--- title: Loeys–Dietz syndrome description: What Loeys–Dietz syndrome is, why the aorta widens and the arteries become tortuous, how the condition is detected, which treatment approaches clinical guidelines describe, and when urgent help is needed. type: disease aliases: - LDS - Loeys-Dietz syndrome - TGF-β vasculopathy sources: - tier: guideline org: aha-acc title: '2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines' year: 2022 doi: 10.1161/CIR.0000000000001106 url: https://doi.org/10.1161/CIR.0000000000001106 - tier: guideline org: esc title: 2024 ESC Guidelines for the management of peripheral arterial and aortic diseases year: 2024 doi: 10.1093/eurheartj/ehae179 url: https://doi.org/10.1093/eurheartj/ehae179 - tier: guideline org: minzdrav-rf title: Аневризмы грудной и торакоабдоминальной аорты year: 2025 url: https://cr.minzdrav.gov.ru/view-cr/919_1 - tier: reference org: msd-manuals title: Thoracic Aortic Aneurysms (MSD Manual Professional Version) year: 2024 url: https://www.msdmanuals.com/professional/cardiovascular-disorders/diseases-of-the-aorta-and-its-branches/thoracic-aortic-aneurysms - tier: reference org: msd-manuals title: Marfan Syndrome (MSD Manual Professional Version) year: 2025 url: https://www.msdmanuals.com/professional/pediatrics/connective-tissue-disorders-in-children/marfan-syndrome sources_checked: 2026-10-14 review: null --- Loeys–Dietz syndrome is an inherited disorder of connective tissue. It causes aneurysms and dissections of the aorta and its branches, tortuous (twisted) arteries, skeletal features similar to those of [Marfan syndrome](../marfan-syndrome/), and its own distinctive features of the face and skin. The main danger is an aneurysm of the root and ascending part of the aorta and [aortic dissection](../aortic-dissection/): these are the leading causes of serious complications and death in this syndrome.

The aorta begins with the root, the segment from the aortic valve annulus to the sinotubular junction; then come the ascending aorta, the arch with the arteries that branch off it, and the descending thoracic aorta. In the diagram the aorta is not widened anywhere, and the arch branches are drawn straight for simplicity.

In Loeys–Dietz syndrome the root and the ascending aorta are the parts that widen most often. The branches of the aorta can be tortuous, so doctors examine the whole aorta and its branches; in the diagram the tortuosity is shown, as an illustration, on the arch branches.

After a planned operation the root and the whole ascending aorta have been replaced with a graft: this operation is done to prevent type A aortic dissection. The patient's own aortic valve is preserved when possible, and replaced as well when it cannot be; the surgeon chooses the type of operation. The arch, the descending aorta and the branches stay as they were: in this syndrome aneurysms and dissection can develop in them too, so monitoring of the aorta continues after the operation.

