preserving the natural valve can avoid some of the long-term considerations associated with an artificial heart valve. However, valve-sparing surgery is not appropriate in every situation. If the valve cannot be preserved or repaired successfully, replacement of both the aortic root and valve may be necessary.
A bicuspid aortic valve does not automatically prevent a person with LDS from having valve-sparing surgery, although valve anatomy and function influence the decision.
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LDS can cause aneurysms and dissections throughout the arterial system, so some individuals may eventually require surgery involving the ascending aorta, aortic arch, descending or abdominal aorta, or other arteries.
Decisions about these procedures depend on the location and size of the affected artery, how quickly it is changing, symptoms, previous dissections or procedures, and the individual's overall vascular risk.
For aneurysms in arteries outside the aortic root, the relationship between the artery's size and its expected normal diameter can also help guide treatment. The 2026 recommendations suggest considering vascular intervention when there is rapid enlargement or when an artery reaches approximately two to three times its expected diameter, while recognizing that decisions must be individualized.
Surgery Does Not End Vascular Surveillance
Aortic or vascular surgery repairs a specific portion of the arterial system, but it does not eliminate the underlying connective tissue condition.
People with LDS require lifelong cardiovascular and arterial surveillance after surgery because aneurysms, dissections, or other vascular changes can develop in portions of the aorta or arterial system that were not repaired.
Follow-up imaging is individualized according to the type of surgery, remaining vascular findings, genetic subtype, and the person's medical history.
An Evolving Area of LDS Care
New surgical technologies and techniques will continue to change the options available to people with LDS. Because experience with some newer approaches remains limited, decisions should consider both what is known about short-term outcomes and what is still uncertain about long-term durability in genetically altered aortic and arterial tissue.
Participation in shared decision-making with an experienced aortic team can help individuals understand how established and emerging approaches apply to their particular anatomy, genetic subtype, medical history, and treatment goals.
Physical Activity, Musculoskeletal & Bone Health
Loeys-Dietz syndrome can affect the bones, joints, muscles, and spine. Depending on a person's needs, care may involve orthopedics, physical or occupational therapy, rehabilitation medicine, or other specialists.
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Scoliosis, chest wall differences, joint hypermobility or instability, contractures, foot differences, and cervical spine abnormalities may require monitoring or treatment.
Treatment depends on the specific concern and may include physical therapy, braces or orthotics, casting, and, when necessary, surgery.
Because cervical spine instability can occur in LDS, additional evaluation may be needed when symptoms are present or before certain procedures involving the neck.
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Some people with LDS have low bone mineral density or an increased risk of fractures. Good nutrition, adequate calcium and vitamin D, and appropriate weight-bearing activity can help support bone health.
Bone-density testing (via a Dexascan) may be considered for people with fractures, unexplained back pain, or other risk factors. Additional evaluation or treatment may be recommended when low bone density or bone fragility is identified.
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Physical and occupational therapy can help improve strength, joint stability, posture, balance, mobility, and everyday function.
Therapy should be tailored to the individual and take cardiovascular and exercise recommendations into account. The goal is to help people with LDS remain safely active and as independent as possible.
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Regular physical activity is an important part of staying healthy with Loeys-Dietz syndrome. Appropriate exercise can help improve cardiovascular fitness, muscle strength, joint stability, energy, mental health, and overall quality of life.
Exercise recommendations should be individualized based on a person's cardiovascular and arterial findings, musculoskeletal needs, and overall health. Activities involving heavy lifting, intense straining, or sustained isometric effort can cause significant increases in blood pressure and may need to be limited.
The Marfan Foundation's Exercise & Physical Activity Resource provides more detailed guidance for children and adults with Loeys-Dietz syndrome and related genetic aortic conditions, including information to help individuals and healthcare providers make informed decisions about physical activity.
Allergy, Gastrointestinal & Pulmonary Care
Allergic, gastrointestinal, and respiratory conditions can occur with LDS. Evaluation and treatment should be based on each person's symptoms and needs.
