Loeys-Dietz syndrome is a genetic disorder of the body’s connective tissue. It has some features in common with Marfan syndrome, but it also has some important differences. People with Loeys-Dietz syndrome features need to see a doctor who knows about the condition to decide if they have the disorder; often this will be a medical geneticist. It is very important that people with Loeys-Dietz syndrome get an early and correct diagnosis so they can get the right treatment.
What causes Loeys-Dietz syndrome?
Loeys-Dietz syndrome is caused a genetic mutation in one of 5 genes that tell the body how to make protein important for connective tissue.
- Loeys-Dietz syndrome 1 (LDS1) is caused by mutations in the TGFβR1 gene (Transforming growth factor beta receptor, type1)
- Loeys-Dietz syndrome 2 (LDS2) is caused by mutations in the TGFβR2 gene (Transforming growth factor beta receptor, type 2)
- Loeys-Dietz syndrome 3 (LDS3) is caused by mutations in the SMAD3 gene (Mothers against decapentaplegic homolog 3)
- Loeys-Dietz syndrome 4 (LDS4) is caused by mutations in the TGFβ2 gene (Transforming growth factor beta 2)
- Loeys-Dietz syndrome 5 (LDS5) is caused by mutations in the TGFβ3 gene (Transforming growth factor beta 3)
When any of these genes has a mutation, growth and development of the body’s connective tissue and other body systems is disrupted, leading to the signs and symptoms of Loeys-Dietz syndrome.
What are the key features of Loeys-Dietz syndrome?
Because connective tissue is found throughout the body, Loeys-Dietz syndrome features can occur throughout the body, too, including the heart, blood vessels, bones, joints, skin, and internal organs such as the intestines, spleen, and uterus.
One of the key features of Loeys-Dietz syndrome is aortic aneurysm or dissection. In Loeys-Dietz syndrome, aneurysms and dissections also can occur in arteries other than the aorta.
Other features of Loeys-Dietz syndrome include:
- Arteries that twist and wind; typically in the neck arteries (arterial tortuosity)
- Heart defects at birth (atrial septal defect, patent ductus arteriosus, bicuspid aortic valve)
Eyes, Head and Neck:
- Widely-spaced eyes (hypertelorism)
- White of the eye looks blue or gray
- Wide or split (bifid) uvula (the tissue that hangs down in the back of the throat)
- Cleft palate
- Premature fusion of skull bones (craniosynostosis)
- Instability or malformation of the spine in the neck
- Easy bruising, wide scars, soft skin texture, and translucent skin (when it looks almost see-through)
- Club foot (when the foot is turned inward and upward at birth)
- Poor mineralization of the bones (osteoporosis) that can make the bones more likely to break)
- Curvature of the spine (scoliosis)
- Chest wall protrusion or indentation (pectus deformities)
- Allergies to food and elements in the environment
- Stomach and intestine problems, such as difficulty absorbing food and chronic (comes and goes but never really goes away) diarrhea, abdominal pain, and/or gastrointestinal bleeding and inflammation
- Rupture of the spleen or bowel (rare)
- Rupture of the uterus during pregnancy (rare)
When a person has these particular features, it is important to be evaluated for Loeys-Dietz syndrome.