## Why it happens The syndrome is caused by changes (pathogenic variants) in one of five genes: TGFBR1, TGFBR2, SMAD3, TGFB2 or TGFB3. Sometimes these changes affect the aorta with few outward signs of the condition. The syndrome is inherited: a child of a person with Loeys–Dietz syndrome has a 50% chance of inheriting the changed gene. Even within one family, the aortic disease can vary greatly. Loeys–Dietz syndrome is inherited in an autosomal dominant pattern; together with Marfan syndrome and [vascular Ehlers–Danlos syndrome](../vascular-ehlers-danlos-syndrome/) it is classed as a syndromic heritable thoracic aortic disease (HTAD). The disease caused by variants in these five genes is also termed transforming growth factor-β (TGF-β) vasculopathy. Congenital connective tissue disorders, including this syndrome, cause cystic medial necrosis, a degeneration of the middle layer of the aortic wall that leads to [thoracic aortic aneurysms](../thoracic-aortic-aneurysm/). In these conditions, aneurysms of the aortic root and ascending aorta develop at an early age and grow faster than sporadic aneurysms. Most information is available for TGFBR1 and TGFBR2 variants: with them, type A dissection may occur at a younger age and at a smaller aortic root diameter than in Marfan syndrome. SMAD3 variants may lead to dissection at variable aortic diameters and are associated with premature osteoarthritis and a later onset of aortic disease. Based on limited data, aortic disease with TGFB2 and TGFB3 variants may be less aggressive. ## Symptoms A widened aorta may cause no symptoms for a long time: most thoracic aortic aneurysms cause none until complications develop. In this syndrome aneurysms occur not only in the root and ascending aorta, but also in the arch, the descending and [abdominal aorta](../abdominal-aortic-aneurysm/), the branches of the aorta and the blood vessels of the brain. The most dangerous complication is aortic dissection. Features outside the blood vessels help raise suspicion of the syndrome, although they differ between the genes: early fusion of the skull sutures (craniosynostosis), widely spaced eyes, bluish whites of the eyes, a split or broad uvula (the small fleshy tag at the back of the soft palate), translucent skin with visible veins, and club foot. With variants in the SMAD3 gene, osteoarthritis develops early. In the heart, [mitral valve prolapse](../mitral-valve-prolapse/) may occur. A [bicuspid aortic valve](../bicuspid-aortic-valve/) is more common in this syndrome than usual: it is found in about 10% of patients. The ACC/AHA table of features also lists hypertelorism and dural ectasia, and, with SMAD3 variants, premature osteoarthritis and peripheral neuropathy. With TGFBR1 and TGFBR2 variants, severe extra-aortic features (craniosynostosis, cleft palate, hypertelorism, bifid uvula, marked arterial tortuosity, wide scars, translucent skin) are regarded as features associated with a higher risk of dissection. In a series of 90 patients with TGFBR1 and TGFBR2 variants, aneurysm disease involved the ascending aorta in 78%, the arch in 10%, the descending aorta in 10%, the abdominal aorta and its branches in 17%, the thoracic aortic branches in 21% and the head and neck arterial branches in 10%. Cerebral aneurysms are described in 10–18% of patients. In patients with an aneurysm or a previous dissection, the arteries may enlarge relatively rapidly. ## How it is diagnosed Signs that point to an inherited aortic disease include features of Marfan, Loeys–Dietz or vascular Ehlers–Danlos syndrome, thoracic aortic disease before the age of 60, aneurysms of the aorta or other arteries in close relatives, and unexplained sudden death of a relative at a relatively young age. If such signs are present in a person with an aneurysm of the aortic root or ascending aorta, or with a thoracic aortic dissection, genetic counselling at an experienced centre and, if needed, a genetic test are recommended. If a changed gene is found, testing of blood relatives who may carry it is recommended, whatever their age. The size of the aortic root and ascending aorta is usually measured with a [heart ultrasound (echocardiography)](../../diagnostic/echocardiography/), which also detects a bicuspid aortic valve. At the first evaluation, the whole aorta and its branches from head to pelvis are examined with CT or MRI to look for aneurysms, dissections and arterial tortuosity. After that the aorta is checked regularly; how often is decided by the doctor, based on its size and how fast it grows. Assessment in a centre experienced in inherited aortic disease is recommended. Loeys–Dietz syndrome is part of the differential diagnosis of Marfan syndrome. In patients who meet the clinical criteria for Marfan syndrome but do not have ectopia lentis, genetic testing helps exclude Loeys–Dietz syndrome. Gene panels for heritable thoracic aortic disease include the 11 genes confirmed to confer a highly penetrant risk, among them TGFBR1, TGFBR2, SMAD3 and TGFB2. ESC suggests that management be guided by the underlying gene and variant. All the genes of the syndrome confer a risk of aortic involvement beyond the root, as well as of branch vessel and intracranial aneurysms, so echocardiography alone is not enough. ## How it is treated Management includes medicines, lifestyle changes, regular imaging of the aorta and surgery. Treatment is tailored to each person and decided together with them. Medicines are prescribed to reduce the stress that the blood flow puts on the aortic wall; which medicines are needed is decided by the doctor. With significant aortic disease, lifting heavy weights while straining, sudden maximal efforts and collision sports are discouraged. When the aortic root and ascending aorta widen, a planned operation is done before a dissection happens: the root and the whole ascending aorta are replaced with a graft. This operation prevents type A dissection and improves outcomes. When to operate is decided together with the patient, taking into account the gene, the size of the aorta and how fast it grows, features outside the aorta, dissections in relatives, age and sex. If the anatomy of the valve allows it and an experienced surgeon is available, the patient's own aortic valve is preserved. There is little information on the size of the arch, descending and abdominal aorta at which a planned operation is needed. After a dissection the aorta often keeps widening, and repeat operations are frequently needed. Aortic dissections during pregnancy have been described in women with TGFBR1 or TGFBR2 variants. For this reason, before pregnancy, genetic counselling, a discussion of the risk of aortic dissection during pregnancy, and imaging of the aorta to know its size are recommended. There are no randomised trials of medicines to reduce aortic growth or the risk of dissection in Loeys–Dietz syndrome; the approach to medical therapy is carried over from Marfan syndrome, based on the similarities between the two conditions and on data from mouse models. The ACC/AHA and Russian Ministry of Health guidelines recommend that the threshold for prophylactic replacement of the aortic root and ascending aorta be informed by the specific genetic variant, and ACC/AHA add the aortic diameter and growth rate, extra-aortic features, family history, patient age and sex, and physician and patient preferences. ESC allows the surgical threshold to be adjusted according to the underlying gene, taking associated risk features into account. At the time of root replacement the entire ascending aorta is also replaced, because aneurysm and dissection of its distal part may occur after isolated root replacement. For dilation of the sinuses and tubular ascending aorta in these syndromes, the Russian Ministry of Health guideline names root replacement with reimplantation of the aortic valve (the David procedure), or, when that is not possible, the Bentall–De Bono procedure. In Marfan syndrome, Loeys–Dietz syndrome and vascular Ehlers–Danlos syndrome, open repair rather than endovascular repair is recommended for an intact thoracoabdominal aortic aneurysm that requires intervention. ## When to call an ambulance Aortic dissection is one of the leading causes of death in Loeys–Dietz syndrome, and a dissection or a suspected dissection needs emergency hospital admission. Call your local emergency number (112 in the EU, 911 in the US and Canada, 999 in the UK) for sudden, severe pain in the chest or back (sometimes in the abdomen), especially if it is worst at the very start. The pain is not necessarily "tearing": more often it is described as sharp or stabbing. Also call an ambulance for signs of a stroke or sudden paralysis of the legs. If a person with known thoracic aortic disease develops new symptoms or their symptoms get worse, emergency hospital admission is also needed. More about the warning signs is in the article on [aortic dissection](../aortic-dissection/). As with any disease of the heart and blood vessels, call an ambulance for fainting, chest pain or severe shortness of breath: this is the site's general safety rule, repeated at the bottom of every page.