Loeys-Dietz syndrome: causes, aortic surveillance and living with the condition

Connective tissue supports many parts of the body: the walls of blood vessels, the ligaments that hold bones together, the skin and internal organs. In Loeys-Dietz syndrome (LDS) this tissue is not assembled correctly because of a change in one of several genes. The Leeds Teaching Hospitals leaflet, written by clinical genetics, explains that this weaker connective tissue can cause changes in the blood vessels, heart, skin, joints, intestines and uterus.

LDS belongs to the same wider family as Marfan syndrome. The Marfan Trust, a UK charity that now supports people with both conditions, describes them as connective tissue 'cousins' and notes that several people have been diagnosed with one only to find they have the other. It compares them in a table: Marfan syndrome is caused by changes in the FBN1 gene and LDS by changes in several genes, and LDS is much rarer.

The Leeds leaflet says people with LDS can have widening of the arteries, including the aorta; bendy or twisty blood vessels (arterial tortuosity); differences in the head and face, such as widely spaced eyes and a split or wide uvula; skeletal changes such as long fingers, a chest wall that sinks in or sticks out, or curvature of the spine; and skin and joint changes such as flexible joints, joint pain or very soft skin. Not everyone has all of these features and the condition is very variable, even within a family.

The leaflet describes several problems that can arise. They are summarised in the table.

If LDS is suspected, a genetic test may be carried out to look for a change in one of the associated genes. The Leeds leaflet points out that it is not always possible to find a gene change, even in someone with many features of LDS, because not everything is yet known about the genes involved. The Marfan Trust adds that knowing the correct diagnosis depends on finding the gene change, that LDS can present earlier than Marfan syndrome, and that doctors need to know the cause to choose the best treatment.

In most cases, according to the Leeds leaflet, the change arises for the first time in the person affected (3 in 4 cases); in 1 in 4 it has been inherited. LDS follows dominant inheritance, so someone with LDS has a 50% chance of passing it to each child. For people planning a family there may be options for testing a pregnancy or for preimplantation genetic testing with IVF. Where someone is diagnosed, first-degree relatives (parents, siblings and children) are recommended to be offered testing.

The Leeds leaflet recommends regular ultrasound scans of the heart (echocardiograms) or other imaging of the aorta by a specialist cardiologist, a whole-body MRI angiogram to look for tortuosity or aneurysms, and flexion and extension X-rays of the neck bones. If the aorta is dilated this can be managed with medication or sometimes surgery. People may be advised to have a neck X-ray before any operation to check the bones are in line, and some need surgery to fix unstable neck bones in place.

Other care is directed at the specific problem: repair of a large cleft palate if it makes feeding difficult, monitoring of skull shape in babies with craniosynostosis, standard treatment of allergies, and measures to manage joint and muscle pain.

The Leeds leaflet explains that pregnancy makes connective tissue more stretchy and puts the body under stress. In LDS it can make aneurysms develop more quickly, and there is a risk of the womb muscle tearing as the pregnancy grows (uterine rupture), which can be life threatening to the mother and pregnancy. Pregnant women with LDS should be monitored by a specialist and have extra heart and blood vessel scans during pregnancy. Anyone with LDS who is thinking about pregnancy should ask for specialist pre-conception advice rather than waiting until they are pregnant.

Because the condition is variable and rare, many people find that most of their care is coordinated between a clinical genetics service and a cardiology team that knows connective tissue conditions. The Marfan Trust supports patients and families with LDS and provides educational material, and the Leeds leaflet notes that American organisations such as the Marfan Foundation and Loeys-Dietz Syndrome Foundation are open to anyone, but warns that some recommendations might differ for people in the UK under the NHS.

Seek urgent help by calling 999 for sudden severe chest, back or abdominal pain, or sudden severe headache, in anyone with a known aortic or arterial condition, as these can signal a tear or rupture.

Genetic testing, aortic imaging and specialist cardiology for LDS are normally provided through NHS clinical genetics and cardiology services, and the family testing pathway runs through the same teams. Private genetic tests and scans are available but only help if the results reach the team that will manage your long-term surveillance.