Loeys-Dietz syndrome

Loeys-Dietz syndrome

Loeys-Dietz syndrome (LDS) is a rare genetic condition, a heritable connective tissue disorder (HCTD) that affects the body’s connective tissues. These tissues provide structure and support to the skin, bones, blood vessels, and many organs. LDS can affect people of all ages and backgrounds.

What causes LDS?

LDS is caused by a change (known as a pathogenic variant or mutation) in one of several genes involved in a process called the TGF-beta pathway. This pathway plays a key role in cell growth and tissue repair.

There are different types of LDS, depending on which gene is affected. All types share some features, but the severity and symptoms can vary.

How is LDS inherited?

The following genes are implicated in LDS:

Notes:

• TGFBR1 and TGFBR2 were the first genes identified and remain the most commonly implicated in LDS.
• SMAD3, TGFB2, and TGFB3 represent other dominant forms, each with slightly different clinical features.
• SMAD2 is associated with LDS features but has not been formally classified into a specific LDS type.
• IPO8 is the only gene identified to cause LDS through autosomal recessive inheritance.

Most people with LDS inherit the condition in an autosomal dominant way. This means one copy of the changed gene (from either parent) is enough to cause the condition. Some rare forms are inherited in an autosomal recessive manner, which requires two copies of the changed gene.

LDS can also occur as a result of a new (de novo) genetic change with no previous family history.

What are the symptoms?

LDS affects multiple systems in the body. Not everyone with LDS will have the same symptoms, even within the same family. Common features include:

Blood vessels (vascular system):

• Aneurysms (bulging) or dissections (tears) of the aorta and other arteries
• Arterial tortuosity (twisting of blood vessels)

Bones and joints (skeletal system):

• Curved spine (scoliosis)
• Chest wall differences (pectus excavatum or carinatum)
• Joint hypermobility (loose joints) or joint contractures
• Long, slender fingers and toes (arachnodactyly)
• Clubfoot (talipes equinovarus)

Face and skull (craniofacial features):

• Wide-set eyes (hypertelorism)
• Cleft palate or a split/bifid uvula
• Skull bones that fuse too early (craniosynostosis)

Skin:

• Soft, velvety skin
• Translucent skin where veins are visible
• Easy bruising
• Fragile or stretched scarring

Other features:

• Allergies, asthma, eczema, or inflammatory bowel conditions
• Eye conditions such as strabismus (crossed eyes) or blue-tinged sclera (whites of the eyes)

How is LDS diagnosed?

Doctors may suspect LDS based on a person’s physical features and family history. A diagnosis can be confirmed with genetic testing, which looks for changes in one of the genes known to cause LDS. Heart and blood vessel scans—like echocardiograms, MRAs, or CTAs—are used to check for stretched or torn arteries (called aneurysms or dissections).

How is LDS managed?

There is no cure for LDS, but many complications can be managed with early and regular care and monitoring. Treatment is usually provided by a multidisciplinary team and may include:

• Ongoing heart and blood vessel monitoring (at least once a year)
• Medicines such as beta-blockers or angiotensin receptor blockers (ARBs) to reduce pressure on the arteries
• Surgery to repair or prevent dangerous blood vessel changes
• Management of joint or spine issues by orthopaedic specialists
• Craniofacial surgery if needed for cleft palate or skull concerns
• Allergy and immune care for inflammatory conditions
• Regular eye checks, especially for children

People with LDS are usually advised to avoid contact sports, isometric exercises, and activities that place stress on the heart or joints.

What about pregnancy?

Pregnancy can carry higher risks for people with LDS due to the chance of aortic dissection or uterine rupture. Individuals planning pregnancy should consult a clinical genetics team and be closely monitored by cardiologists and obstetricians experienced in managing heritable connective tissue conditions. More frequent heart imaging is often recommended during and after pregnancy.

Living with LDS

Living with LDS can be challenging, especially when the condition is first diagnosed. However, with early intervention, monitoring and ongoing care, many people with LDS lead fulfilling lives. Support from health professionals, patient advocacy organisations like CTDNA, and peer networks can be helpful.

A recent study found that people with LDS often develop effective coping strategies. Despite the condition’s impact on physical health and daily life, many report good emotional adjustment and quality of life.

As LDS is a Rare Disease further information in the Rare Disease Resources section of the CTDNA website may be useful. 

References

Loeys BL, Dietz HC. Loeys-Dietz Syndrome. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2025 [updated 2024 Sep 12]. Available from: [https://www.ncbi.nlm.nih.gov/books/NBK1133/pdf/Bookshelf_NBK1133.pdf]

Loeys-Dietz Syndrome Foundation. Medical Information [Internet]. Available from: [https://www.loeysdietz.org/en/medical-information]

Gouda P, Kay R, Habib M, et al. Clinical features and complications of Loeys-Dietz syndrome: A systematic review. Int J Cardiol. 2022;362:158–167.

Baeza-Velasco C, Rodriguez N, Parra L, Gutiérrez-Rosado T. Adjustment to disease and quality of life in people with vascular Ehlers-Danlos and Loeys-Dietz syndromes: A mixed-method study. Front Psychol. 2023;14:1019863.