arterial tortuosity syndrome

Arterial tortuosity syndrome (ATS) is a connective tissue condition that primarily affects the cardiovascular system, causing the large and medium-sized arteries to become elongated, twisted, and fragile. Changes in the SLC2A10 gene alter the integrity of the arterial wall, predisposing affected individuals to aneurysms, dissections, and areas of narrowing, especially in the pulmonary arteries. Signs usually appear in infancy or early childhood, although the exact age of onset can vary. ATS is considered very rare, affecting fewer than one in one million people worldwide.

Vascular changes dominate the clinical picture. Almost everyone with ATS shows pronounced tortuosity of the aorta and other major arteries, and many develop aneurysms or localized dilatation of the aortic root and carotid arteries. Pulmonary artery stenosis and episodes of congestive heart failure are frequently reported early concerns that can prompt medical evaluation. Over time, progressive arterial twisting may lead to additional areas of stenosis or dissection, so careful follow-up is important. Beyond the blood vessels, several connective-tissue features can appear: soft or thin skin that may stretch easily, joint hypermobility, and hernias such as congenital diaphragmatic or inguinal hernias. Characteristic facial findings in some children include a long face, down-slanted eye openings, a high palate, macrotia (large ears), and a convex nasal ridge. Eye findings such as astigmatism and skin telangiectasias have also been described. Not all individuals experience all features, and severity varies considerably. Some people have life-threatening vascular events in childhood, whereas others have milder courses with mainly cosmetic or orthopedic issues.

ATS results from pathogenic variants in the SLC2A10 gene, which encodes a glucose transporter thought to help maintain normal connective-tissue structure within the arterial wall. When both copies of the gene are altered, arterial elasticity is reduced, leading to elongation, tortuosity, and a tendency toward aneurysm formation. The condition is inherited in an autosomal recessive pattern. A child must receive one altered copy of SLC2A10 from each parent to be affected. Parents who each carry one altered copy (carriers) are typically healthy but have a 25 percent chance with every pregnancy of having a child with ATS, a 50 percent chance of having a carrier child, and a 25 percent chance of having a child with two normal copies. Because this condition is more common when parents share a common ancestor, carrier testing may be particularly relevant for families with shared ancestry as well as for relatives of an affected individual. Genetic counseling is strongly recommended for families to understand inheritance and reproductive options.

Currently, management focuses on supportive care and complication prevention. Long-term management includes regular surveillance for potential cardiovascular complications, typically involving periodic imaging of the aorta and major branch vessels to detect enlargement, stenosis, or dissection before they become life-threatening. Blood-pressure control, activity guidance, and prompt treatment of any detected aneurysms or narrowed vessels are individualized by the cardiology and vascular surgery teams. Because ATS affects multiple body systems, care is best coordinated through a multidisciplinary team that may include cardiologists, vascular surgeons, medical geneticists, ophthalmologists, and orthopedic specialists. Physical or occupational therapy can address joint hypermobility, and dermatologic support may help manage fragile skin. Families should work closely with their healthcare providers to determine the most appropriate monitoring intervals and interventions for their specific situation.

Outcomes for individuals with ATS depend on the severity and location of arterial involvement, as well as how early complications are detected and treated. Some people remain relatively stable with vigilant monitoring, while others experience serious vascular events that require surgical intervention. Outcomes described in medical literature continue to evolve as standards of care improve. Regular follow-up at specialized centers greatly increases the chance of identifying treatable complications early. Families often find it helpful to connect with genetic counselors and clinicians experienced in heritable vascular disorders for ongoing guidance and support.

Clinical trials are underway exploring new approaches to prevent or treat vascular complications in ATS. Individuals interested in participating can search ClinicalTrials.gov or consult their care team about eligibility.