Loeys-Dietz Syndrome

Loeys-Dietz syndrome (LDS) is a connective tissue disorder characterized by the following medical characteristics:

Aneurysms (widening or dilation) of the arteries: Enlargement is most often observed in the aortic root (base of the artery leading from the heart), but can be seen in other arteries throughout the body

Arterial tortuosity (twisting or spiraled arteries): This is most often seen in the vessels of the neck

Hypertelorism (widely-spaced eyes)

Bifid (spilt) or broad uvula (the little piece of flesh that hangs down in the back of the mouth)

A variety of other craniofacial, skeletal, skin and cardiac findings have also been described. Following is a list of some other characteristics that observed together, may be suggestive of a diagnosis of LDS.

• Craniosynostosis (early fusion of the skull bones)
• Blue sclerae (blue tinge to the whites of the eyes)

• Clubfoot
• Scoliosis (s-like curvature of the spine)
• Cervical-spine instability (instability in the vertebrae directly below the skull)
• Joint laxity
• Pectus excavatum (chest wall deformity that cause the sternum and breast bone to grow inward) / Pectuas carinatum (chest wall deformity that pushes the sternum and breast bone out)

• Translucent
• Soft or velvety skin
• Easy bruising
• Abnormal or wide scarring
• Soft skin texture
• Hernias

Additionally, congenital (existing at birth) heart defects, which can include patent ductus arteriosus (PDA), atrial or ventricular septal defect (ASD/VSD) and bicuspid aortic valve (BAV).

A subgroup of individuals with LDS have also been shown to have food allergies (sometimes severe) and gastrointestinal diagnoses including irritable bowel disease and Crohn’s disease.

WHAT DO I DO IF I’M SUSPICOUS OF LDS IN MYSELF OR A FAMILY MEMBER?

People with LDS features need to see a geneticist or cardiologist who knows about LDS to obtain appropriate screening and genetic testing. It is important that people with LDS get an early and correct diagnosis so they can receive the right treatment. 

The geneticist or cardiologist may decide to obtain vascular imaging to get more information about the aorta and other arteries. This will include an echocardiogram (ultrasound of the heart) and may also include CT or MRI imaging with contrast of the entire vasculature (head, neck, chest, abdomen, pelvis).

Genetic testing is available to confirm a diagnosis of LDS.

THE GENETICS OF LDS

LDS exhibits an autosomal dominant inheritance pattern, which means that when an individual has been diagnosed with LDS, each of their offspring (regardless of number and/or sex of offspring) 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. 

TREATMENT OF LDS

LDS manifests itself in a number of ways; therefore, no two persons with LDS will have identical medical characteristics. However, there are some general guidelines of the type of imaging that needs to be performed. Timing of follow-up imaging is determined on a case-by-case basis.

Cardiovascular Management:

• Pressure on the aorta is typically controlled by administration of medications such as beta-blockers or angiotensin receptor blockers that work to lessen the strain on the body’s major arteries by reducing heart rate and blood pressure.
• Continued monitoring of the aorta and other arteries through echocardiograms, CTs or MRIs with contrast of the head through pelvis to detect and monitor aneurysms.
• Vascular surgery is a widely recommended treatment option as a preventative surgery for individuals with a rapidly enlarging aorta or a  pronounced family history of arterial dissection. Aortic root replacement is the most common vascular surgery occurring in individuals with LDS and is highly successful.
• Exercise restrictions are typically put in place to assist in slowing the rate of aortic and arterial aneurysm growth. It is advised that individuals with LDS avoid competitive sports, especially contact sports and other exercises or muscle straining activities performed to the point of exhaustion. 

Skeleton:

• X-rays of the cervical spine in the flexion and extension positions is performed to assess for vertebral anomalies and/or instability.  Rarely, surgery for cervical spine fusion is required.
• Individuals with LDS may need orthopedic surgery or other interventions such as bracing for scoliosis, orthotics/surgeries for foot deformities, and harnesses for congenital hip dislocation.

Gastrointestinal Complications:

• Some individuals need to work closely with a gastroenterologist to eliminate foods that cause inflammation of the bowel and for medications that may be helpful. In rare cases, intervention includes placement of a G-tube (gastrostomy tube) to help individuals get proper nutrition.

To learn more about Loeys-Dietz syndrome, please visit the Loeys-Dietz Syndrome Foundation website.

Additionally, GeneReviews can be useful in learning more about LDS.