Loeys-Dietz Syndrome (LDS)

Loeys-Dietz syndrome (LDS) is a genetic condition that affects your connective tissue. Connective tissue typically provides strength and flexibility to many structures in your body. Loeys-Dietz syndrome mainly affects your:

• Heart and blood vessels
• Bones and joints
• Eyes
• Skin

You’re born with LDS, but you might not notice signs and symptoms until childhood or adulthood. LDS affects each person differently. The health impacts range in severity.

Loeys-Dietz syndrome gets its name from two doctors who first identified the syndrome in 2005. Before this discovery, healthcare providers misdiagnosed it as Marfan syndrome. This is another connective tissue disease that affects your body in similar ways.

Symptoms of Loeys-Dietz syndrome

Loeys-Dietz syndrome has four main features:

• Aneurysms. This is the widening of an artery. With LDS, it often affects your aorta, but you can have aneurysms in other arteries. You may not have symptoms of aneurysms, but imaging tests can detect them.
• Arterial tortuosity. This is when arteries are twisted or spiraled. It most often affects arteries in your neck. Imaging tests can detect them.
• Orbital hypertelorism. Widely spaced eyes are a distinctive craniofacial feature of LDS.
• Bifid or broad uvula. This means the little piece of flesh that hangs in the back of your mouth (uvula) is split or bigger than usual.

Most people with LDS have these four features. But the syndrome can affect several other parts of your body, causing other symptoms.

Physical features

Physical features of Loeys-Dietz syndrome may include:

• Cleft lip and palate
• Clubfoot or flat feet
• Craniosynostosis (early fusion of skull bones)
• Long fingers and toes
• Overly flexible joints (hypermobility)
• Pectus excavatum (sunken chest) or pectus carinatum (protruding chest)
• Scoliosis
• Skin that bruises and scars easily
• Skin that’s translucent (almost see-through) and velvety soft

Other features

Other features of LDS may include:

• Congenital heart disease, like patent ductus arteriosus (PDA), atrial or ventricular septal defect (ASD/VSD) and bicuspid aortic valve (BAV)
• Digestive system issues, like inflammatory bowel disease (IBD)
• Dural ectasia (ballooning or widening of the dural sac, which surrounds your spinal cord)
• Eye muscle disorders
• Hernias
• Food or environmental allergies

Loey-Dietz syndrome causes

Changes to certain genes cause Loeys-Dietz syndrome. These genes play roles in how your cells function during growth and development. They also manage the formation of structures in the spaces between cells (the extracellular matrix). This structure is important for tissue strength and repair.

An estimated 3 out of 4 people with Loeys-Dietz syndrome have no biological family history of the syndrome. For unknown reasons, a gene changes for the first time.

In about 1 out of 4 cases, you inherit LDS from a biological parent. LDS has an autosomal dominant pattern of inheritance. This means inheriting one copy of the faulty gene is enough to cause the syndrome. A parent with Loeys-Dietz syndrome has a 1 in 2 (50%) chance of passing the syndrome to each of their children.

Types of LDS

Different gene changes cause five distinct types of LDS. Symptoms can overlap between all five types. But each type tends to have distinct features (phenotypes). Types I and II are the most common.

Types of Loeys-Dietz syndromes and the gene changes that cause them include:

• LDS-I (TGFβR1). Type I mainly involves craniofacial (head and face) features.
• LDS-II (TGFβR2). Type II mainly involves skin (cutaneous) features.
• LDS-III (SMAD-3). Type III mainly involves aneurysms and osteoarthritis.
• LDS-IV (TGFβ2). Type IV mainly involves Marfan syndrome-like features, like aortic aneurysm issues.
• LDS-V (TGFβ3). Type V mainly involves aneurysms in your thoracic and/or abdominal aorta.

Complications of this condition

Cardiovascular complications are the most common — and serious — complications of Loeys-Dietz syndrome. Some examples include:

• Aortic dissection
• Left ventricular hypertrophy
• Mitral valve prolapse
• Subclavian artery dissection
• Stroke

Other LDS complications may include:

• Degenerative disk disease
• Hollow organ ruptures, like your intestine, spleen or uterus
• Osteoarthritis
• Osteoporosis and bone fractures
• Retinal detachment

How doctors diagnose this condition

Your healthcare provider will do a physical exam and ask about your medical history. If they think you may have Loeys-Dietz syndrome, they’ll refer you to a geneticist. This specialist will do genetic testing with a blood test to look for gene changes that cause the syndrome.

