Loeys-Dietz syndrome is a genetic disorder that affects the connective tissue. The connective tissue is important for providing strength and flexibility to the bones, ligaments, muscles, and blood vessels.
Loeys-Dietz syndrome was first described in 2005. Its features are similar to Marfan’s syndrome and Ehlers-Danlos syndrome, but Loeys-Dietz syndrome is caused by different genetic mutations. Disorders of the connective tissue can affect the entire body, including the skeletal system, skin, heart, eyes, and immune system.
People with Loeys-Dietz syndrome have unique facial features, like widely spaced eyes, an opening in the roof in the mouth (cleft palate), and eyes that don’t point in the same direction (strabismus) — but no two people with the disorder are alike.
There are five types of Loeys-Dietz syndrome, labeled I through V. The type depends on which genetic mutation is responsible for causing the disorder:
- Type I is caused by transforming growth factor beta receptor 1 (TGFBR1) gene mutations
- Type II is caused by transforming growth factor beta receptor 2 (TGFBR2) gene mutations
- Type III is caused by mothers against decapentaplegic homolog 3 (SMAD3) gene mutations
- Type IV is caused by transforming growth factor beta 2 ligand (TGFB2) gene mutations
- Type V is caused by transforming growth factor beta 3 ligand (TGFB3) gene mutations
Since Loeys-Dietz is still a relatively newly characterized disorder, scientists are still learning about the differences in the clinical features between the five types.
As a disorder of the connective tissue, Loeys-Dietz syndrome can affect nearly every part of the body. The following are the most common areas of concern for people with this disorder:
- blood vessels, especially the aorta
- skeletal system, including the skull and the spine
- immune system
- digestive system
- hollow organs, such as the spleen, uterus, and intestines
Loeys-Dietz syndrome varies from person to person. So not every individual with Loeys-Dietz syndrome will have symptoms in all of these parts of the body.
Due to the many life-threatening complications related to a person’s heart, skeletal, and immune system, people with Loeys-Dietz syndrome are at a higher risk of having a shorter lifespan. However, advances in medical care are constantly being made to help reduce complications for those impacted by the disorder.
As the syndrome has only been recently recognized, it’s difficult to estimate the true life expectancy for someone with Loeys-Dietz syndrome. Oftentimes, only the most severe cases of a new syndrome will come to medical attention. These cases don’t reflect current success in treatment. Nowadays, it’s possible for people living with Loeys-Dietz to lead a long, full life.
The symptoms of Loeys-Dietz syndrome can arise anytime during childhood through adulthood. The severity varies greatly from person to person.
The following are the most characteristic symptoms of Loeys-Dietz syndrome. However, it’s important to note that these symptoms aren’t observed in all people and don’t always lead to an accurate diagnosis of the disorder:
Heart and blood vessel problems
- enlargement of the aorta (the blood vessel that delivers blood from the heart to the rest of the body)
- an aneurysm, a bulge in the blood vessel wall
- aortic dissection, sudden tearing of the layers in the aorta wall
- arterial tortuosity, twisting or spiraled arteries
- other congenital heart defects
Distinct facial features
- hypertelorism, widely space eyes
- bifid (split) or broad uvula (the little piece of flesh that hangs down in the back of the mouth)
- flat cheek bones
- slight downward slant to the eyes
- craniosynostosis, early fusion of the skull bones
- cleft palate, a hole in the roof of the mouth
- blue sclerae, a blue tinge to the whites of the eyes
- micrognathia, a small chin
- retrognathia, receding chin
Skeletal system symptoms
- long fingers and toes
- contractures of the fingers
- scoliosis, curvature of the spine
- cervical-spine instability
- joint laxity
- pectus excavatum (a sunken chest) or pectus carinatum (a protruding chest)
- osteoarthritis, joint inflammation
- pes planus, flat feet
- translucent skin
- soft or velvety skin
- easy bruising
- easy bleeding
- abnormal scarring
- myopia, nearsightedness
- eye muscle disorders
- strabismus, eyes that don’t point in the same direction
- retinal detachment
Loeys-Dietz syndrome is a genetic disorder caused by a genetic mutation (error) in one of five genes. These five genes are responsible for making receptors and other molecules in the transforming growth factor-beta (TGF-beta) pathway. This pathway is important in the proper growth and development of the body’s connective tissue. These genes are:
The disorder has an autosomal dominant pattern of inheritance. This means that only one copy of the mutated gene is enough to cause the disorder. If you have Loeys-Dietz syndrome, there’s a 50 percent chance that your child will also have the disorder. However, about 75 percent of cases of Loeys-Dietz syndrome occur in people with no family history of the disorder. Instead, the genetic defect occurs spontaneously in the womb.
For women with Loeys-Dietz syndrome, it’s recommended to review your risks with a genetic counselor prior to getting pregnant. There are testing options performed during pregnancy to determine if the fetus will have the disorder.
A woman with Loeys-Dietz syndrome will also have a higher risk of aortic dissection and uterine rupture during pregnancy and right after childbirth. This is because pregnancy puts increased stress on the heart and blood vessels.
Women with aortic disease or heart defects should discuss risks with a doctor or obstetrician before considering pregnancy. Your pregnancy will be considered “high risk” and will likely require special monitoring. Some of the medications used in the treatment of Loeys-Dietz syndrome also shouldn’t be used during pregnancy due to a risk of birth defects and fetal loss.
In the past, many people with Loeys-Dietz syndrome were mistakenly diagnosed with Marfan’s syndrome. It’s now known that Loeys-Dietz syndrome stems from different genetic mutations and needs to be managed differently. It’s important to meet with a doctor who is familiar with the disorder in order to determine a treatment plan.
There’s no cure for the disorder, so treatment is aimed at preventing and treating symptoms. Due to the high risk of rupture, someone with this condition should be followed closely to monitor the formation of aneurysms and other complications. Monitoring may include:
- annual or biannual echocardiograms
- annual computed tomography angiography (CTA) or magnetic resonance angiography (MRA)
- cervical spine X-rays
Depending on your symptoms, other treatments and preventive measures may include:
- medications to lessen the strain on the body’s major arteries by reducing heart rate and blood pressure, such as angiotensin receptor blockers or beta-blockers
- vascular surgery such as aortic root replacement and arterial repairs for aneurysms
- exercise restrictions, such as avoiding competitive sports, contact sports, exercising to exhaustion, and exercises that strain the muscles, like pushups, pullups, and situps
- light cardiovascular activities like hiking, biking, jogging, and swimming
- orthopedic surgery or bracing for scoliosis, foot deformities, or contractures
- allergy medications and consulting with an allergist
- physical therapy to treat cervical spine instability
- consulting with a nutritionist for gastrointestinal issues
No two people with Loeys-Dietz syndrome will have the same characteristics. If you or your doctor suspects you have Loeys-Dietz syndrome, it’s recommended that you meet with a geneticist who is familiar with connective tissue disorders. Because the syndrome was just recognized in 2005, many doctors may not be aware of it. If a gene mutation is found, it’s suggested to also test family members for the same mutation.
As scientists learn more about the illness, it’s expected that earlier diagnoses will be able to improve medical outcomes and lead to newer treatment options.