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Asthma, eczema, environmental allergies, and food allergies are more common in some forms of LDS. Persistent or significant symptoms may benefit from evaluation by an allergist or immunologist.
People with food allergies should have an appropriate allergy action plan. Epinephrine should be used for anaphylaxis when indicated.
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Gastrointestinal concerns may include reflux, constipation, abdominal pain, feeding or swallowing difficulties, and eosinophilic or inflammatory gastrointestinal disease.
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Respiratory concerns may include asthma, pneumothorax, and less common structural lung or airway abnormalities. Pulmonary evaluation may be appropriate when respiratory symptoms or structural concerns are present.
Pectus excavatum and scoliosis commonly occur in LDS. Their associated lung function impairments remain understudied in skeletal reviews, although both conditions can cause restrictive lung disease when severe.
Pain, Fatigue & Hypermobility
Pain, fatigue, and joint hypermobility can affect daily life for some people with LDS. Management should focus on maintaining comfort, function, strength, and participation in everyday activities.
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Musculoskeletal pain may be related to joint instability, muscle strain, spinal or orthopedic differences, or osteoarthritis. Persistent or worsening pain should be evaluated to identify possible causes rather than assumed to be an unavoidable part of LDS.
Treatment may include physical or occupational therapy, activity modification, and other individualized approaches to pain management.
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Fatigue can have many causes and should be evaluated when it is persistent or interferes with daily life. Contributors may include pain, sleep problems, medications, physical deconditioning, or other medical conditions.
Management should focus on identifying contributing factors while supporting appropriate physical activity, conditioning, sleep, and overall well-being.
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oint hypermobility can contribute to instability, pain, subluxations, and difficulty with everyday activities.
Physical and occupational therapy can help improve strength, joint stability, proprioception, and function. Bracing, splinting, or other supports may also be helpful for some individuals. Therapy should be individualized and coordinated with LDS cardiovascular and exercise recommendations.
Eyes, Hearing & Craniofacial Care
LDS can affect the eyes, hearing, teeth, palate, and development of the head and face. Appropriate evaluation and treatment can help address vision, hearing, dental, and functional concerns.
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A baseline comprehensive eye examination, including a dilated retinal exam, is recommended for people with LDS. Follow-up should be based on individual findings and symptoms.
Changes in vision should be evaluated promptly. People with LDS should also be familiar with the warning signs of retinal detachment, including new flashes of light, a sudden increase in floaters, or loss of part of the visual field.
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Hearing loss and recurrent ear problems can occur in LDS, particularly in people with palate differences.
Baseline hearing testing is recommended for adults. Children should have hearing evaluated beyond routine newborn screening, with additional testing during childhood and whenever hearing concerns or frequent ear infections occur.
An ENT or hearing specialist may be needed for persistent ear problems or hearing loss.
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Cleft palate, a small or receding lower jaw (mandibular retrognathia), and other differences in facial or jaw development may require evaluation by a craniofacial or orthodontic specialist. A bifid uvula may also indicate a submucous cleft palate, which should be evaluated when appropriate.
Cleft palate is generally treated using standard approaches with a multidisciplinary craniofacial team. Early orthodontic or facial orthopedic treatment may be helpful for some people with jaw or facial growth differences.
Regular dental care is also important because enamel defects, dental alignment problems, and other dental differences can occur in LDS.
Mental Health & Emotional Well-Being
Living with Loeys-Dietz syndrome can bring uncertainty, ongoing medical appointments, imaging, surgeries, and concerns about future health. These experiences can affect emotional well-being and may contribute to anxiety, depression, or medical post-traumatic stress.
Mental health is an important part of overall LDS care. Individuals and families should feel comfortable discussing changes in mood, anxiety, stress, sleep, or coping with their healthcare team.