Your provider may recommend other tests to help diagnose cardiovascular conditions linked to LDS, like:

• Echocardiogram to check for aorta problems and heart defects
• Computed tomography angiogram (CTA) or magnetic resonance angiogram (MRA) from your head to your pelvis to check for aneurysms and twisting arteries

How is Loeys-Dietz syndrome treated?

There’s no cure for LDS. But various treatments and strategies can help manage your symptoms and prevent complications. You’ll need a treatment plan that’s specific to your health issues. This may include medications, frequent monitoring and/or surgery.

Medications and monitoring

Medications that can help slow down the enlargement of your aorta and other arteries include:

• Beta-blockers
• Angiotensin II receptor blockers (ARBs)

You might require open heart surgery to fix an aortic aneurysm or a defective heart valve. If you need heart valve surgery for LDS, you might need to be on an anticoagulant medication for the rest of your life. It depends on the type of prosthetic valve you receive.

You’ll need routine medical appointments to monitor your:

• Heart and blood vessels — in particular, the size of your aorta
• Eyes
• Skeletal system

This way, your healthcare team can track changes and catch any possible complications as soon as they appear. Your team will tell you how often you need these appointments. Monitoring for LDS usually involves imaging tests.

Physical activity guidance

Intense physical activity can strain your aorta and other connective tissues impacted by LDS. Because of this, you’ll work closely with a physical therapist to find exercises and sports that are safe for you.

Providers generally recommend low- to moderate-intensity exercise for most people with LDS. Activities that may be safer for your health include hiking, biking and swimming.

In general, you’ll likely need to avoid:

• Contact sports
• Exercise to exhaustion
• Isometric exercises, like planks and wall sits

Surgery

Healthcare providers often recommend certain heart surgeries for LDS to prevent complications, like aortic dissection. The most common surgery is aortic root replacement. Your healthcare team may recommend other cardiovascular surgeries depending on your symptoms.

You may need orthopedic surgery to help with scoliosis or foot deformities. Other therapies can help with musculoskeletal conditions, like braces.

What can I expect if I have this condition?

If you have Loeys-Dietz syndrome, you can expect a lot of medical appointments and the need to have a thorough understanding of your body. LDS affects everyone differently, so you’ll have your own journey with the syndrome. You’ll work closely with your team of healthcare providers to manage LDS as it changes.

LDS is still a relatively new disease. Experts are actively studying how it affects your health and life expectancy. So far, research shows that earlier detection and preventive treatments are helping people with LDS live longer.

Cardiovascular impairment is still the most common cause of death in LDS. This is mainly due to sudden death in undiagnosed cases. It’s also more likely to affect people who get a late LDS diagnosis.

LDS and mental health

Several aspects of living with Loeys-Dietz syndrome can impact your mental health and quality of life, like:

• The chronic nature of LDS and the need for lifelong treatment
• The ways LDS affects your appearance
• Chronic pain and fatigue
• Limits on physical activity, which are often social interactions
• Family planning stressors

Because of this, you may be at higher risk of:

• Anxiety
• Depression
• Experiencing bullying
• Social isolation

Caregivers and family members of people with LDS are also at risk of these mental health issues.

Be sure to seek help from a mental health specialist (like a psychologist) if you’re experiencing distress related to LDS. Your mental health is just as important as your physical health. Joining a support group may also help.

How does Loeys-Dietz syndrome affect pregnancy?

Pregnant women with Loeys-Dietz syndrome are at risk for uterine ruptures. Your uterus may suddenly tear during pregnancy or labor and delivery. This rupture can be life-threatening to you and your baby.

It’s important to receive care from a perinatologist (maternal-fetal medicine doctor). This expert specializes in high-risk pregnancies. Your provider may recommend delivering early or via Cesarean section (C-section).

What is the difference between Marfan syndrome and Loeys-Dietz syndrome?

Marfan syndrome (MFS) and LDS are both genetic conditions that affect your connective tissue. They typically share the feature of aortic aneurysms. But they have other differing features. For example, LDS often causes twisted or spiraled arteries, but MFS doesn’t.

They also result from different gene changes. For MFS, there’s a change in the gene that gives your cells instructions to make fibrillin. It’s the main component of elastic fibers in your connective tissue.

What is the difference between Ehlers-Danlos and Loeys-Dietz syndrome?

Ehlers-Danlos syndrome (EDS) and LDS are both genetic conditions that affect your connective tissue. But LDS mainly affects your heart and arteries, and EDS mainly affects your skin and joints.