Loeys-Dietz Syndrome

What Loeys-Dietz syndrome is

LDS was first described in 2005 by Bart Loeys and Harry Dietz. It is caused by variants in genes that control the transforming growth factor beta (TGF-beta) signaling pathway, which helps build and maintain the walls of blood vessels and other tissues. Faulty signaling weakens the arterial wall, so arteries enlarge, become tortuous (twisted) and can tear.

Unlike many aneurysm conditions, LDS affects arteries throughout the body: the aortic root, the whole aorta, and arteries of the head, neck, chest, abdomen and pelvis. Aneurysms can dissect (tear) at smaller diameters and younger ages than in Marfan syndrome, sometimes in childhood.

Types of Loeys-Dietz syndrome

Severity varies even within one family.

Symptoms and features

Blood vessels and heart

• aortic root aneurysm, found on echocardiogram
• aneurysms and twisting of arteries elsewhere, especially in the neck (vertebral and carotid arteries)
• aortic dissection or rupture
• heart defects such as patent ductus arteriosus, atrial septal defect or a bicuspid aortic valve
• mitral valve prolapse

Face and mouth

• widely spaced eyes (hypertelorism)
• a split (bifid) uvula, the dangling tissue at the back of the throat, or cleft palate
• early fusion of skull bones (craniosynostosis)
• blue-tinged whites of the eyes, squint
• a long face, small jaw or high-arched palate

Bones and joints

• scoliosis and neck spine instability
• clubfoot or flat feet
• chest wall deformity (pectus excavatum or carinatum)
• loose, hypermobile joints, or early osteoarthritis in SMAD3 cases
• long fingers and limbs in some people
• low bone density and fractures

Skin and other organs

• soft, velvety, translucent skin with visible veins
• easy bruising and wide scars
• hernias
• allergies, eczema, asthma and food allergy, including eosinophilic gut disease
• uterine rupture or arterial tears in pregnancy

Loeys-Dietz vs Marfan vs Ehlers-Danlos

Ehlers-Danlos syndrome and other connective tissue disorders can overlap, which is why genetic testing is important.

Diagnosis

1. Clinical assessment by a geneticist or cardiologist experienced in aortic disease.
2. Genetic testing, usually a multi-gene panel for aortic disease. A positive result confirms the type and allows testing of relatives.
3. Echocardiogram to measure the aortic root.
4. CT or MR angiography from head to pelvis at diagnosis, to map aneurysms and tortuosity in all arteries.
5. Spine X-rays of the neck for instability, and other imaging as needed.

First-degree relatives (parents, siblings, children) should be offered genetic testing and imaging.

Treatment

There is no cure, but treatment reduces the risk of dissection and rupture.

Medicines

• Beta-blockers or angiotensin receptor blockers such as losartan to lower blood pressure and stress on artery walls
• Strict blood pressure control

Monitoring

• Echocardiograms at least yearly, more often if the aorta is enlarging
• Head-to-pelvis MRA or CT at regular intervals, often every 1 to 2 years

Surgery

• Preventive aortic root replacement at smaller diameters than in Marfan syndrome, often around 4.0 to 4.5 cm in adults depending on the gene, family history and growth rate. Valve-sparing surgery is often possible.
• Repair of aneurysms in other arteries, often by open surgery, since endovascular stents can fail in fragile tissue.
• Cleft palate, craniosynostosis, clubfoot and scoliosis surgery as needed.

Lifestyle

• Avoid contact sports, heavy lifting, straining and maximal exertion; moderate aerobic activity is encouraged
• Avoid stimulants and decongestants that raise blood pressure
• Avoid fluoroquinolone antibiotics when possible, as they have been linked to aortic aneurysm and dissection
• Wear a medical alert ID
• Allergy and eczema management

Pregnancy

Pregnancy carries a high risk of aortic dissection and uterine rupture. Pre-pregnancy counseling and care in a high-risk obstetric and cardiology center are essential.

Outlook

Early reports, before the condition was widely recognized, described many deaths from dissection in young adulthood. Since then, earlier diagnosis, regular imaging, blood pressure medicines and preventive surgery have greatly improved survival, and many people now live long, active lives. Outcome depends on the gene involved, the severity of vascular disease and close follow-up.

Frequently asked questions

What are the signs of Loeys-Dietz syndrome?

Common signs include widely spaced eyes, a split uvula or cleft palate, aortic aneurysm, twisted arteries, scoliosis, clubfoot, chest wall deformity, flexible joints, soft translucent skin and easy bruising. Many people also have allergies or eczema. Features vary even within families.

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

Both cause aortic aneurysms, but in Loeys-Dietz they can tear at smaller sizes, affect arteries throughout the body and come with twisted arteries. Loeys-Dietz often causes widely spaced eyes and a split uvula, while Marfan causes lens dislocation. Different genes are involved.

What is the life expectancy with Loeys-Dietz syndrome?

Life expectancy has improved substantially since LDS was first described. With genetic diagnosis, regular imaging, blood pressure control and timely preventive surgery, many people live into older adulthood. Your specialist can discuss risk based on your gene and imaging.

Is Loeys-Dietz syndrome inherited?

Yes. It is autosomal dominant: each child of an affected person has a 50% chance of inheriting it. About 3 in 4 people have a new variant not present in either parent. Genetic counseling is recommended for families.

Can people with Loeys-Dietz syndrome exercise?

Yes, moderate aerobic exercise such as walking, cycling and swimming at a comfortable pace is encouraged. Contact sports, heavy weightlifting, isometric straining and competitive sports should be avoided. Your cardiologist can give personal limits based on your aortic measurements.