Counseling, therapy, support groups, and medication when appropriate can all be helpful. Connecting with others in the LDS community may also provide valuable support and understanding.
Emergency Situations
Most health concerns associated with Loeys-Dietz syndrome are managed through regular monitoring and medical care. However, certain complications can develop suddenly and require urgent medical attention.
Because LDS affects connective tissue throughout the body it is helpful for individuals with LDS, their families, and healthcare providers to be familiar with potential emergency situations.
These complications do not occur in everyone with LDS, and the level of risk varies from person to person and among genetic subtypes. Knowing that these emergency situations can occur helps individuals, families, and healthcare professionals recognize why appropriate surveillance and emergency preparedness are important.
Check out our Emergency Preparedness Kit and Emergency Alert Card to have on hand as a first source of information for First Responders.
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AORTIC or ARTERIAL DISSECTION is a potentially life threatening complication related to aortic aneurysm.
Symptoms of aortic dissection include sudden severe chest pain, migrating to the chest, neck, back, abdomen and/or an extremity. Some individuals with aortic dissection have reported nausea, vomiting, shortness of breath, and collapse.
Symptoms of aortic dissection warrant activation of the EMS (call 911), and transport to the nearest hospital for aortic IMAGING (CTA, MRA, echocardiography) to confirm or exclude dissection, for stabilization, and appropriate treatment.
Stroke symptoms may present with neck artery dissections.
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SPONTANEOUS PNEUMOTHORAX, sometimes called a collapsed lung, occurs when air enters the space between the lung and chest wall and causes part or all of the lung to collapse.
Symptoms of spontaneous pneumothorax include chest, neck or back pain exacerbated by deep breathing, or difficult breathing due to pain.
HEMOPTYSIS, or coughing up blood from the respiratory tract, has been reported in people with Loeys-Dietz syndrome. In some cases, the underlying cause may not be immediately apparent.
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A retinal detachment occurs when the retina, the light-sensitive tissue at the back of the eye, separates from the tissues that support it. Retinal detachment has been reported in people with Loeys-Dietz syndrome and requires prompt evaluation to help protect vision.
Retinal detachment is typically painless. A person may notice a sudden increase in floaters (spots, specks, strings, or cobweb-like shapes in the vision), flashes of light, or a shadow, curtain, or veil moving across part of the visual field. Peripheral vision may decrease, and vision can become blurred or reduced as the detachment progresses.
Sudden new flashes or floaters, loss of part of the visual field, or the appearance of a curtain or shadow over the vision should receive urgent ophthalmologic evaluation.
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Rarely, rupture or perforation of internal organs has been reported in people with Loeys-Dietz syndrome. This may be related to increased fragility of connective tissues that provide strength and support to the walls of internal organs.
Symptoms depend on the organ involved. Rupture or perforation involving the gastrointestinal tract may cause sudden or severe abdominal pain, abdominal tenderness or swelling, nausea or vomiting, fever, or a significant change in bowel symptoms. If internal bleeding occurs, a person may also experience weakness, dizziness, fainting, rapid heart rate, or feeling unusually pale or unwell.
Because these symptoms can have many different causes, they do not necessarily indicate an organ rupture. However, sudden or severe unexplained abdominal or pelvic symptoms in a person with LDS warrant prompt medical evaluation, particularly when accompanied by signs of internal bleeding or severe illness.
Hollow-organ rupture is considered an uncommon complication of LDS and should not be expected to occur in most people with the condition.
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Pregnancy and the postpartum period require special consideration in LDS because cardiovascular and connective tissues are exposed to additional physiologic stress.
Potential serious complications include aortic or arterial dissection and other vascular complications. Uterine rupture has also been reported, although it is uncommon.
Pregnancy-related risks vary considerably depending on an individual's genetic subtype, cardiovascular history, aortic dimensions, previous vascular surgery, and other medical factors. Pregnancy in LDS should therefore be managed with appropriate multidisciplinary care.
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